biotechnology research projects 2016

Research Projects 2016

BIOTECHNOLOGY

School of Chemistry & Molecular BiosciencesFaculty of Science

Honours

Graduate DiplomaMasters

Masters Res ExProfessional Doctorate

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CONTENTS

INDUSTRY PROJECTS Industry Contributors Organisation/Business Unit Page No. Professor Ross Barnard Director, Biotechnology Program

School of Chemistry & Molecular Biosciences 4

Professor Peter Gray Australian Institute for Bioengineering and Nanotechnology (AIBN)

5

Associate Professor Peer Schenk School of Biological Sciences 6 Professor Istvan Toth School of Chemistry & Molecular Biosciences /

TETRAQ 7

Professor Matt Trau Australian Institute for Bioengineering and Nanotechnology (AIBN) / School of Chemistry & Molecular Biosciences

8

Advanced Water Management Centre Dr Phil Bond Dr Liu Ye Professor Zhiguo Yuan Dr Bernadino Virdis Dr Damien Batstone Dr Jelena Radjenovic Dr Maria Jose Farre Dr Jens Kroemer

9

Cook Australia Pty Ltd 10

QAAFI Dr Ala Lew-Tabor Dr Manuel Rodriguez Valle Dr Jess Morgan

Queensland Alliance for Agriculture & Food Innovation (Centre for Animal Science)

11

Dr Neena Mitter Queensland Alliance for Agricultural and Food Innovation (QAAFI)

12

Sirromet Wines Ms Jessica Ferguson Mr Adam Chapman

Sirromet Wines 13

Dr Linda Lua Australian Institute for Bioengineering and Nanotechnology (AIBN)

14

Associate Professor Craig Williams School of Chemistry & Molecular Biosciences 15

GROUP PROFILES Group Name and Contributors Organisation/Business Unit Page No. Centre for Nutrition and Food Sciences

Dr Eugeni Roura Dr Nadia de Jager

Centre for Nutrition and Food Sciences (CNAFS)

16

Diamantina Institute for Cancer, Immunology & Metabolic Medicine

Professor Ranjeny Thomas Dr Raymond Steptoe

Diamantina Institute for Cancer, Immunology & Metabolic Medicine

17

Mater Medical Research Institute Dr David Munster Dr Kristen Radford

Mater Medical Research Institute (MMRI)

18-19

Polymer Chemistry Group Professor Andrew Whittaker

Centre for Magnetic Resonance Australian Institute for Bioengineering and Nanotechnology (AIBN)

20

Professor Matt Trau Dr Ashley Connolly

Australian Institute for Bioengineering and Nanotechnology (AIBN) / School of Chemistry & Molecular Biosciences

21

Professor Matt Trau Dr Muhammad Shiddiky

Australian Institute for Bioengineering and Nanotechnology (AIBN) / School of Chemistry & Molecular Biosciences

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INDIVIDUAL CONTRIBUTORS

Individual Contributors Organisation/Business Unit Page No. Dr Sassan Asgari School of Biological Sciences 23 Dr Andrew C. Barnes Centre for Marine Studies 24 Dr Christine Beveridge Centre for Integrative Legume Research 25 Associate Professor Joanne Blanchfield School of Chemistry & Molecular Biosciences 26 Professor Jimmy Botella School of Biological Sciences 27 Professor Paul Burn Centre for Organic Photonics & Electronics

(School of Chemistry & Molecular Biosciences) 28

Professor Rob Capon Institute for Molecular Bioscience 29 Professor Bernie Carroll School of Chemistry & Molecular Biosciences 30 Dr Marina Chavchich Australian Army Malaria Institute 31 Professor David Craik Institute for Molecular Bioscience 32 Professor James De Voss School of Chemistry & Molecular Biosciences 33 Dr Annette Dexter Australian Institute for Bioengineering &

Nanotechnology (AIBN) 34

Associate Professor Paul Ebert School of Biological Sciences School of Chemistry & Molecular Biosciences

35

Dr Darryl Eyles Queensland Brain Institute 36 Professor David Fairlie Institute for Molecular Bioscience 37 Associate Professor Camile Farah School of Dentistry / UQ Centre for Cancer

Research 38

Associate Professor Vito Ferro Deputy Director, Biotechnology Program School of Chemistry & Molecular Biosciences

39

Dr Donald Gardiner CSIRO Plant Industry/Queensland BioScience Precinct, UQ-St. Lucia Campus

40

Professor Ian Gentle School of Chemistry & Molecular Biosciences ARC Centre for Functional Nanomaterials

41

Professor Robert G Gilbert Centre for Nutrition & Food Sciences School of Chemistry & Molecular Biosciences

42

Professor Elizabeth Gillam School of Chemistry & Molecular Biosciences 43 Professor Jeff Gorman Queensland Institute of Medical Research (QIMR) 44 Professor Peter Gresshoff Centre for Integrative Legume Research 45 Dr Ulrike Kappler School of Chemistry & Molecular Biosciences 46 Professor Mark Kendall Dr Simon Corrie

Australian Institute for Bioengineering & Nanotechnology (AIBN)

47

Professor Alexander Khromykh School of Chemistry & Molecular Biosciences 48 Professor Glenn King Institute for Molecular Bioscience 49 Professor Bostjan Kobe School of Chemistry & Molecular Biosciences 50 Dr Shih-Chun Lo (Lawrence) Centre for Organic Photonics & Electronics

School of Chemistry & Molecular Biosciences 51

Dr Patricia Lopez-Sanchez Centre for Nutrition and Food Science ARC Centre for Excellence in Plant Cell Walls

52

Professor Alan E. Mark School of Chemistry & Molecular Biosciences 53 Professor Daniel Markovich School of Biomedical Sciences 54 Associate Professor Fred Meunier Queensland Brain Institute / School of Biomedical

Sciences 55

Associate Professor Chamindie Punyadeera School of Biomedical Sciences Institute of Health and Biomedical Innovations

56

Queensland University of Technology Dr Steven Reid Deputy Director, Biotechnology Program

School of Chemistry & Molecular Biosciences Group Leader AIBN

57

Associate Professor Joe Rothnagel School of Chemistry & Molecular Biosciences 58 Associate Professor Mark Schembri School of Chemistry & Molecular Biosciences 59 Dr Horst Joachim Schirra School of Chemistry & Molecular Biosciences 60 Dr Benjamin Schulz School of Chemistry & Molecular Biosciences 61 Associate Professor Conrad Sernia School of Biomedical Sciences 62 Dr Yasmina Sultanbawa Queensland Alliance for Agriculture and Food

Innovation (QAAFI) 63

Dr Kate Stacey School of Chemistry & Molecular Biosciences 64 Dr Matt Sweet Institute for Molecular Bioscience 65 Professor Stephen Taylor School of Biomedical Sciences 66 Dr Hang Ta Australian Institute for Bioengineering &

Nanotechnology (AIBN) 67

Dr Simon Worrall School of Chemistry & Molecular Biosciences 68 Professor Paul Young School of Chemistry & Molecular Biosciences 69 Dr Adrian WIegmans Queensland Institute of Medical Research (QIMR) 70

Dr Stefano Freguia Centre for Microbial Electrosynthesis Advanced Water Management Centre

71

Professor Richard Lewis Chemistry and Structural Biology Division Centre for Pain Research

72

Dr Zyta Ziora Institute for Molecular Bioscience 73

QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI)

Dr Femi Akinsanmi/A.Prof. Andre Drenth QAAFI (Ecosciences Precinct, Boggo Road, Dutton Park)

75

Dr Femi Akinsanmi QAAFI (Ecosciences Precinct, Boggo Road, Dutton Park)

76

Dr Femi Akinsanmi/Dr Bruce Topp QAAFI (Ecosciences Precinct, Boggo Road, Dutton Park)

77

Dr Karine Chenu QAAFI (Toowoomba-Gatton) 78 Associate Professor Ralf Dietzgen Dr Paul Scott Professor Peter Gresshoff

CILR, John Hines Building and QAAFI, Ritchie Bldg, UQ St Lucia Campus

79

Associate Professor Ralf Dietzgen

QAAFI Ritchie Laboratories, St. Lucia Campus

80

Dr Andrew Geering Professor John Thomas

QAAFI (Ecosciences Precinct, Boggo Road, Dutton Park)

81

Dr Jim Hanan Biological Information Technology Group 82 Associate Professor Elizabeth Aitken Dr Lee Hickey

School of Agriculture and Food Sciences St Lucia campus, The University of Queensland

83

Associate Professor Athol Klieve Dr Justin Gibson

BAgSc MRurSc PhD MASM, UQ Gatton campus or ESP, Dutton Park BVSc PhD

84

Dr Mary Fletcher Health and Food Sciences Precinct, Coopers Plains

85

Dr Manuel Rodriguez Valle Dr Ala Lew-Tabor

Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.

86

Dr Manuel Rodriguez Valle Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.

87

Dr Sushil Dhital Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.

88

SCMB Biotechnology Research Projects 2016 | Industry Project

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INDUSTRY PROJECTS

Would you like to undertake part of your research project in a company outside UQ?

Experience a commercial workplace

• Make contacts to help you with your career • Receive support and guidance from UQ as well as your industry supervisor

Opportunities exist in these industries and more:

• biotechnology • chemical • pharmaceutical • food processing • pathology

As a Biotechnology, Chemistry or Molecular Biosciences student, you may be able to undertake a research project or internship with companies with whom SCMB already has a working relationship. In addition, if there is a particular company you would like to work with, you are welcome to propose it to us. In 2014, SCMB students have been hosts for a variety of industry projects at the following companies:

• Anteo Diagnostics • Patheon Biologics • Mars Petcare (Albury-Wodonga) • Ellume • Olayan (Saudi Arabia) • QFAB • Cook Medical


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Summer project benefits student and Biotechnology company Van Mai was inspired by a lecture i n t h e b i o t e c h n o l o g y p r o g r a m , to do an industry placement internship that led to her work being incorporated into presentations to customers by a successful Brisbane biotech company. “Two scientists from Anteo Diagnostics gave a guest lecture in the second year Issues in Biotechnology course I was taking,” she said. “I found it very interesting and thought provoking.” Course coordinator, Associate Professor Vito Ferro,

mentioned to students that an eight-week internship at Anteo was available for a student taking the course Biotechnology Industry Placement over the summer semester. Van applied and was chosen. After two weeks of on-site training about company policy, equipment use, experiment design and record-keeping, Van felt well-equipped to undertake six weeks in the company laboratory. “I worked with one of Anteo’s signature products, Mix&Go, a high performance substance for surface coating,” said Van. “The product enables fragile biomolecules to correctly orientate and attach to a wide range of surfaces. “Specifically, I worked on optimising protocols for plate-based enzyme linked immunosorbent assays.”

Shaun Cooper of Anteo Diagnostics supervised Van’s project and said that Van was asked to use the underlying theory of Anteo’s novel ligand-metal coordination chemistry to determine its utility in improving sensitivity of an immunoassay in a format were low surface area traditionally limits performance. “Van identified the performance differences of the product in high and low surface area plate formats,” he said. “Her data demonstrated that sensitivity differences can be observed with the application of Mix&Go and that improvements are greater in the lower surface area format.

“Some of her data was incorporated into technology overview presentations given by the company’s chief scientific officer to prospective customers and partners.” Van said that the work environment at Anteo was warm and welcoming and that the experience had taught her about the business side of scientific research, including policy, protocols and the importance of discussion and collaboration. “It has also built my confidence,” she said. Van is an international student who won a scholarship from the Vietnamese government to study in Australia. She was awarded Dean’s Commendations for high achievement in her undergraduate studies, worked as a peer tutor and charity volunteer, and is now completing her Honours year in materials chemistry. She praised the quality of UQ’s teaching and learning, the range of courses, lab facilities and the beautiful St Lucia campus. Anteo Diagnostics has hosted a number of UQ biotechnology students and is keen to host more. “Students who undertake internships like Van’s gain not only general workplace skills, but also some insight into how Australian research contributes to commercial product realisation,” said Mr Cooper. “Support for translational research is currently a topic of government policy debate, and projects like Van’s are a good example of the interface between research and commercialisation.


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PROFESSOR ROSS BARNARD Director, Biotechnology Program School of Chemistry & Molecular Biosciences Phone: 07 3365 4612 Email: [email protected]

Teaching and other interests: •Biotechnology Program Director •PhD and Honours supervisor •Real-time PCR, Infectious disease diagnosis, Antibody engineering General Research Outline •Development of novel diagnostic technologies. •Antibody engineering/phage display/for cancer therapy or infectious disease diagnostics. Current research projects 1.Infectious disease diagnostic development with a focus on Campylobacter, Flaviviruses and banana viruses 2.Novel real-time PCR detection technology. 3.Antibody engineering for infectious disease diagnosis and cancer treatment. 4.Project 4 – Anti-inflammatory effects of transdermal metal ion absorption. My current research projects involve collaboration with: • Project 1 – Department of Fisheries and Forestry/QAAFI. • Project 3 – UQ Mater Institute and Pharmacy Australia Centre of Excellence • Project 4 – Therapeutics Research Unit, UQ Department of Medicine, Princess Alexandra Hospital Selected Recent Publications: Lai, R., Liang, F., Pearson,D., Barnett, G., Whiley, D., Sloots, T., Barnard, R.T., Corrie, S.R. (2012) PrimRglo: a multiplexable quantitative real time PCR system for nucleic acid detection. Analytical Biochemistry doi:10.1016/j.ab.2011.12.038 Luke R. Le Grand, Michaela White, Evan B. Siegel, and Ross T. Barnard (2012) Recombinant Vaccines: Development, Production, and Application. In: Kayser, O., Warzecha, H. eds. Pharmaceutical Biotechnology 2nd ed. Wiley-Blackwell. Barnard, R.T., Hall, R.A. & Gould E.A. (2011) Expecting the unexpected: nucleic acid-based diagnosis and discovery of emerging viruses. Expert Rev. Mol. Diagn. 11(4) 409-423 Barnard, R.T. (2010) Recombinant Vaccines Expert Rev.Vaccines 9(5), 461–463 Macdonald, J., Poidinger, M., Mackenzie, J.S., Russell, R.C., Doggett, S., Broom, A.K., Phillips, D., Potamski, J.,Gard, G., Whelan, P., Weir, R., Young, P.R., Gendle, D., Maher, S., Barnard, R.T. & Hall, R.A. (2010) Molecular phylogeny of Edge Hill Virus supports its position in the Yellow Fever Virus group and identifies a new genetic variant. Evolutionary Bioinformatics 6, 91-96 Liang, F., Lai, R., Arora, N., Zhang, K.L., Yeh , C-C., Graeme R. Barnett, G.R., Voigt, P., Corrie, S.R., Barnard, R.T. (2013) Multiplex–microsphere–quantitative polymerase chain reaction: Nucleic acid amplification and detection on microspheres. Analytical Biochemistry 432, 23–30. Chandrasekaran, N.C., Weir, C., Alfraji, S., Grice, J., Roberts, M.S. & Barnard, R.T. (2014) Effects of magnesium deficiency-more than skin deep. Exp. Biol. Med. Doi:10.1177/1535370214537745

mailto:[email protected]


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PROFESSOR PETER GRAY Australian Institute for Bioengineering and Nanotechnology (AIBN) Phone: 07 3346 3899 Email: [email protected]

Biopharmaceuticals and mammalian cell culture based biotechnology The acceptance of biopharmaceuticals as human therapeutics has been rapid, with global sales of such products now exceeding $US100 billion per annum. These sales are now growing at over 20% per annum, and there are many new biopharmaceuticals making up the potential product ‘pipelines’ of biotech and pharma companies. Of particular note is the rapid acceptance of human and humanised monoclonal antibodies as therapeutic agents. Antibodies, and the majority of other biopharmaceuticals, are large complex proteins that have to be produced by mammalian cell culture in order to have the correct post-translational modification they require for full biological activity. The Gray Lab is focused on engineering mammalian cells in order to improve their efficiency and utility in the production of complex proteins. The approaches used to gain greater understanding of such systems are also being applied to even more complex cells, viz the development of bioprocesses based on embryonic stem cells. Many of our research projects are collaborative, and often involve interactions with international biotech and pharma companies. Examples of available projects are: 1. Developing transient protein expression systems which will allow researchers to rapidly produce larger amounts of protein needed for initial characterisation and testing. 2. Developing high throughput approaches which allow the rapid selection of clones which stably express high levels of the desired biopharmaceutical. 3. Using modern ‘omics’ approaches to gain better understanding of cellular metabolism which will allow maximal protein expression by mammalian cell cultures. 4. Development of novel therapeutic antibodies. A drug discovery program in this area aims to develop novel therapeutic monoclonal antibodies for infectious diseases. The drugs will be used for treatment of severe infections caused by antibiotic resistant bacteria. The discovery program aims to create antibody molecules that can be engineered for targeted delivery of polymer-based nanoparticles as well as other novel drugs.



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PROFESSOR PEER SCHENK School of Biological Sciences Phone: 07 3365 8817 Email: [email protected]

Plant and Microbial Biotechnology, Plant-Microbe Interactions, Functional Genomics & MetaTranscriptomics, Sustainable Biofuel Production. Microalgae Biotechnology The Plant-Microbe Interaction Group specialises in the discovery of interesting new genes from plants and microorganisms (www.plantsandmicrobes.com; www.algaebiotech.org) Disease resistant plants: We use a Functional Genomics and Biodiscovery approach to study beneficial and parasitic interactions of plants with microbes. Arabidopsis is used as a model plant to study signalling pathways that enable plants to withstand pathogen attack or severe drought. The up- or down-regulation of specific key regulatory genes has led to disease resistance and drought tolerance, and this strategy is used to improve crop species. Microbial communities associated with plants: We are using molecular profiling tools, such as functional gene microarrays and 454 sequencing, to characterise highly diverse microbial communities that are associated with plants to identify novel compounds for pharmaceutical and agricultural applications. This environmental transcriptomics (metatranscriptomics) approach captures microbial activity profiles with direct implications for crop cultivation (e.g. soil-borne diseases, greenhouse gas emmissions, yield increase or decline). Biofuel production from algae: We use microalgae strains that are highly efficient producers of hydrogen or biodiesel and further optimise these by using cutting-edge molecular biology and engineering tools. Microalgae are likely the only renewable source of fuel that could match our current and future demand without competing for arable land and food production. Recently, we have developed large-scale microalgae cultivation systems to produce biofuels (biodiesel), protein-rich animal feed and Omega-3 fatty acids. This project is receiving a lot of interest from industry Projects: 1. Increased disease resistance in plants 2. Plant cell signalling in response to beneficial microbes and plant pathogens 3. Metatranscriptomics of highly diverse microbial communities 4. Biodiesel, omega-3 fatty acids and animal feed from microalgae Selected Recent Publications: 1. Çevik et al. (2012) MED25 acts as an integrative hub for the regulation of jasmonate-responsive gene expression in Arabidopsis. Plant Physiology doi: http://dx.doi.org/10.1104/pp.112.202697 2. Adarme-Vega et al. (2012) Microalgal biofactories: A promising approach towards sustainable omega-3 fatty acid production. Microbial Cell Factories 11:96. 3. Lim et al. (2012) Isolation and evaluation of oil-producing microalgae from subtropical coastal and brackish waters. PLoS ONE 7:e40751 4. Schenk et al. (2011) Unravelling plant-microbe interactions: can multi-species transcriptomics help? Trends in Biotechnology 30:177-184


http://www.algaebiotech.org/


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PROFESSOR ISTVAN TOTH School of Chemistry & Molecular Biosciences Phone: 07 3346 9892 Email: [email protected]

Drug and Vaccine Delivery: Many peptides have been identified as potential new drugs or vaccines, but few have progressed into the clinic. This is predominantly due to their rapid enzymatic breakdown, problematic delivery, and/or poor inherent immunogenicity. There is a strong need for new delivery systems that overcome these issues. Project One: Lipid-Core Peptide (LCP) delivery systems: We have previously developed a lipid-core peptide delivery system that is applicable to the delivery of a wide range of peptides. The LCP system can be optimized to improve the absorption and stability of the peptide. An advantage of the LCP system for vaccine delivery is that the antigen, carrier, and adjuvant can be included in a single chimeric molecule. Models under investigation for the use of the LCP system include vaccines against malaria, hookworm, group A streptococcus, and cancer. Further structure-activity studies are required to optimize the delivery system and to identify the mechanism of action of the delivered peptides on the host immune response. Aim: to perform structure-activity studies to further optimize the LCP delivery system. Project Two: Chemo-enzymatic synthesis of drug/vaccine delivery systems: This project aims to address shortcomings in peptide delivery by coupling naturally occurring sugars and lipids to the peptides of interest using a combination of organic synthesis and enzymatic transformations. This multidisciplinary approach (chemistry, biotechnology, biology) has the potential to not only improve peptide absorption and metabolic stability, but to enhance the access of peptides to target sites using carbohydrate and/or amino acid transport systems. The combination of chemical and enzymatic synthesis provides access to complex carbohydrate structures that can be used to target drug molecules. One example is the use of glycosyltransferases from Neisseria meningitidis to target Leu-enkephalin peptide derivatives (potential pain drug candidates) to opioid receptors in the central nervous system. Aim: to design and develop a generally applicable, novel drug delivery system (synthesized chemically and chemo-enzymatically) that targets specific cell types. Project Three: Nanovaccine delivery systems: Recent developments in nanomedicine/vaccinology have identified that the size and morphological characteristics of nanoparticle vaccines affect their efficacy. Preliminary investigations have demonstrated that 20 nm nanoparticles displaying peptide epitopes on their surface were able to induce very strong immune responses against those epitopes. We have also shown that this response was size dependent. This project aims to further explore the effect of size and morphology on the efficacy of nanoparticle vaccines. Aims: 1) Produce and self-assemble multi-epitope vaccine constructs. 2) Fully characterize nanoparticles, including arrangement of the epitopes on the surface.



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PROFESSOR MATT TRAU Australian Institute for Bioengineering and Nanotechnology (AIBN) Phone: 07 3346 4173 Email: [email protected]

Our Centre for Biomarker Research and Development is located in the Australian Institute for Bioengineering and Nanotechnology (AIBN) and has access to state-of-the-art chemistry synthesis, and characterisation facilities. Students working in the Centre will have the opportunity to create nanoscaled biosensors for applications in cancer, infectious disease, therapeutics and point-of-care devices. Students will also be given the opportunity to work with leading geneticists, epigeneticists and clinical researchers to test these devices in clinical settings. The Centre has a focus on developing diagnostic devices for early detection of diseases such as cancer, when it is most responsive to treatment which also provides the greatest social and economic benefits to society. Nanotechnology offers the promise of miniaturized, inexpensive, flexible and robust “plug-and-play” molecular reading systems which can be effectively deployed to detect diseases in a clinical setting. Current projects available include: 1) Microfluidic Devices for Capturing Rare Circulating Tumour Cells The progression of cancer in patients is characterized by cells that invade locally and travel through the blood stream to metastasize in the other parts of the body. These cells, account for 1 or fewer cells in 106 blood cells and are known as circulating tumour cells (CTCs). Development of advanced technologies for capturing CTCs in blood in the early stage of the metastasis process would transform the treatment of cancer. This project strives to build and test a microfluidic device to enable selective capture and detection of CTCs using threedimensional microstructured electrodes within the the device. 2) Nanodevices/Nanobiosensors for Cancer Biomarker Proteins Detecting low concentrations biomarkers in serum is potentially useful for the diagnosis and prognosis of a disease. The development of a detection method that is rapid and cheap could revolutionize the treatment of diseases such as cancer. In this project, we aim to fabricate nanobiosensors with nanostructured 3D-electrodes to detect single protein molecules in blood. Students will achieve hands on experience in the design, fabrication and application of the microfluidic devices and electrochemical micro(nano)biosensors. 3) DNA Nanomachinery for Early Breast Cancer Detection Subsets of non-coding (nc) RNAs serve as potential biomarkers of diseases. This project involves designing, developing and evaluating novel DNA nanomachinery to perform tasks that are currently beyond the reach of existing molecular readout technologies. We aim to use these nanomachines as a new technology platform to rapidly detect ncRNA biomarkers in breast cancer patients. This interdisciplinary project will provide an opportunity for students to acquire diverse skills in chemistry, molecular biology and bioengineering. 4) Point-of-Care Diagnostics Point-of-care (POC) diagnostics have the potential to revolutionise global health care by enabling diseases to be rapidly diagnosed ‘on the spot’ using minimal specialised infrastructure. POC devices need to be highly sensitive, specific, practical, cost effective and portable if they are to be used in resource limited settings. We are focused on novel and simple (nanotechnology-based) molecular assays to generate new POC diagnostic technologies. Students will be involved in designing, developing and evaluating methods to rapidly detect pathogenic DNA using devices such as mobile telephones. This interdisciplinary project will provide an opportunity to acquire diverse skills in chemistry, molecular biology, bioengineering, and biotechnology.



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THE ADVANCED WATER MANAGEMENT CENTRE (AWMC) Honours Projects at The Advanced Water Management Centre (AWMC) Students with interests in environmental microbiology/biotechnology, wastewater treatment processes, environmental chemistry, microbial ecology and function, and/or application of molecular approaches, are encouraged to apply for Honours projects listed here. The AWMC is an international centre of excellence for innovative wastewater technology and management, with over 15 Research Academics and more than 50 graduate students (see http://www.awmc.uq.edu.au/). If you are motivated by our exciting science and interested in honours projects or higher degrees then please get in contact with either Dr Phil Bond, [email protected]; or directly contact the academics listed with the project descriptions below. For Honours students that qualify at the AWMC a tax free stipend of $3000 can be available (subject to the project). Research Interests and Graduate Research Projects Our research focuses on wastewater treatments systems, polluted environments, production of energy from waste, ocean biogeochemistry, water recycling and solid waste treatment. Below are examples of research topics available as Honours projects at the AWMC; further projects are available within the centre, please enquire. 1. Determining the mechanism of free nitrous acid inhibition on biofilm activity of wastewater microorganisms. / Dr Chris Lu Fan, Dr Phil Bond and Prof Zhiguo Yuan There is great interest in disruption or destruction of problem microbial biofilms. This project will investigate the disruptive effect of a toxin, nitrous acid, on microorganisms relevant to wastewater treatment biofilms, with the aim to determine molecular and physiological understanding of the toxic effect.

2. Turning emissions into fuels using electricity-boosted fermentation. / Dr Jens Kroemer Microbial electrosynthesis is a cutting edge technology to produce valuable products from oxidised carbon sources. This study will apply bioelectrochemical systems to boost the bio-production of fermentation products by Clostridia. 3. 1,3 propanediol production from glycerol using microbial electrosynthesis with Citrobacter ssp. / Dr Jens Kroemer Microbial electrosynthesis is a cutting edge technology to produce valuable products from oxidised carbon sources. This study will explore the production of 1,3 propanediol from glycerol in a engineering Citrobacter species. The project is a collaboration between the Centre fro Microbial Electrosynthesis at UQ and the University of Ghent in Belgium. 4. Determining the microbes that are eating our sewer pipes. / Dr Guangming Jiang, Dr Phil Bond and Prof Jurg Keller Certain microorganisms cause massive problems in sewers by forming biofilms on the concrete and producing sulfuric acid that corrodes the concrete pipes. This project will investigate the molecular ecology and microbial activities to understand the effects of treatments aimed to mitigate this problem. 5. Influence of soluble organics on struvite crystallization. / Dr Chirag Mehta and Dr. Damien Batstone Struvite crystallization technology is being widely applied in full-scale to remove phosphorus from wastewater. This project will investigate influence of soluble organics on struvite crystal formation through solubility, growth rate, product size distribution, and product quality measurements. 6. Binders for struvite granulation. / Dr Chirag Mehta and Dr. Damien Batstone There is great interest to formulate and test waste derived fertilizer product (struvite). This study will investigate role of different binders on mechanical and agronomic properties of the granulated product


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COOK AUSTRALIA PTY LTD

Address: 12 Electronics Street, Eight Mile Plains QLD 4113 Phone: 07 3365 4612 Email: [email protected] A range of possible projects is available. Applicants for this project should contact Prof Ross Barnard in the first instance. Cooks contribution: Cook will provide project supervision and ongoing advice.



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QUEENSLAND ALLIANCE FOR AGRICULTURE & FOOD INNOVATION (Centre for Animal Science)

DAFF Biotechnology Laboratory, Level 3, Building 80, UQ-St Lucia Campus Phone: 07 3255 4535 or 07 3255 4529 or 07 3255 4527 Website: http://www.qaafi.uq.edu.au/cas

(Left) Dr Manuel Rodriguez Valle: Molecular Parasitologist and Molecular Immunologist (Middle) Dr Ala Lew-Tabor: Molecular Biologist (Right) Dr Jess Morgan: Molecular Parasitologist

Applied Animal Disease Biotechnology Research Opportunities:There are options for Honours, Masters or PhD research with the group. It is an opportunity to obtain industry or animal health research experience. Project 1: Cattle tick vaccine research – Drs Ala Lew-Tabor and Manuel Rodriguez Valle-Rhipicephalus (Boophilus) microplus, or the cattle tick, has a high impact on the cattle industry, costing Australia $175m per annum. The aim of the research is to identify tick vaccine candidates and produce novel vaccine candidate antigens using yeast expression systems. Research programs can be developed to include gene cloning, yeast expression, development of novel hybrid molecules (to enhance immune protection), and protein purification and analysis. Research also includes the study of tick protein biological function during host:parasite interactions. Project 2: Paralysis tick vaccine research – Dr Manuel Rodriguez Valle - Ixodes holocyclus (paralysis tick) causes fatal paralysis in companion animals and livestock, with approximately 100,000 toxicoses cases reported along the east coast of Australia annually. Research to develop a protective vaccine has recently commenced with good opportunities for research students. Research can include: bioinformatics to study next gen transcriptomic data, expression analysis, vaccine antigen construction (including hybrid molecule construction to enhance immune protection), yeast display library screening, immune screening, toxicity screening using tissue and laboratory animals, and the study of tick protein biological function during host:parasite interactions. Project 3: Eimeria diagnostics - Dr Jess Morgan - Coccidiosis of chickens is an economically important disease caused by infection with species of Eimeria. Seven recognised species occur in Australia but they

are difficult to distinguish morphologically. DNA-based diagnostic technology has been developed to distinguish the seven species. Current research is investigating if genetic markers can be used to distinguish different populations within species. DNA-based technologies in use include traditional and next generation DNA sequencing, real-time PCR, SNP analysis and microsatellite screening. Project 4: Bovine genital campylobacteriosis - Dr Ala Lew-Tabor. - BGC is reproductive disease of cattle which is difficult to diagnose. Research includes subspecies the development of novel assays (real time PCR and high resolution melt methods) to distinguish the causative pathogen Campylobacter fetus subsp venerealis from closely related Campylobacter spp. Project 5: Tick fever diagnostics and vaccine development - Drs Ala Lew-Tabor, Jess Morgan and Manuel Rodriguez Valle - Tick fever is caused by protozoan parasites Babesia bovis and B. bigemina and the rickettsia Anaplasma marginale. These pathogens are transmitted by the cattle tick (Rhipicephalus microplus) and can cause fatal disease in cattle in northern Australia. These diseases are currently managed through the implementation of a live vaccine program (Department of Agriculture, Fisheries & Forestry). Together with DAFF, CAS scientists are developing improved methods to differentiate vaccine and field isolates (real time PCR and high resolution melt methods), as well as novel safe vaccine delivery systems.

http://www.qaafi.uq.edu.au/cas


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DR NEENA MITTER

QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI) Queensland Agricultural Biotechnology Centre (QABC), St. Lucia Campus Phone: 07 3346 6513 Email: [email protected] Website: http://www.qaafi.uq.edu.au/

Project 1: RNA silencing based resistance to fungal diseases RNA silencing has proven to be an emerging strategy to control plant viruses and nematodes in agricultural crops. Transgene- mediated virus resistance is a classical example of RNA silencing and its role in antiviral defence in plants. There have been many examples of transgene mediated resistance using viral sense, antisense or inverted repeat sequences for targeting RNA viruses, DNA viruses and viroids. In fungi, RNA silencing phenomenon was called Quelling when first described in Neurospora crassa in 1992. This technology of transgene induced RNA silencing can be exploited to control fungal diseases of economic importance. The project will involve elucidation of the mechanism of RNA silencing based host delivered resistance against fungi. Project 2: Artificial MicroRNA-Mediated Virus Resistance in Plants RNA silencing in plants is a natural defense system against foreign genetic elements including viruses. This natural antiviral mechanism has been adopted to develop virus-resistant plants through expression of virus derived double-stranded RNAs or hairpin RNAs, which in turn are processed into small interfering RNAs (siRNAs) by the host’s RNA silencing machinery. While these virus-specific siRNAs were shown to be a hallmark of the acquired virus resistance, the functionality of another set of the RNA silencing-related small RNAs, microRNAs (miRNAs), in engineering plant virus resistance has not been extensively explored. The biogenesis of mature miRNAs is not affected if few nucleotides are changed in the mature miRNA sequence. By replacing natural mature miRNA sequences in the precursors with the virus specific sequences, resistance may be obtained against plant viruses. The project will involve making amiRNA constructs targeting plant viruses and using transient and stable expression in model plants for enhanced resistance. Project 3: Plant based expression of viral proteins for nanoparticle based vaccine delivery Plants (both whole plants and in vitro cultures) are gaining attention for the large-scale production of recombinant proteins and particularly, as a promising platform for vaccine production. Some of the advantages of the plant-based systems are that they can rapidly be bulked to large biomass, its maintenance is relatively inexpensive, and they do not harbor mammalian proteins or pathogens. Protein production could be achieved through stable or transient expression. The current project will investigate plant based expression system for some of the antigens targeting veterinary diseases. Project 4: Micro RNA expression in Avocado in relation to root initiation Clonal propagation of commercially used cultivars is required to meet the demand of the growers for clean and genetically uniform disease free material. Clonal propagation enables multiplication of elite rootstocks and other identified cultivars that have desirable traits such as disease resistance and increased yield/fruit quality, which benefits industry. Root initiation in cuttings of desired cultivars can be a major hurdle in clonal propagation especially with reference to tree crops. MicroRNAs (miRNAs) have been found to regulate the expression of genes essential for the various biological mechanisms in plants as well as animals. The project will involve characterization of miRNA expression in horticultural crops like avocado to understand the mechanism of root initiation.


http://www.qaafi.uq.edu.au/


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JESSICA FERGUSON ADAM CHAPMAN

SIRROMET WINERY, 850 Mt Cotton Rd, Mt Cotton Qld 4165 Phone: 07 3206 2999 Email: [email protected]

With every vintage, new challenges emerge in winemaking. Over the past 5 years Queensland vintage weather conditions have varied enormously requiring constant vigilance and innovation by the winemaker to maintain consistency of quality and wine style. Several emerging patterns have prompted the need for investigation into specific wine processing issues. The following suggestions for projects are intended to address current dilemmas in winemaking in Queensland, and have the potential to provide real solutions to the industry. NOTE: Projects may be carried out in part, or completely, at Sirromet Wines Pty Ltd on Mt Cotton Road, Mt Cotton. Students will need to arrange their own transport. EXAMPLES OF POSSIBLE PROJECTS ARE: ‘Pinking’ – non desirable colour shifts in Pinot Gris and Verdelho varieties. Investigation of different wine matrices (pH, SO2 levels, phenolics content, degree of chemical reductive environment) on Pinot Gris colour. Investigation of pinking precursors in must and wine, investigation into must handling techniques on precursor levels in juice and wine. Assessment of various fining methods in removing pinking precursors. Quercetin dihydrate in red varieties, levels, weather influences (drought years versus normal). Critical levels of quercetin dihydrate for likely precipitation from wine. Fermentation influences on quercetin concentrations and stability. Wine matrix variables affecting stability/precipitation of quercetin dihidrate over time. Total phenolics levels in red wines, a measure of quality? Assessment of simple empirical determinations of phenolic groups vs accurate instrumental assays (HPLC). Correlation with expert tasting assessments. Are there relationships/interactions between DO2, FSO2 and DCO2 in finished wines? Yeast population desired levels in sparkling secondary fermentations given various alcohol, protein, TSO2, VA and phenolics levels. Investigation of different sparkling yeast tolerance to high TSO2 levels with influences from pH, alcohol and VA. Resveratrol levels in Granite Belt red wines – varietal differences, significance of altitude/soil, vintage/climate conditions, fruit condition, ripeness & canopy cover during ripening. Resveratrol levels in grapes versus wine. Stability of resveratrol in wine over time. Extracting red grape skins for resveratrol with a view to developing a suitable colourless extract to enrich red wines with resveratrol without affecting wine taste, colour or mouthfeel. N, P, K, Fe levels in juices pre-fermentation for direct sugar accumulation via yeast. Copper additions prior to bottling – investigation into effects on protein stability and potential to cause copper casse formation. Browning in white wines as a result of interaction between copper and excess phenolics in white wine.



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DR LINDA LUA

Protein Expression Facility Australian Institute for Bioengineering and Nanotechnology Phone: 07 3346 3979 Email: [email protected] Website: www.uq.edu.au/pef

Project 1: Mass manufacturing viral vaccines for pandemic influenza The ideal way to protect against pandemic flu is to vaccinate the entire Australian population as soon as possible after a dangerous strain starts to spread. Current manufacturing technology, which begins by making an infectious virus in chicken eggs, is unable to quickly deliver a mass vaccine to the entire Australian population. Recent

scientific progress has demonstrated that it is possible to make a non-infectious “empty” virus shell (virus-like particle) inside cells. This new product is able to provide full protection against a lethal influenza challenge, when administered nasally. Our approach relies on the expression and purification of key influenza virus proteins, which are then processed in reactors into non-infectious virus-like particles. Skills: Cloning, site-directed mutagenesis, bacterial protein expression, protein purification, biophysical analysis of protein. Project 2: High throughput parallelised protein production Obtaining large quantities of pure proteins for structural and functional analysis remains a main bottleneck in biological research and pharmaceutical development. As no universally applicable expression system exists, it is often necessary to test several expression systems to achieve a desired outcome. A HTP platform for parallelised cloning and expression in E.coli is established in our lab. Further development in HTP expression using other eukaryotic systems (yeast, insect cell and mammalian cell) is on-going in our lab. Skills: Cloning, protein expression in different hosts (E.coli, yeast, insect cells and mammalian cells), protein purification, protein analysis. Project 3: Novel protein purification technologies Recovery of the protein of interest from a culture is just as important as obtaining the expression the protein. The end application of the purified protein determines the level of purity and yield required. Minimising protein lost and maximising protein purity in a simple purification process is desirable. We are developing new purification technologies (chromatographic and non-chromatographic) to improve the purification of different types of proteins and from different expression host systems. Skills: Protein expression in different hosts (E.coli, yeast, insect cells and mammalian cells), protein purification, protein analysis.


http://www.uq.edu.au/pef


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ASSOCIATE PROFESSOR CRAIG WILLIAMS

Natural product total synthesis, isolation and associated medicinal chemistry. Drug Design and Development / Green chemistry Phone: 07 3365 3530 Email: [email protected]

Anti-cancer, neurodegenerative disease and insect active limonoids: [in collaboration with Dr Paul Savage (CSIRO), Prof. Peter Dodd (SCMB. UQ) and A/Prof. Gimme Walter (SBS, UQ)]. Recently we achieved the total syntheses of a number of the limonoid family members, such as, Khayasin 1 and Cipadonoid B 2. The synthesised limonoids 1 and 2 are closely related to Gedunin 3, another limonoid family member, which displays anti-cancer and neurodegenerative disease activity in Heat Shock protein 90 (Hsp90) models. We would now like to investigate the total synthesis of gedunin 3, which has yet to be reported, and explore the gedunin 3 structure against Hsp90 using state of the art medicinal chemistry techniques. Cubane Chemistry: A Benzene Ring Drug Isostere? [in collaboration with Dr Paul Savage (CSIRO) and Prof. James De Voss (SCMB, UQ)]. Cubane 4, when viewed from the corners (i.e. 5) can be considered roughly the same size as a benzene ring (i.e. 6). This is equally true when you take into consideration the clouds of benzene, that is, cubane 4 is about the same “thickness”. Therefore the 1,2- 1,3- and 1,4- substituted cubanes are similar to ortho-, meta-, and para-substituted benzenes respectively. Furthermore, the cubane structure is actually very stable – cubane ring-opening is thermally disallowed by orbital symmetry. With this in mind the project would involve replacing the phenyl ring in a current drug molecule and comparing bioloical assay data. It would also be expected that cubane 4 has completely different P450 metabolism profiles, which will be explored in collaboration with Prof. James De Voss. Discovery and Development of Novel Analgesics [in collaboration with Prof. Maree Smith from the Centre for Integrated Preclinical Drug Development (CIPDD)/TetraQ)]: The prevalence of painful diabetic neuropathy (PDN) is 7% within a year of diagnosis of diabetes and 50% by 25 yrs of diabetes. The medicines currently used to treat PDN are not effective in less than 50% of patients. Hence, we propose to develop new, effective medicines for the alleviation of PDN by investigating the biology (Smith lab) of unusual heterocycles (Williams lab) that deliver the neurotransmitter molecule NO (nitric oxide). Green Chemistry [in collaboration with Prof. Ian Gentle (SCMB, UQ)]. Organic reactions are key to new molecules that are in ever-increasing demand for applications in the pharmaceutical, materials and agrichemical sectors. This demand, however, places growing pressure on synthetic chemists to limit or even eradicate environmentally unfriendly chemical waste production. Steps towards such measures are now commonly termed “Green Chemistry”. Projects looking at developing new solvents and new surfactants are available. Applying physical techniques [e.g. small angle scattering (SAXS), neutron scattering (SANS) and dynamic light scattering (DLS)] to understand macromolecular mechanisms is an important part of the work. A/Prof. Williams (ARC Future Fellow) he has held past and present multimillion dollar industry research contracts in addition to ARC and NHMRC grants. Further projects are available on request.


SCMB Biotechnology Research Projects 2016 | Group Profiles

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CENTRE FOR NUTRITION & FOOD SCIENCES (CNAFS) QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI)

DR EUGENI ROURA (Left)

Phone: 07 3365 2526 Email: [email protected]

DR NADIA DE JAGER (Right)


MOLECULAR NUTRITION, METABOLISM AND TASTE The world of taste perception and our understanding thereof is in the process of undergoing significant expansion. Taste receptors have been uncovered as a network of nutrient sensors present not only in the oral cavity, but also in many other parts of the body, including heart, gastrointestinal tract and brain. The roles that these receptors play outside the mouth is not completely understood, however current findings suggest that they are involved in the fundamental process of controlling the hunger-satiety cycle and food intake. Our research group aims to gain a better understanding of how the taste system responds to different nutritional paradigms. Model systems for studying common eating disorders such as obesity and anorexia are assisting us in addressing our research questions. Project 1: How are nutrients sensed in the gastrointestinal tract? The role of taste receptors. In order to bridge gaps in the current understanding of how nutrients are sensed in the gastrointestinal tract, a number of molecular and cell biology techniques will be employed. For example immunohistochemistry, gene expression and in situ hybridisation techniques will allow for the identification and quantification of key candidate gene expression and protein levels. A background in biomedical sciences or animal physiology is recommended for this project. Project 2: Knowing more about your sense of taste – applications to obesity research Humans have 25 different types of bitter taste receptors that can detect and taste many more bitter compounds. Our ability to sense these compounds are believed to be associated with an evolutionary advantage for sensing and therefore avoiding potential toxic or harmful substances. Individual variation exists at the molecular level where the genes encoding the bitter taste receptors can have mutations. Different vegetables contain different kinds and different amounts of bitter compounds. Bitter compounds have been shown to have a remarkable ability to elicit a “fuller for longer” feeling and is therefore relevant to obesity research. This project will investigate mutations in bitter taste receptor genes and links with bitter compounds commonly found in vegetables. Project 3: Biotechnology and Food Science Fibre is known to have wide reaching health benefits and is being consumed in increasing amounts as part of a human diet. However, there appears to be more to the story, at least in rodents, where it was shown that excessive consumption of dietary fibre was associated with increased susceptibility to bacterial infections. Pigs are ideal model animals for humans and this project will investigate changes occurring in pig tissues (already collected) as a consequence of fibre. To address this objective, modern biotechnology techniques will be used by measuring the relative gene expression levels by real time PCR of candidate genes associated with hunger and satiety as well as genes that serve as markers for inflammation.




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DIAMANTINA INSTITUTE FOR CANCER, IMMUNOLOGY & METABOLIC MEDICINE

PROFESSOR RANJENY THOMAS

Arthritis Qld Chair of Rheumatology Immunology Programme Address: Princess Alexandra Hospital, Buranda Phone: 07 3240 5365 Email: [email protected]

Project 1: Pathogenesis of inflammatory arthritis in skg mice Self-reactive T cells with a low signalling capacity through the T cell receptor have been observed in the SKG mouse model of rheumatoid arthritism, and have been linked to a spontaneous mutation in the ZAP-70 signal transduction molecule. This project examines the role that antigen presenting dendritic cells play in the development of arthritis in this model, and whether dendritic cell immunotherapy can be used to treat arthritic mice. Suitable for: PhD, Masters or Honours. Project 2: Human type 1 diabetes We have developed a new diagnostic assay which identifies individuals with Type 1 diabetes (T1DM) and some of their relatives at risk of diabetes. Exposure of blood monocytes to the bacterial product lipopolysaccharide led to an abnormally low level of activation of the protein, RelB. We are now extending these studies to determine the value of the assay for predicting whether otherwise healthy siblings of children with T1DM will develop diabetes in the future. This would allow us to identify those at risk so that they could be treated earlier or encouraged to make preventative changes to their lifestyle. This project involves analysis of factors contributing to the abnormal RelB test, and researching ways in which RelB function can be restored in these dendritic cells, for new treatments. Suitable for: PhD, Masters or Honours.

DR RAYMOND J. STEPTOE


Project: Gene Therapy for Autoimmune Disease Autoimmune diseases develop when the body’s immune system mistakenly attacks normal, healthy body tissues. We are interested in developing approaches to prevent or treat autoimmune disease. Dendritic cells are important educators of the immune system and control both immunity and tolerance to self-tissues. We have demonstrated that steady-state antigen-expressing dendritic cells can turn off responses in not only naïve T cells, but surprisingly, also in memory T cells. We are now seeking ways to apply this knowledge to develop a vaccine-like approach to therapy of autoimmune diseases. Projects are available that examine the basic immune biology of immune tolerance or novel methods of in vivo gene transfer that can achieve immune tolerance.




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DR KRISTEN RADFORD

Immunotherapy Program Mater Medical Research Institute Phone: 07 3163 2567 Email: [email protected]

Targeting the Human Cross-priming Dendritic Cells for Immunotherapy Background: Dendritic cells (DCs) are the key antigen presenting cells responsible for initiating and directing immune responses. In mice there are distinct dendritic cell subsets that are specialised in the types of immune responses they generate. However, dendritic cells are poorly understood in humans and translation is complicated by differences in human and mouse immune systems and in particular expression of pattern recognition receptors. We have identified a rare human DC subtype, termed CD141+ DC, that we hypothesize plays an important role in the induction of immune responses against viruses and cancers by their specialised ability to stimulate cytotoxic T cells. These DC are attractive targets for the design of new vaccines against cancers and infectious diseases. This project will explore the interaction of CD141+ DC with tumour cells and virus-infected cells and the mechanisms by which they generate cytotoxic T cell responses. Hypotheses: CD141+ DC are specialized in the induction of cytotoxic T cell responses and as such are attractive vaccine targets Specific Aims: Project 1: To study the function of CD141+ DC and their response to pattern recognition receptors in human tissues and in a humanized mouse model. Project 2: To investigate the interactions of different human DC subsets with tumour cells. Achievable outcomes: • Training in human cellular immunology, cancer immunology and immunotherapy. • Expertise in isolation of primary human cells, primary cell culture, flow cytometry analysis and sorting, other immunological assays (eg cytokine ELISAs), PCR • Expertise in a novel humanised mouse model



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MATER MEDICAL RESEARCH INSTITUTE

The Role of Inflammation and Immunity in Gynaecological Cancer Therapy Laboratory: Cancer Therapeutics Supervisor/s: David Munster, Jim Coward, Kristen Radford Funding: Team budgets

Student Objectives • To develop an understanding of the investigation of human cancer therapy • To develop the ability to identify key scientific questions, to design optimal experiments to address the questions, to efficiently carry out the experiments, to interpret the results and report the outcomes • To learn a variety of research techniques (see below) • To develop the ability to interact with team members and collaborators to maximise outcomes Project Overview: Ovarian cancer patient survival is the poorest of all gynaecological cancers, due to late diagnosis and to poorly effective therapies. Evidence is increasing that improvements in therapeutic outcomes will require control of inflammatory mediators and appropriate stimulation of the patient’s immune system. We have access to relatively large quantities of primary tumour material from patients with ovarian cancer and other gynaecological malignancies. This is an important resource for research and the development of better therapies. Available Projects: • Determination of inflammatory cytokines in samples from patients with gynaecological cancer • Phenotype and functional characterization of leukocytes in samples from patients with gynaecological cancer • How does the gynaecological cancer microenvironment impair anti-cancer therapy? • Testing therapies on primary human gynaecological cancers in vitro and in mice Achievable Outcome: Generation of novel data that may lead to improved treatment of cancer Techniques : This project will introduce the student to a range of techniques: Cell and molecular biology methods, cellular immunology, human tissue handling, small animal experimentation, ELISA, and flow cytometry. Relevant Publications 1. Pearson, T. et al., Humanized SCID mouse models for biomedical research. Curr Top Microbiol Immunol. 2008;324:25-51. 2. Coward, J. et al., Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res. 2011;17(18):6083-96. Further Information Dr David Munster Phone: 07 3163 2571 Email: [email protected]


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POLYMER CHEMISTRY GROUP

PROFESSOR ANDREW WHITTAKER

GROUP LEADER, Australian Institute for Bioengineering & Nanotechnology (AIBN) Phone: 07 3346 3885 Email: [email protected] Website: www.uq.edu.au/polymer-chemistry/ Our research group develops polymeric materials to improve human health. Our large group of researchers have programs of research across the spectrum from bench top-

to-bedside. Specifically we work in the fields of sensing of disease, delivery of drugs and regeneration of tissue. The projects listed below are all done in collaboration with experts in clinical application of biomaterials, and will provide a solid foundation in practical and theoretical aspects of the use of polymeric materials as biomaterials. Honours projects are available in the following areas (for project details, please see our website or contact Andrew by email). The web site lists other projects. 1. Functionalisation of the surfaces of titanium alloys for improved osseointegration 2. Development of novel polymer scaffolds to aid the repair of the spinal cord 3. Development of low-fouling, anti-microbial surface coatings 4. Novel polymer molecular imaging agents (MRI) for early disease detection 5. Peptide hydrogels for cell delivery


http://www.uq.edu.au/polymer-chemistry/


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PROFESSOR MATT TRAU DR ASHLEY CONNOLLY

Centre for Biomaker Research and Development, Australian Institute for Bioengineering & Nanotechnology (AIBN) School of Chemistry & Molecular Bioscience (SCMB) Phone: 07 3346 4173(Matt) / 07 3346 4172(Ashley) Email: [email protected] / [email protected]

1) DNA Nanomachinery for Early Breast Cancer Detection Every 3 minutes a woman is diagnosed with breast cancer. Despite the increasing incidence of breast cancer in the Western world, death rates have been decreasing since 1990. This is the result of treatment advances, increased awareness and early detection. It is widely accepted that early detection results in much higher survival rates, but it is proving difficult to detect the cancer in its early stages. Subsets of RNA that are not translated into proteins have recently been identified in cancerous growths. These non-coding (nc) RNAs serve as potential biomarkers of disease. Our group is designing, developing and evaluating novel DNA nanomachinery to perform tasks that are currently beyond the reach of existing molecular readout technologies. We aim to use these nanomachines as a new technology platform to rapidly detect ncRNA biomarkers in breast cancer patients. This interdisciplinary project combines the latest developments in molecular genetics with cutting edge nanobiotechnology and will provide an opportunity for students to acquire diverse skills in chemistry, molecular biology and bioengineering. 2) Point-of-Care Diagnostics Point-of-care (POC) diagnostics have the potential to revolutionise global health care by enabling diseases to be rapidly diagnosed ‘on the spot’ using assays that require minimal specialised infrastructure. The simplicity of POC assays enables them to be performed by health care workers or even the patient, which enables rapid diagnosis of a disease. This improves the time taken to treat a disease, leading to better patient care and a reduced rate of mortality and morbidity. POC devices need to be practical, cost effective and portable with high sensitivity and specificity if they are to be used in resource limited settings.

Within our Centre we have an ongoing research program focused on designing and building simple (nanotechnology-based) molecular assays to generate new POC diagnostic technologies. This Honours project will be involved in designing, developing and evaluating novel methods to rapidly amplify and ultimately detect pathogenic DNA and RNA using everyday devices such as mobile telephones. This interdisciplinary project combines the latest developments in biological chemistry with cutting edge nanobiotechnology and will provide an opportunity to acquire diverse skills in chemistry, molecular biology, bioengineering, and biotechnology.




22

PROFESSOR MATT TRAU DR MUHAMMAD SHIDDIKY

Centre for Biomarker Research and Development, Australian Institute for Bioengineering & Nanotechnology (AIBN) School of Chemistry & Molecular Bioscience (SCMB) Phone: 07 3346 4173 (Matt) or 07 3346 4169 (Muhammad) Email: [email protected] / [email protected]

1) Microfluidic Devices for Capturing Rare Circulating Tumour Cells As cancer mortality rates continue to rise, the national impact of the cancers is beginning to overwhelm healthcare services. The progression of cancer in patients is characterized by cells that invade locally and metastasize to nearby tissues or travel through the blood stream to set up colonies in the other parts of the body. These cells, accounting for 1 or fewer cells in 105 – 106 peripheral blood mononuclear cells, are known as circulating tumour cells (CTCs). Development of advanced technology for capturing CTCs in blood in the early stage of the metastasis process would be transformative in the treatment of cancer. This project strives to build and test a microfluidic device with the capacity to enable selective capture and sensitive detection of CTCs by incorporating three-dimensional microstructured electrodes within the detection/capture domain of the device. 2) Nanodevices/Nanobiosensors for Cancer Biomarker Proteins The clinical use of immunoassays in treatment of cancer at early stages of the disease requires detection of proteins of typically 10-16 to 10-12 M concentration in whole blood, blood plasma or serum samples. Detecting this low concentration of proteins is potentially useful for identifying individuals at risk and for clinicians to prescribe preventive measures for these individuals. Current immunoassay technologies typically measure the proteins at concentration above 10-12 M. The development of a detection method that is rapid, cheap, and more sensitive than those currently available could revolutionize many medical treatments in areas such as cancer. In this project, we aim to fabricate nanobiosensors with nanostructured 3D-electrodes to detect single protein molecules in blood. Via these projects, students will achieve hands on experience in the design, fabrication and application of the microfluidic devices and electrochemical micro(nano)biosensors.

SCMB Biotechnology Research Projects 2016 | Individual Contributors

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ASSOCIATE PROFESSOR SASSAN ASGARI

School of Biological Sciences Phone: 07 3365 2043 Email: [email protected]

Insect host-pathogen molecular interactions In my laboratory, we are investigating the evolutionary adaptations that are employed by parasites and pathogens of insects to avoid host immune defence reactions. This will further our understanding of the interactions but also lead us to the discovery of biogenic molecules with agrochemical and pharmaceutical properties with potential applications in biotechnology. Examples of available projects are: Project 1: Role of microRNAs in host-pathogen interactions MicroRNAs are small non-coding RNAs that play important roles in gene regulation in metazoans, plants and viruses. Their roles in development, cancer, apoptosis, immunity, longevity, and viral infections have been established. We are investigating the role of these small molecules expressed from insect viruses or insect host cells in host-pathogen interactions and virus biology. We are using a variety of host-pathogen systems, including Dengue virus-, West Nile virus-, Wolbachia-mosquito interactions. This project is in the most rapidly developing area of microRNA research and provides a basis for designing smart strategies to control insects of medical or agricultural significance.


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ASSOCIATE PROFESSOR ANDREW C. BARNES

School of Biological Sciences & Centre for Marine Science Phone: 07 3346 9416 Email: [email protected]

Host-microbial interactions in aquatic animals Marine and aquatic animals exist directly immersed in an environment that supports abundant and diverse microbiota. This provides both unique opportunities and challenges for aquatic animals that are not experienced by their terrestrial counterparts. My research explores the interactions of marine fish and invertebrates with predominantly bacterial associates, both beneficial and pathogenic, focusing on aquatic animal health. Much of my research is applied, having strong collaborations with the aquaculture and veterinary industry both in Australia and overseas. Comparative immunology At the molecular and cellular level, the first point of contact between aquatic animals and environmental microbes is their immune system. We have explored the immune systems of invertebrates such as corals, prawns and oysters, as well as commercially and ecologically important marine fish at both the molecular and functional level. We have identified roles in pathogen exclusion and symbiont selection. At the applied level we have exploited this to develop commercial vaccines for barramundi, improve vaccine adjuvants for fish and to develop tools for marker-assisted selection of disease resistant oysters. At the fundamental level we have identified the first functional immune proteins in reef-building corals and determined their roles in microbial community control and selection of the symbiotic dinoflagellate. Bacterial pathogenesis Ultimately, most bacterial invaders are eliminated by macrophages. Therefore, understanding how pathogens circumvent these phagocytic cells is critical in development of vaccine targets. We investigate interactions of pathogenic bacteria with primary leucocyte cultures derived from commercially and ecologically important marine fish species with a view to developing improved vaccines, or explaining why particular epizootics have arisen. Current work focuses on evolution of the capsular operon of S. iniae in response to on-farm vaccination, and on tracing origin and explaining pathogenesis of group B Streptococcus in wild Queensland grouper using genomics and functional assays. Microbial communities Aquatic animals have complex microbial communities that strongly influence health and growth. The complexity of the communities is confounded further by extremely high variability amongst individuals. We investigate microbial communities with sufficient replication to provide data that can be used predictively or to solve particular issues. In highly replicated studies we have shown strong host –specific selection of bacterial associates in reef-building corals. We have also shown what happens to the metabolically active gut microbiota of Atlantic salmon during the stress of warm summer water temperatures in Tasmania, enabling formulation of novel more sustainable feeds to improve stability of the gut microbiome and improve fish performance during the summer months. Project 1: Serotype switching in marine streptococcus from barramundi and grouper Project 2: Markers for immune cells in barramundi


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PROFESSOR CHRISTINE BEVERIDGE

Centre for Integrative Legume Research School of Biological Sciences Phone: 07 3365 7525 Email: [email protected]

A new plant hormone In a recent publication in the journal Nature we identified strigolactone as a new plant hormone. We now understand that this hormone is involved in a range of processes in plants that are important for plant productivity. We have several new mutants that affect shoot branching and which may act on this pathway. Several neat projects are available elucidating the genetic and physiological function of the genes involved and the pathways they control. Novel plant signals Plants respond to decapitation very rapidly via unknown processes. We have discovered several genes which show changes in expression and may underpin this important developmental process. In this project you will investigate these genes and other tools to determine how plants can respond so quickly to this potentially devastating treatment. Integration of plant development We are interested in how the body plan of the shoot is controlled and how branching and flowering control systems are integrated into developmental strategies adapted to the environment. We use genetic, physiological and computational modelling (see our recent Plant Cell paper) to create and evaluate models of the biological networks involved. In this research area, you will be allocated a tight project adapted to your particular skills and needs.


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ASSOCIATE PROFESSOR JOANNE BLANCHFIELD School of Chemistry & Molecular Biosciences Phone: 07 3365 3622 Email: [email protected]

Synthesis of revolutionary synthetic vaccine constructs (project with Prof. Paul Burn) We have a collaboration with Prof. Paul Burn that concerns the construction of fully synthetic vaccine structures against HIV and Staphlycoccus aureus. For details of the project please contact Joanne Blanchfield or Paul Burn. This project would involve: • organic synthesis • carbohydrate synthesis • solid phase peptide synthesis • cell culture and plasma stability assays and aseptic techniques • assay development and molecule characterisation including use of HPLC, LC/MS, NMR, GC/MS equipment. Bioavailability of natural products from herbal extracts. (Project with Prof. James De Voss) Herbal remedies are a major source of medical treatment for much of the world’s population. Unfortunately, little is known about the fate of the natural products in the extracts or which, if any are biologically active. We are offering a project that uses a cellular model of the small intestine (Caco-2 cell monolayers) to investigate which natural products are likely to enter the blood stream after oral intake of some popular herbal remedies. We also look closely at what changes the compounds undergo during digestion and absorption. • use of preparative and analytical HPLC equipment to isolate and identify potentially active compounds from herbal extracts. • performance of in vitro biological assays to determine permeability (Caco-2 cell assay), stability (CC2 homogenate assay, plasma stability) assays. • Analytical analysis using LC/MS and HPLC of the solutions resulting from the in vitro assays.


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PROFESSOR JIMMY BOTELLA

Plant Genetic Engineering Laboratory, School of Biological Sciences Phone: 07 3365 1128 Email: [email protected]

Characterisation of heterotrimeric G-proteins in plants Heterotrimeric G-proteins are extremely important in humans but very little is known about them in plants. Our lab has established that G-proteins are involved in disease resistance in plants and are also important contributors to yield. We recently discovered new members of the gene family in Arabidopsis and are now investigating their cellular function. The projects involve molecular biology techniques, gene cloning, produce genetic constructs and production and characterization of genetically modified plants. Specific topics include: • Characterization of the role of G-proteins in plant defence. • G-protein control of yield. • Role of G-proteins in cell death. Plant defence against pathogenic fungi Pathogenic fungi cause billions of dollars in loses each year and affect all of the important crops used for human food production. We have recently discovered a number of genes involved in the defence against this type of pathogens and are now devising strategies to produce resistant plants using genetic transformation technologies. The projects involve cloning, molecular characterization of genes and study of a number of transgenic lines with increased disease resistance.


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PROFESSOR PAUL BURN

Director, Centre for Organic Photonics & Electronics (COPE) School of Chemistry & Molecular Biosciences Phone: 07 3346 7614 Email: [email protected]

The Centre for Organic Photonics and Electronics (COPE) is located on floor 9 of the Chemistry Building. The Centre contains state-of-the-art synthesis laboratories, a Class 1000 clean room and a suite of instrument rooms for the characterization of materials and opto-electronic devices. The mission of the Centre is develop ‘organic materials’ that can be used in high performance cutting edge technologies including sensors, solar cells, flat panel displays, plastic electronics, and fuel cells. Honours students working in these areas will learn the key skills of synthetic chemistry and characterization of small and macromolecules, the latter including dendrimers (branched macromolecules) and polymers. In addition, the Honours student will have the opportunity to work with physics colleagues in interpreting the properties of the materials and device performance, which can lead to the design of the next generation of materials. Of particular relevance to Biotechnology students we are offering projects in the area of new sensing technologies. However, we would also be willing to consider students who have an interest in the other areas of research in COPE. Project: Sensors

Sensors play a vital role in many different technologies including the detection of pollution, drugs, and explosives. Recent global events have raised concerns over national security and counter-terrorism measures in civilian areas. In particular, the deployment of hidden explosives over large populated areas requires creative and feasible preventative measures. Currently the most sensitive detectors for explosives are canines. We are therefore interested in developing sensors that are more sensitive and selective than canines, and are using the sensing of explosives as a model system for detecting analytes. The aim is to develop a general sensing technology that can be applied across a broad range of analytes. Most current methods for detecting explosives are slow and the equipment cumbersome. To this end we are developing an explosives sensor based on semiconducting organic materials that will be portable, selective and fast. These materials rely on electron-deficient analytes (explosives) to quench their luminescence, giving a reduction of the normal signal upon binding. For example, dendrimer 3 can detect 1,4-dinitrobenzene and we will be synthesizing and testing new materials against a variety of analytes.


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PROFESSOR ROB CAPON

Institute for Molecular Bioscience Phone: 07 3346 2979 Email: [email protected]

Biodiscovery: From Biodiversity and Bioactives to Biology and Beyond The research interests of my group centre on the detection, isolation, characterisation, identification and evaluation of novel bioactive metabolites from Australian marine and terrestrial biodiversity. These metabolites span all known biosynthetic structure classes including many molecules new to science, and their study requires the use of sophisticated chromatographic, spectroscopic and chemical technologies. Natural products uncovered during our investigations represent valuable new leads in the search for drugs with application in the fields of human and animal health and crop protection, have potential as molecular probes to better interrogate and understand living systems, and could find application as biological control agents. The research group manages an extensive network of collaborators across many scientific disciplines, in industry, academia and government, both in Australia and overseas, which allow it to target such therapeutic indications as infectious and neurodegenerative diseases, cancer, pain, diabetes and obesity, as well as invasive animal and pest control through chemical ecology, and gene activated microbial biodiscovery. Individual research projects can (on enquiry) be negotiated and structured around the following: Natural Products Chemistry: the isolation, and spectroscopic and chemical analysis of, secondary metabolites from marine and terrestrial plants, animals and microbes, with a view to better exploring and understanding “natural” chemical space. Synthetic Organic Chemistry: synthesizing new bioactive natural products, to test and refine novel pharmacophores, to build knowledge of and prioritize new drug lead candidates, with a view to better exploring and understanding “synthetic” chemical space. Microbial Metabolism: learning to better regulate and express silent secondary metabolite gene clusters, to better explore and make use of the full spectrum of “natural” chemical space defined by the microbial genome. Chemical Ecology: to acquire and use knowledge of how invasive pests (ie cane toad) make use of chemistry in the form of defensive secretions and pheromones, and to use this knowledge to develop safe, effective and species selective control solutions.


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PROFESSOR BERNIE CARROLL

School of Chemistry and Molecular Biosciences Phone: 07 3365 2131 Email: [email protected]

RNA interference (RNAi) and gene silencing in Arabidopsis Gene silencing is a highly conserved process in plants and animals, and is of fundamental importance to developmental regulation of gene expression, defence against viruses, transposon silencing, adaptation to environments and genome evolution. Gene silencing is also of immense relevance to biotechnology. We are using Arabidopsis as a eukaryotic model for studying the mechanisms of gene silencing. Intercellular spreading of gene silencing. Remarkably, when gene silencing is triggered in cells of plants and animals, it can spread throughout the organism. The intercellular movement of RNA signals plays a fundamental role in plant development and defence against viruses. We are using a forward genetic approach and map-based gene cloning to elucidate the mechanisms of systemic movement of gene silencing in Arabidopsis. Intron splicing regulates gene expression in Arabidopsis. The role of introns has puzzled molecular biologists since their discovery in 1978. We recently showed that intron splicing protects genes from being silenced in Arabidopsis3. Defective intron splicing has been associated with genetic diseases in both plants and humans. This project aims to identify novel genes and proteins involved in these processes. Genetic engineering of pest resistance in plants based on RNA. RNAi has immense potential for engineering crop resistance to insect pests, and decreasing the use of toxic insecticides that threaten ecosystems and human health. We are expressing RNAi molecules in plants to silence essential insect genes and confer insect resistance.

MicroRNAs involved in high temperature-tolerance in plants. We are using modern molecular techniques and computing to identify miRNAs for high-temperature tolerance in plants. We are using transgenic approaches to modify the expression of these miRNAs to improve high temperature-tolerance in plants.

Selected recent publications: 1. Brosnan et al. (2007) Nuclear gene silencing directs reception of long-distance mRNA silencing in Arabidopsis. PNAS 104, 14741-14746. 2. Gursanscky et al. (2011) Mobile microRNAs hit the target. Traffic 12, 1475-82. 3. Christie et al. (2011) Intron splicing suppresses RNA silencing in Arabidopsis. Plant Journal 68, 159-167.


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DR MARINA CHAVCHICH

Australian Army Malaria Institute Phone: 07 3332 4826 Email: [email protected] Malaria Biology, Malaria Drug Discovery and Resistance In my research laboratory we are studying the malaria parasite, Plasmodium falciparum. Malaria infects approximately 200-300 million people annually which results in 2-3 million deaths. Understanding the biology of the parasite will lead to novel therapeutic options to treat and prevent the disease. In particular, we are focussing our studies on the malarial cell cycle machinery and the respective signal transduction pathways to identify and validate novel malaria drug targets. Additionally, we are interested in understanding the molecular mechanisms of antimalarial drugs and the development of drug resistance. Identification of novel anti-malarial compounds P. falciparum will be cultivated and assayed in an ex vivo/in vitro growth inhibition assay to test compounds for anti-malarial activity. Compounds will be tested against both drug sensitive and resistant parasites to determine a drug resistance index. Selected compounds demonstrating significant activity will be further tested in drug combination studies to find suitable partners that yield a synergistic effect with increased potency. Structure Activity Relationships (SAR) will be evaluated and used to select additional compounds for testing. Compounds will be selected from commercially available libraries and obtained from collaborations with medicinal and natural product chemists. This project will involve dose-response inhibition assays, malaria cultivation, and SAR analysis. Cell cycle control and developmental regulation of the malaria parasite The malaria parasite undergoes multiple rounds of DNA replication in the absence of mitosis in a process known as schizogony. In most eukaryotic cells, DNA replication is followed immediately by mitosis. Cyclin Dependent protein Kinases (CDKs) regulate the progression of the cell cycle and ensure that DNA replication and mitosis occurs in a highly regulated fashion. CDKs are present in the malaria parasite however their role in cell cycle control must be unique in order to regulate schizogony. To further understand the role of malaria CDKs, studies are underway to determine substrate specificity and the regulatory mechanisms of autophosphorylation and the binding of effector proteins. This project will involve protein expression and purification, kinase assays, enzyme kinetics, DNA replication assays, Western blots, immunofluorescence microscopy, two-hybrid protein-protein interaction assays. Pursue the cyclin dependent protein kinases (CDK) as novel malaria drug targets CDKs are drug targets for numerous diseases to include cancer, neurological disorders, cardiovascular disease and recently, parasitic infections. Several malarial CDKs have been developed into 96 well microtiter plate inhibition assays. Compounds will be screened against the malarial CDKs with particular emphasis on Pfmrk. Compounds demonstrating significant inhibitory activity, will be tested against the homologous kinases to deselect compounds that cross react with the human homologs. Compounds will also be tested against the malaria parasite to establish a correlation between inhibition of the CDK and parasite death. Iterative screening, along with a detailed SAR analysis, should identify potent and selective malarial CDK inhibitors. Genetically modified parasites that overexpress Pfmrk, will be used to validate Pfmrk as a drug target. This project will involve protein expression and purification, enzyme kinetics, kinase assays and dose-response inhibition assays.


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PROFESSOR DAVID CRAIK


The Craik lab discovers novel peptides for applications in drug design. Their work has the potential to lead to new drugs for the treatment of a wide range of diseases, including cancer, cardiovascular disease, infectious disease and pain.

Project 1: Novel circular proteins: templates in drug design Until a few years ago circular proteins were virtually unknown, but over recent years we have discovered and structurally characterised a family of circular proteins in plants called the cyclotides. These molecules were originally discovered because of their uses in native medicine as uterotonic agents to aid childbirth and in screening programs of plant extracts against HIV. We have found that the molecules contain an unusual structural motif called a cystine knot in which two disulfide bonds and their connecting backbone form a ring in the structure that is threaded by a third disulfide bond. Combined with a circular backbone this knot makes the cyclotides exceptionally stable, making them potentially valuable frameworks in peptide-based drug design. Cyclotides are resistant to enzymatic degradation and are stable in biological fluids, unlike most peptide-based drugs.

This project involves the discovery and structural characterisation of new cyclotides in plants. We wish to determine the natural structural diversity of the framework so that we can best design novel analogues in which new biological activities are grafted onto the framework. The project will teach skills in natural products isolation and structure determination by NMR spectroscopy. Project 2: Structure-activity relationships in conotoxins: leads in drug design Conotxins are small disulfide rich toxins from the venoms of cone snails. They inhibit a range of ion-channels and are regard as valuable leads in drug design, with four conotoxins currently in clinical trials for various neurological conditions and as analgesic molecules. As part of an ARC funded project we are identifying new conotoxins, as well as synthetically varying known conotoxins with the broad goal of producing novel leads in drug design or neuropharmacological probes. The aim of this project is to determine the structures of these novel conotoxins. The project will teach skills in peptide purification and structure determination by NMR spectroscopy. Project 3: Harnessing plants to produce peptide drugs: drugs in plants We have recently discovered the common machinery that diverse plants use to manufacture stable cyclic peptide frameworks as well as the conserved sequences that allow processing from their precursors. We have performed proof-of-concept work that demonstrates we can genetically modify a reference plant so that it synthesises a protease inhibitor that is a potent lead as a treatment for prostate cancer. Our hypothesis is that we can further enhance this system to produce low-cost synthesis of tailor-made drugs in seeds through genetic engineering. The technology developed from this project will allow stable peptide drugs to be manufactured at low cost and, as a more “organic” drug source, has the potential to improve patient compliance as well as be adaptable to production systems in third-world nations. This project will teach skills in plant genetic transformation, peptide analysis, and genetic analysis.



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PROFESSOR JAMES DE VOSS

School of Chemistry & Molecular Biosciences Phone: 07 3365 3825 Email: [email protected]

My group is concerned with biological and synthetic chemistry and in particular with the application of chemical principles to the understanding of biological processes. Most projects are a blend of disciplines in bio-organic chemistry: synthesis, structure determination, molecular biology, protein purification. A range of techniques is employed, ranging from the biochemical (e.g. PCR, gel electrophoresis) to the chemical (e.g. NMR, HPLC, GC/MS). The following areas illustrate the research in my laboratory but the exact project will be determined by the student’s interests. Project 1: Cytochromes P450: P450s catalyse an amazing variety of oxidative transformations, ranging from simple alkene epoxidation all the way through to oxidative C-C bond cleavage. They are of interest as they (i) are often unique enzymes in a biosynthetic pathway and as such represent new targets for chemotherapeutic agents or (ii) are extremely efficient catalysts that offer the potential of developing tailored oxidative catalysts for synthetic transformations. We are interested in understanding the mechanism of action of a number of P450s. One example is CYP61, a unique P450 involved in steroid biosynthesis in fungi and other pathogenic organisms. As such it represents a potential target for novel chemotherapeutics. CYP61 catalyses an unusual reaction for a P450, namely the dehydrogenation of an alkane to an alkene. However, essentially nothing is known about the exact structure of the substrate, the stereochemistry of the reaction or its mechanism. Projects in this area will involve the synthesis of mechanistic probes, the analysis of the products of enzyme-catalysed reactions, characterisation of enzyme mutants and design and synthesis of inhibitors.

Project 2: Constituents of Medicinally Used Herbs: Whilst herbal medicines are widely used and have a long history of such use, their chemical constituents are often poorly characterised. In collaboration with a local company we have embarked

upon a program of phytochemical characterisation of a number of therapeutically prescribed herbs. The results have been surprising with a number of previously unknown compounds isolated from supposedly well-characterised species. This project would involve the isolation, chromatographic purification and structure determination (especially employing 1D and 2D nmr) of the chemical constituents of selected herbs. The structures of some recently isolated compounds are given below. Relevant Recent Publications 1. Slessor, Kate E., Farlow, Anthony J., Cavaignac, Sonia M., Stok, Jeanette E., De Voss, James J. Oxygen activation by P450(cin): Protein and substrate mutagenesis Arch. Biochem. Biophys. 2011, 507 154-162. 2. N. J. Matovic, J. M. U. Stuthe, V. L. Challinor, P. V. Bernhardt, R. P. Lehmann, W. Kitching and J. J. De Voss The Truth about False Unicorn (Chamaelirium luteum): Total Synthesis of 23R,24S-Chiograsterol B Defines the Structure of the Major Saponins from this Medicinal Herb Chem. Eur. J. 2011 17, 7578-91.



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DR ANNETTE DEXTER

Australian Institute for Bioengineering & Nanotechnology (AIBN) Phone: 07 3346 3199 Email: [email protected]

Research area: Designer peptides for biomedical and industrial applications Designer peptides are attractive building blocks for preparation of novel functional nanomaterials. Peptides offer stimuli-responsiveness, biocompatibility, predictable folding and capacity for sustainable production. By employing and modifying a key structural motif of native proteins, the amphipathic alpha-helix, we have developed short designer peptides that show promise as responsive hydrogels for wound healing, tissue engineering and drug delivery or, in a separate class, as environmentally-friendly switchable surfactants. Dr Dexter is a co-founder of UQ start-up company Pepfactants Pty Ltd, and is involved in commercialization of peptides as “green” surfactants as well as biocompatible gelling agents. Project 1: Peptide hydrogels for burn healing Burns represent a major category of accidentally acquired injury, with over 130,000 injuries in this class in Australia each year. Currently, all children who sustain deep dermal burns will heal with unsightly scars. Scarred areas fail to grow with the child and often cause contractures that require repeated surgery. The scarred tissue is weaker than normal tissue and is prone to drying and ulceration. Pressure garments and silicone sheets are the only proven methods to reduce scar formation, however they must be worn for at least a year and the results are often disappointing. Prevention of scarring following deep burns is thus an important medical goal with long-term consequences for quality of life of burn victims. We are developing peptide hydrogels as advanced wound dressings with the potential to accelerate re-epithelialisation of burn wounds to prevent scarring. An Honours project is available in formulating and testing hydrogels for the treatment of burn wounds. Project 2: Peptides as surfactants for eco-friendly industrial fluids Industrial fluids are lubricating and cooling fluids extensively used in industrial machining operations. As currently formulated they represent both an occupational health and safety hazard for machine operators, and a waste disposal problem at the end of their lifecycle. Oil-in-water industrial fluid emulsions are usually formulated with petrochemical surfactants that can break down to give hazardous sulfhydryl gases, cause painful skin lesions on prolonged contact, and form emulsions that are difficult to separate for the disposal of oil and water phases. We are currently investigating the use of peptides as alternate surfactants for industrial fluids, in conjunction with a major industry partner. The peptides offer both lower toxicity as sulfur-free and biocompatible surfactants, and a capacity for emulsion switching to allow clean separation of oil and water at the end of the emulsion lifecycle. An Honours project is available in formulating and testing cutting fluids for lubrication in metal-working and recyclability of the functional components. Project 3: Bioproduction of peptides as hetero- or homoconcatemers The adoption of peptides for materials applications, either in the biomedical or industrial space, will depend on methods for low-cost, large-scale production. Currently, most peptides tested for drug or other applications are produced by solid-phase synthesis (a costly method with high environmental impact) and are subsequently purified by expensive chromatographic methods. While short peptides can be produced in bacterial hosts by fusion to a carrier protein, this approach has poor efficiency, as most of the product obtained (>80%) is carrier protein rather than the target peptide. We recently developed a novel method for expressing ionic surfactant peptides, by using heteroconcatemers of oppositely-charged peptides to form a coiled-coil miniprotein. The resulting protein is stable to heat and proteases and can be purified by simple precipitation steps. We are now seeking to extend this approach to gel-forming peptides, to facilitate the use of such peptides in biomedical applications. An Honours project is available in the design, expression and downstream processing of a gelling peptide for biomedical use.



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ASSOCIATE PROFESSOR PAUL EBERT

School of Biological Sciences Phone: 07 3365 2973 Email: [email protected]

Project 1: Functional genomics of ageing Despite a significant increase in human life expectancy, old age is still characterised by physiological changes that manifest themselves as age-related diseases. The ultimate goal of this research is to increase the disease-free lifespan of individuals. We approach this problem in two ways: The first is to investigate the ageing process itself, whereas the second is to model disease of old age and to test the effect of drug therapies. We are using the genetic model organism, Caenorhabditis elegans, as it is the leading model organism for lifespan research. We have identified a novel longevity gene and are now determining its mode of action and potential interaction with diseases of old age. The project involves microarray analysis, targeted epigenetic gene suppression, genome sequencing, bioinformatics and genetics.

Project 2: Cloning of phosphine resistance genes from pest insects: Stored grain is protected from insect pests by fumigation with phosphine, but some insects are now resistant to 600 times the normal lethal dose of phosphine. Several new fumigants have been proposed, but their modes of action and interaction with other fumigants and with phosphine resistant insects is unknown. This project will be carried out in collaboration with the Queensland Department of Agriculture, Fisheries & Forestry and will characterize these new fumigants to help lead the grains industry into a new

future. This project will involve toxicology testing, genome sequencing, bioinformatics and perhaps some work with C. elegans.



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ASSOCIATE PROFESSOR DARRYL EYLES

Queensland Brain Institute Phone: 07 3346 6370 Email: [email protected]

Studies in our lab relate the major epidemiological findings in schizophrenia with how the brain may be altered during development. Projects relate directly to the epidemiology implicating certain risk factors during gestation that correlate with increased schizophrenia in offspring. One prominent risk factor we have established is developmental vitamin D deficiency. Project: The effect of maternal vitamin D deficiency on dopamine neuron ontogeny The student would examine the brains of embryonic animals from vitamin D deficient Dams. The student would study the timing of the expression of crucial dopaminergic transcription regulators in the developing mesencephalon. The student would also conduct in vitro experiments examining the activation status of the receptor for vitamin D in these same cells. These studies will help to inform the larger structural and behavioural picture emerging in this model strongly implicating dopaminergic dysfunction. Data from both these studies could have considerable public health implications regarding preventative measures in utero for developmental diseases such as MS and schizophrenia! Students interested in honours projects or higher degrees should contact me. I can be found in the Queensland Brain Institute, The University of Queensland, Brisbane, Qld 4072, Australia.



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PROFESSOR DAVID FAIRLIE


Our research programs ( http://fairlie.imb.uq.edu.au/ ) link chemistry to biologically important problems related to pathogenesis and treatment of disease. Students develop expertise in organic, medicinal or biological chemistry; learning principles of molecular design, synthesis (solid and solution phase, combinatorial chemistry, microwave-assisted), structure determination (2D NMR spectroscopy), or biological properties through interactions with proteins. Outcomes are new structures, reactions, mechanisms, enzyme inhibitors, protein agonists/antagonists, and new drugs. Each Hons student (http://fairlie.imb.uq.edu.au/researchers.php?id=24; id=22) produces significant publishable results from their project (e.g. Synthesis of antagonists for inflammatory GPCRs; Design and Synthesis of anti-inflammatory phospholipase inhibitors; Evaluation of nociceptin analogues as potent agonists and antagonists of Opioid Receptors; Metal clips for fixing peptides in alpha helices). Hons projects are tailored around the interests of students. Some representative projects are: Project 1: Antagonists of human G protein coupled receptors Many human diseases start by proteins acting on surfaces of cells. We wish to synthesize small organic compounds that bind tightly to cell surfaces and prevent or mimic such actions, thereby regulating intracellular signaling pathways associated with cancer, inflammatory conditions, cardiovascular and Alzheimer’s diseases. This project involves 90% organic synthesis (using solution and solid phase techniques, NMR spectroscopy, combinatorial and microwave synthesis methods) and collaboration with other members of the group who will undertake most of the biology, unless the student also wishes to learn biology. (For background see: Chem Rev 2007, 107, 2960-3041). Project 2: Inhibitors of Proteases Proteolytic enzymes are involved in the synthesis, turnover and degradation of all proteins and are validated therapeutic targets in human diseases. This project will design potent and selective inhibitors of proteases associated with inflammatory diseases. Either a cysteine protease or a serine protease will be the enzyme target. The project involves synthetic chemistry, collaboration with a computer modeller, and willingness to screen compounds every 2-3 weeks in a 2 hour bioassay. Resulting compounds will be anti-inflammatory agents. Background (J. Med. Chem. 2000, 43, 305). Project 3: Protein Surface Mimics We have a range of projects available that are directed towards downsizing a bioactive region of a protein to a small organic molecule that can structurally and functionally mimic key protein surfaces. Background reading: Shepherd NE et al; Modular Alpha Helical Mimetics With Antiviral Activity Against Respiratory Syncitial Virus. J. Am. Chem. Soc. 2006, 128, 13284-13289. Shepherd NE et al; Left- and Right-Handed Alpha-Helical Turns in Homo- and Hetero-Chiral Helical Scaffolds. J Am Chem Soc. 2009, 131, 15877-15886. Ma MT et al; Metal Clips That Induce Unstructured Pentapeptides To Be Alpha Helical In Water. J Am Chem Soc 2009, 131, 4505-4512. For more information: contact David or visit http://fairlie.imb.uq.edu.au/


http://fairlie.imb.uq.edu.au/

http://fairlie.imb.uq.edu.au/researchers.php?id=24

http://fairlie.imb.uq.edu.au/


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ASSOCIATE PROFESSOR CAMILE FARAH

Group Leader, Oral Oncology Research Program University of Queensland Centre for Clinical Research (UQCCR) Phone: 07 3346 6030 Email: [email protected]

PROGRAM MEMBERS:Academic & Research Staff • Associate Professor Camile Farah (Group Leader) • Dr Pauline Ford (Senior Lecturer) • Dr Andrew Dalley (Postdoctoral Research Officer) • Mr Anthony Chan (Histology Technician). Adjunct Academic Staff • Dr Martin Batstone (Maxillofacial Surgeon, RBWH) • Dr Borjana Simanovic (Visiting Dentist) • Dr Maurie Stevens (ENT Surgeon, RBWH) • Dr Colin Ades (QML Pathology) Research Higher Degree Students • Dr Ahmad Abdul Majeed (PhD), • Dr Glenn Francis (PhD) • Dr Phan Nguyen (PhD) • Dr Maryam Jessri (PhD) • Anthony Crombie (MPhil) • Ms Kelsey Moore (MPhil) • Ms Fatima Dost (MPhil). Concurrent BDSc/MPhil Students • Ms Kristine Allen • Mr Nirav Bhatia • Mr Sean Currie • Ms Yasitra Lallaq • Ms An Vu • Ms Jennifer Wu • Ms Keziah John • Ms Brie Kwon • Mr Bing Lee • Dr Ian Housego • Dr John Webster Honours Students • Mr Aidan Major, Mr Luke Pitty PROGRAM SUMMARY: The Oral Oncology Research Program leverages work regarding various bio-markers of oral cancer and oral epithelial dysplasia which are either unique to the oral mucosal situation or shared across malignancies in other sites. The program leverages a range of novel technologies, including optical fluorescence imaging and narrow band imaging, to be able to diagnose oral cancer at its earliest stages, thus allowing early forms of treatment to be applied with maximal effect. The program also investigates the role that cancer stem cells play in the propagation and recurrence of cancerous and pre-cancerous lesions. The underlying premise of this program looks at creating a molecular signature for pre-cancerous conditions that can be used as a diagnostic test to either replace or supplement standard histopathological interpretation of oral epithelial dysplasia and oral squamous cell carcinoma. To complement the program’s work on the biological mechanisms of oral cancer, we are undertaking projects to examine oral pre-cancerous conditions at the population level. Clinical and epidemiological studies of defined at-risk populations are underway which will determine the burden of oral mucosal disease as well as the relative importance of a range of risk factors for these groups. This information is fundamental to planning for oral health services and public health interventions which are appropriate and cost effective. The work of the group is undertaken at the UQ Centre for Clinical Research based at the Royal Brisbane & Women’s Hospital at Herston. This program is funded by grants from the National Health & Medical Research Council, Cancer Australia, Cancer Council Queensland, Queensland Government Smart Futures Fund, RBWH Foundation, and the Australian Dental Research Foundation. The group has collaborations with Agilent Technologies, Life Technologies, Olympus Australia, Colgate-Palmolive Australia, and the Institute for Urban Indigenous Health. AVAILABLE PROJECTS: Project 1: Molecular profiling of cancer stem cell / Project 2: miRNA expression in oral epithelial dysplasia



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ASSOCIATE PROFESSOR VITO FERRO

Deputy Director, Biotechnology Program School of Chemistry & Molecular Biosciences Phone: 07 3346 9598 Email: [email protected]

My research interests encompass carbohydrate chemistry and medicinal chemistry, with a focus on the synthesis of compounds to probe and/or inhibit carbohydrate-protein interactions involved in disease processes. Of particular interest is heparan sulfate (HS) and the development of HS-mimetics as potential drugs for cancer and various other diseases. Previous work in this area resulted in the discovery of PG545, a potent inhibitor of angiogenesis and metastasis that recently entered Phase I clinical trials in cancer patients.

1. Development of a fluorometric assay for heparanase Heparanase is a glycosidase that cleaves HS in the extracellular matrix and facilitates metastasis of tumour cells and vascular remodelling associated with angiogenesis. PG545 is an example of a heparanase inhibitor with potent in vivo activity in metastatic and angiogenic models. Despite the advancement to clinical trials of inhibitors, heparanase research has been limited by the lack of a simple and robust assay for enzymatic activity. This project aims to address the situation by the synthesis of novel fluorogenic substrates for heparanase. 2. Synthesis of pharmacological chaperones for lysosomal storage diseases Lysosomal storage diseases (LSD) are caused by mutations in enzymes that degrade polysaccharides such as HS, resulting in the accumulation of undegraded substrate in the lysosomes of cells. Some patients may be treated with enzyme replacement therapy. Unfortunately, the replacement enzyme cannot cross the blood-brain barrier and thus cannot treat the neurological symptoms associated with severe cases. The aims of this project are to develop small molecules for the treatment of LSD, which unlike enzymes, are capable of crossing the blood-brain barrier and thus may offer relief of neurological symptoms. The compounds are designed to act as “chaperones” to protect the defective enzyme from degradation and restore enzyme activity to sufficient levels to alleviate symptoms. 3. Glycosylated liposomes for targeted delivery of siRNA Targeted delivery to a specific cell type is desirable to improve the effectiveness and specificity of siRNA for gene silencing. The aim of this project is to generate specifically glycosylated liposomes that will enable delivery of siRNA to particular cell types possessing receptors for these glycans. 4. Synthesis of inhibitors of virus-cell attachment Many viruses, including HSV and HIV, use HS as an entry receptor or co-receptor. This project will focus on the synthesis of novel HS mimetics that inhibit virus-cell attachment and possess virucidal activity.



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DR DONALD GARDINER CSIRO Plant Industry / Queensland BioScience Precinct, UQ-St. Lucia Campus Phone: 07 3214 2370 Email: [email protected] FUSARIUM PATHOGENESIS IN WHEAT The lab is currently researching mechanisms of pathogenicity and virulence in fungal pathogens. We work with pathogens that cause crown rot and head blight disease of wheat and also pathogens that cause Fusarium wilt disease in a number of plant species. Students in the lab will be given their own project under the supervision of a more experienced lab member (Jason Carere, a postdoctoral fellow [email protected]) with the hope of producing publishable results. A position is currently available on the current project: Characterization of a hydrolase involved in defence compound degradation This hydrolase from Fusarium pseudograminearum has been shown to be important for pathogenesis in wheat. The project involves the expression and purification of this protein to determine possible substrates which it acts on in planta. This will be accomplished through the use of enzymatic assays and x-ray crystallography. This work will improve our understanding of the chemicals plants produce to protect themselves and the mechanism by which pathogens evade those defences. If you have any questions or would like further information please contact Don or Jason by email.



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PROFESSOR IAN GENTLE

School of Chemistry & Molecular Biosciences ARC Centre of Excellence for Functional Nanomaterials Phone: 07 3365 4800 Email: [email protected]

Research in the Surface Chemistry Group is concerned with the self-assembly of materials at interfaces, a field of research which encompasses thin film methods and other surface processes. Thin film techniques have important technological applications in the construction of devices with useful electronic, optical or optoelectronic properties, and interfaces are also important to many biological systems. Methods of characterisation used include grazing incidence X-ray and neutron scattering and spectroscopy (facilities at the OPAL Neutron Source in Sydney, the Australian Synchrotron in Melbourne or overseas facilities are normally used for this purpose), X-ray reflectometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), depending on the project. At UQ, the facilities for characterisation of thin films and materials (in the Centre for Microscopy and Microanalysis) are state of the art. These include a $1.1M imaging XPS, a Digital Instruments NanoScope scanning probe microscope, an Anton Paar Small Angle X-Ray Scattering instrument and two Bruker X-ray diffractometers. New Directions towards High Energy Supercapacitors: Graphene-based Multifunctional Electrodes Supercapacitors with high power density and long life span are the most promising solutions beyond lithium ion batteries to power electric vehicles, transportation and electronic devices. However, the low energy density of supercapacitors is a major impediment to their development. This project aims to address the materials and device challenges in high energy supercapacitors, and to propose guidelines for electrode design principles, materials synthesis methodology and device configuration strategy. The core concept of this research is to optimize the performance of graphene-based electrodes by tailoring nanoporous structure, lattice dopants, surface functionalities and mechanical properties, and most crucially, to understand the basic electrochemical processes. Specific objectives are to: •Synthesise heterogeneous graphene-based nanosheets with desirable nanoporosity, lattice dopants and surface functionality; •Assemble multifunctional graphene-based electrodes combining electrochemical reactivity and mechanical flexibility; •Understand the mechanisms of electrochemical interfacial reactions and inner-pore ion transport to optimize overall performance of the graphene-based multifunctional electrodes. This project will be carried out in collaboration with Dr Da-Wei Wang. It will involve extensive use of chemical and surface synthetic techniques, structural characterisation by advanced methods described above, combined with electrochemical measurements. Depending on the rate of progress, there may be the opportunity for prototype supercapacitor device construction using the new materials developed in the project.



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PROFESSOR ROBERT G GILBERT

Centre for Nutrition & Food Sciences School of Chemistry & Molecular Biosciences Phone: 07 3365 4809 Email: [email protected]

Biosynthesis-structure-property relations for starch and glycogen Starch provides more than half the world population’s calorific intake; glycogen is our body’s glucose buffer. These are at first sight simple homopolymers of glucose, but their structure spans many levels of complexity, with features ranging from nm to mm. These structural features strongly influence nutritional value for humans, and how well glycogen is effective in controlling blood sugar (and hence propensity to diabetes). In synthetic polymer science and technology, the paradigm for understanding material properties, and producing materials with improved properties, is well established as synthesis controls structure controls properties. The equivalent has been impossible for starch and glycogen: one changes the genetics (biosynthesis) to try to obtain cereals with desirable properties—better digestibility for managing and reducing obesity, diabetes and colo-rectal cancers—and drug targets for diabetes through glycogen synthesis enzymes. This project will greatly expand current knowledge, through our unique experimental and theoretical tools, to examine the structure of these polymers and then to relate the structural features to both biosynthesis and to properties. Examples of available projects : Project 1: Kinetics of enzymatic degradation of starch and glycogen This project will examine the rates at which starch is degraded by enzymes in human digestion, and how glycogen in different organs is degraded to provide blood sugar when needed physiologically. This project will examine the kinetics of these processes in vitro, to shed light on the corresponding in vivo processes which are of major importance in controlling obesity and diabetes. Project 2: Genetics/structure relations: experiment There is no detailed knowledge on which genes control the extent of starch/glycogen branching at the micro- or nano-structural level. There is also little information on the effects of environmental conditions on the differential expression of the genes, nor the extent of genetic variation in these gene families. This project will examine polymer structures in varieties obtained and characterized by modern techniques in molecular biology and biotechnology to link the genome (gene) to phenome (structure) with reference to growth conditions. Interpreting these data will yield information on the detailed mechanisms by which enzymes of specific structure control particular aspects of starch structure. Molecular structural differences between type-2-diabetic and healthy glycogen. MA Sullivan, J Li, C Li, F Vilaplana, D Stapleton, AA Gray-Weale, S Bowen, L Zheng, RG Gilbert. Bio¬macro¬¬¬molecules 12 1983 (2011); Molecular weight distributions of starch branches reveal genetic constraints on biosynthesis. AC Wu, RG Gilbert. Biomacromolecules, 11 3539 (2010); Amylose content in starches: towards optimal definition and validating experimental methods. F Vilaplana, J Hasjim, RG Gilbert. Carbohydrate Polymers 88 103 (2012)



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PROFESSOR ELIZABETH GILLAM


Catalytic promiscuity and artificial evolution of P450 enzymes The cytochromes P450 are one of the most functionally versatile groups of enzymes known. They carry out diverse roles in Nature because they can catalyse an extraordinary range of chemical transformations, ranging from aromatic/aliphatic hydroxylation and heteroatom oxidation, to group transfers, ring expansion/contraction, coupling reactions, and C-C bond cleavage. This makes them ideal starting materials for engineering designer biocatalysts for difficult chemical reactions. Our group is interested in finding out how P450s work and how they can be made to work better. Project 1: Artificial evolution: better, faster, more specialised P450s can accelerate drug development and clean up environmental pollutants We are using artificial (or directed) evolution to generate libraries of mutants from naturally-occurring P450 forms with the aim of engineering catalysts with properties enhanced by orders of magnitude over those found in naturally occurring enzymes. Project 2: What determines the catalytic promiscuity of P450s? Collectively a handful of P450s metabolise ~ 95% of all drugs to which humans are exposed as well as innumerable environmental chemicals. This is a truly exceptional variety of substrates. Our aim is to determine how these enzymes can show such extreme catalytic promiscuity using a range of biophysical and molecular techniques. Project 3: P450 Nanodiscs for biosensors (with Prof. Paul Bernhardt) Since P450s respond to such a variety of different substrates they are well suited for use as biosensors to detect trace environmental contaminants, drugs and other chemicals. We will formulate P450s into nanodiscs – very small protein-bounded lipid bilayer discs – to characterise their electrical properties by protein electrochemistry. Project 4: Structural signatures of P450s (with Dr. Mikael Boden) We are using bioinformatics tools to explore the essential sequence and structural features underpinning all ~12000 known P450s so as to determine how P450s work. Students doing Honours in the Gillam lab gain experience in cutting-edge techniques such as artificial evolution of proteins, high throughput screening, protein design and preparation of nanodiscs as well as fundamental methods of molecular cloning, protein chemistry, enzymology and metabolite analysis. Our research suits students in biochemistry/molecular biology, chemistry, biotechnology, or bioinformatics who are interested in discovering how enzymes work and how to engineer them to provide clean green alternatives to chemical processes.



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PROFESSOR JEFF GORMAN

Queensland Institute of Medical Research (QIMR) Phone: 07 3845 3669 Email: [email protected]

Protein Discovery / Proteomics The QIMR Protein Discovery Centre is arguably the most advanced infrastructure centre in Australia for the analysis of chemical features of proteins and documentation of proteomes of cells, organisms and tissues. We are particularly interested in the interactions between host cells and infectious organisms as reflected by dynamic changes in the protein repertoires (proteomes) of cells infected by viruses. We are also interested in interactions between proteins required to initiate, sustain and perpetuate viral and parasitic invasion of cells. The ultimate aim of our work is to develop a better understanding of interactions between infectious organisms and host cells to develop therapeutic interventions for serious human diseases such as viral respiratory infections and malaria. Our projects involve extensive collaborations with leading Australian and international scientists. Evasion of host cell innate immunity by respiratory syncytial virus: Respiratory syncytial virus (RSV) is a serious pediatric respiratory pathogen and is increasing recognised as an important pathogen of geriatrics. RSV is a master of evasion of the host cell antiviral response. One specific viral gene product, non-structural protein 1 (NS1) of RSV contributes substantially to blocking the host cell antiviral response. In this project we are using a combination of reverse viral genetics and proteomics to determine the mechanism(s) by which NS1 exerts its influence over the infected cell. This project involves collaboration with Dr Peter Collins and his group from the US National Institutes of Health and Dr Kirsten Spann from UQ who contribute molecular virology expertise. Click chemistry probes of complex macromolecular assemblies: This project involves the development of a diverse range of click chemistry probes to label the exterior of macromolecular assemblies. These probes are designed to probe the distributions of protein domains within membrane assemblies and to obtain low resolution structural information on externally disposed domains. These probes will be applied to help understand the interactions of viruses and parasites with host cells and the structures of proteins on the surfaces of these infectious agents. This project involves collaboration with Dr Ross McGeary of UQ and scientists from QIMR, including Dr Kathy Andrews (malaria parasites), Dr Greg Anderson (iron transport) and Dr Nathan Subramaniam (iron transport). Viral proteomics: Using proteomic techniques, we and others have shown that viruses often package cellular proteins into mature virions. These cellular proteins are often from molecular machines that viruses use during trafficking in and budding from the host cell. This project aims to investigate the variation in cellular proteins packaged by different viruses in order to ascertain the likely mechanisms by which different viruses interact with host cell molecular machinery. Post-translational modifications of malarial proteins: Malaria transitions through a number of different forms during its lifecycle. This project aims to examine the post-translational modifications to malarial proteins, particularly phosphorylation, during these transformations as a way of defining these processes at a molecular level. This is a collaboration with Dr Don Gardiner and his group at QIMR.



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PROFESSOR PETER GRESSHOFF

ARC Centre for Integrative Legume Research Phone: 07 3365 3550 Email: [email protected]

Plants possess stem cells that have the ability to differentiate into multiple cell types. The signals controlling this process are critical in the developmental biology of plant growth (see Beveridge et al, 2007; Curr. Topics in Plant Biology). We are looking at one specific stem cell cluster called the nodule meristem. These develop into new organs. We ask: what are the genes responsible for that? How do they interact? What are the signals and the receptors? How does physiology interact with gene expression? We offer three cutting edge projects for top students willing to learn functional genomics and plant biotechnology. The research is carried out within the ARC Centre of Excellence for Integrative Legume Research (CILR), and interested students should visit the website www.cilr.uq.edu.au. Project 1: Molecular signalling during stem cell differentiation and lateral organ differentiation in legumes such as soybean, Lotus japonicus and Medicago truncatula): The project utilises our increasing understanding of long distance regulation of plant organ induction and differentiation. Critical genes controlling nodulation (GmNFR1, GmCLE80, GmNARK) have now been cloned and characterised. We are starting to understand what molecular signal activates the receptor kinase, what are the down-stream signals and responses (Kinkema and Gresshoff, 2008, Mol. Plant Microbe Interactions), what are its ligands, what proteins are phosphorylated? (See Miyahara et al, 2008, J. Biol. Chemistry). We recently discovered new peptide signal molecules that may act like hormones (Gresshoff et al, 2009, Plant Signalling & Behaviour). We are testing the similarities of these regulatory circuits with those controlling stem cell proliferation (i.e., GmCLV1, GmWUS, GmCLV2, and GmCLV3). Supervisors: Professor Peter Gresshoff, Dr Arief Indrasunumar, Dr Jacqui Batley and Dr Brett Ferguson. Project 2: Biotechnology of sustainable biofuel (biodiesel) production from the legume tree Pongamia pinnata: Biofuels are essential for our future. We have initiated a biofuel program using biotechnology and genetics coupled with physiology and biology to develop a scientific basis for that growing industry. We are focusing on a legume to eliminate the energy and environmental costs of nitrogen fertiliser. Our plant of choice is a legume tree Pongamia pinnata (see Scott et al, 2008, BioEnergy Research) from which oil-rich seeds are harvested each year. Already industry such as ORIGIN Energy, Pacific Renewable Energy, and BioEnergy Research, are interested in this biotech project. Several projects exist dealing with the optimisation of nitrogen fixation, seed storage protein gene promoters, gene expression analysis, etc. Supervisors: Dr Paul Scott, Professor Peter Gresshoff, Dr Bandana Biswas, and Dr Qunyi Jiang and. Project 3: Molecular physiology and biotechnology of ethylene regulation of nodulation and lateral root development in the model legume Lotus japonicus: This legume has a small genome, is easily transformed, and has yielded many valuable mutants. Forward and reverse genetics are available. We have produced the world’s first transgenic legumes expressing an Arabidopsis ethylene receptor gene (see Lohar et al, 2009, Annals of Botany; Gresshoff et al, 2009, Plant Signaling & Behaviour). Furthermore we have isolated both ethylene and ABA insensitive mutants in this model legume. The ethylene insensitive plants have altered physiological properties including increased nodulation, decreased lateral root formation and slowed maturation. The ABA insensitive mutant BEYMA shows extreme wilting because of an inability to regulate stomatal openings (see Biswas et al, 2009, Molecular Plant). Cloning of the BEYMA gene is an immediate goal. We are attempting to eliminate some of the negative effects by using tissue-specific promoters in transformation. Grafting is needed to evaluate the role of shoot vs. root in the physiological stress responses. Supervisors: Professor Peter Gresshoff, Dr Bandana Biswas and Dr Qunyi Jiang



46

DR ULRIKE KAPPLER


Regulation of gene expression Regulation of bacterial sulfite oxidation – a novel role for extracytoplasmic function (ECF) sigma factors. Enzymes & their role in bacterial physiology Do metalloenzymes support virulence of human pathogens? Case study: Haemophilus influenzae Molybdenum enzymes. Friend or Foe? – Metabolic interactions between Streptococcus pneumoniae and Haemophilus influenzae. Environmental microbiology & applications Some like it alkaline – Can we use alikaliphilic sulfur oxidizers to treat sulfur pollution? Co-supervision with Prof. Gordon Southam: “The growth of gold nuggets” – bacterial degradation of thiosulfate gold complexes. If you find these topics interesting, but would like to work on other aspects of the projects, please contact me – this list is not comprehensive and additional projects are available.



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PROFESSOR MARK KENDALL

Australian Institute for Bioengineering & Nanotechnology (AIBN) Phone: 07 3346 4203 Email: [email protected]

DR SIMON CORRIE

Australian Institute for Bioengineering & Nanotechnology (AIBN) Phone: 07 3346 4209 Email: [email protected] Web: http://www.aibn.uq.edu.au/simon-corrie

Delivering vaccines and sampling diagnostic molecules through the skin The outermost layers of our skin contain a rich and untapped source of immune-sensitive cells and blood-borne biomarkers. We are developing new technologies to deliver vaccines to, or extrac diagnostic biomarkers from, these outer skin layers. Our group is a multidisciplinary mix of scientists (chemists, immunologists, virologists, vaccinologists) and engineers (mechanical, civil, chemical) who together bring a diverse array of expertise and skill sets to solve important technology problems and to learn more about the biology, immunology and mechanical properties of the skin. Our laboratory facilities include a mechanical design suite, a multi-photon microscopy system, a range of immunological and molecular assays and material fabrication and surface modification facilities. We also use the facilities of the Australian National Fabrication Facility QLD node (ANFF-Q – level 2 AIBN), UQ’s Centre for Microscopy and Microanalysis (CMM – especially SEM, XPS) and the University of Queensland Biological Resources (UQBR) animal housing facility (level 6, AIBN to support our manufacturing, analytical and pre-clinical testing needs. We currently have Honours project opportunities in both vaccine delivery and diagnostics projects. These projects include: • Engineering, expressing and testing novel vaccine formulations on patches in comparison to standard intramuscular injections • Engineering, expressing and testing new diagnostic capture probes for improved diagnostic performance, based on sensitivity or assay simplicity • New surface chemistry approaches to improve capture and release of biomolecules from patch devices • Microfluidic approaches to detect key biomarkers extracted from skin Projects are available for a wide array of skill sets. Students with a background in biotechnology, molecular biology or physical/inorganic chemistry should apply. Skills gained will include molecular biological techniques (ELISA/PCR), surface chemistry, microfabrication and pre-clinical animal testing of devices (optional). Opportunities exist for students to continue their work, or start new projects, in MPhil or PhD programs.



http://www.aibn.uq.edu.au/simon-corrie


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PROFESSOR ALEXANDER KHROMYKH

RNA Virology Laboratory School of Chemistry & Molecular Biosciences Phone: 07 3346 7219 Email: [email protected]

RNA virology laboratory study molecular mechanisms of virus RNA replication and virus-host interactions with the main focus on the West Nile virus (WNV) and more recently on Chikungunya virus. WNV belongs to Flaviviruses, a group of highly pathogenic positive strand RNA viruses causing major outbreaks of potentially fatal diseases and affecting more than 50 million people each year. Chikungunya virus is a member of Alphaviruses and has recently caused large outbreaks of devastating arthritis disease in Reunion Island and Asian countries. We are aiming at a better understanding of how these viruses replicate in the host and cause disease, which will help in the development of antiviral drugs. In addition, we develop and evaluate vaccine candidates to prevent infection and outbreaks. The following projects are available: Role of Small Subgenomic RNA in Flavivrus Pathogenicity. We recently identified a small subgenomic RNA produced from the 3’ untranslated region of the viral RNA in cells infected with a variety of flaviviruses. This subgenomic flavivirus RNA (sfRNA) is the product of incomplete degradation of genomic RNA by cellular ribonucleases and is required for viral response. We will elucidate the function of sfRNA in the viral life cycle and identifyi cellular and viral interaction partners of sfRNA. Virulence Determinants and Host Innate Immune Response to West Nile Viruses. We have shown previously that WNV is able to evade innate immune response with more virulent strain able to do it more efficiently. There are a number of projects available in collaboration with leading overseas groups (M Diamond, USA; M Gale, USA; and S Akira, Japan) as well as local virologists (Roy Hall, SCMB) which will focus on the mechanisms by which pathogenic (New York 99) and non-pathogenic (Kunjin) strains of WNV interact with the host innate immune response and how these interactions determine outcome of infection. KUN Virus DNA-Based Vaccine against Pathogenic Flaviviruses. We recently published the development of a highly effective DNA vaccine against WNV which involves the production of single round infectious particles and has been shown to induce high antibody levels in mice and horses. The project will continue in collaboration with Dr. Roy Hall at SCMB and Dr. Andreas Suhrbier at the QIMR to extend the technology to development of vaccines against other medically important flaviviruses, dengue and Japanese Encephalitis. The role of miRNAs in Flavivirus-Mosquito Host Interactions. In collaboration with S Asgari (SBMS) we have identified a first miRNA produced by WNV and have shown that it targets a transcription factor in mosquito cells that is essential for virus replication. This project is aimed at further investigations of the role of WNV-induced/produced cellular and viral microRNAs (miRNA) in determining the outcome of virus infection in mosquito vector. Innate immune response to Chikungunya virus. This project is a collaboration with Andreas Suhrbier (QIMR) and is focused on understanding how the innate immune response to this infection relates to virus-induced disease. Using mouse model of the disease developed at QIMR the studies will employ a wide range of mouse strains deficient in expression of various factors involved in innate immune response and cell lines derived from them to identify host factors involved in response to Chikungunya virus infection and in the development of virus-induced arthritis



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PROFESSOR GLENN KING

Institute of Molecular Biosciences Phone: 07 3346 2025 Email: [email protected]

Venoms to drugs: translating toxins into therapeutics We are interested in the evolution, structure, pharmacology, and potential therapeutic applications of disulfide-stabilised peptides from the venoms of centipedes and spiders. Our primary focus is the discovery, structure-function characterisation, and therapeutic development of venom peptides that modulate the activity of neuronal ion channels involved in pain signalling in humans. Molecules that antagonise these ion channels have the potential to be developed as analgesics. We are currently focussed on developing selective, high-affinity blockers of three human ion channels—acid sensing ion channel (ASIC) 1a and 3, and the voltage-gated sodium channel 1.7 (NaV1.7). Selective blockers of the latter channel are likely to have broad utility against a wide range of pain types since humans with loss-of-function mutations in NaV1.7 have a congenital inability to sense any kind of pain without deleterious affects on any other sensory modalities except olfaction. We have a collection of >300 arthropod venoms that can be used in high-throughput screens against ion channels of interest. Using this approach, we showed that spider venoms are the best natural source of NaV1.7 modulators with 35% of all venoms screened containing at least one blocker of this channel. We have already purified 40 spider-venom peptides that block this highly sought after analgesic target. One lead molecule has already progressed to preclinical studies in rodent pain models. We recently discovered the most potent known blocker of human ASIC1a, which inhibits the channel with an IC50 of 500 pM. This venom peptide has potential not only as an analgesic but also as a therapeutic designed to ameliorate the neuronal injury often associated with ischemic stroke. Current projects include: 1. Development of novel analgesic drugs based on spider-venom peptides 2. Development of novel anti-stroke therapeutics based on spider-venom peptides 3. Molecular evolution of spider and centipede venoms Background reading 1. King GF (2011) Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin. Biol. Ther. 11, 1469–1484. 2. Vetter I, Davis JL, Rash LD, Anangi R, Mobli M, Alewood PF, Lewis RJ and King GF (2011) Venomics: a new paradigm for natural-products-based drug discovery. Amino Acids 40, 15–28. 3. Escoubas P & King GF (2009) Venomics as a drug discovery platform. Expert Rev. Proteomics 6, 221–224.



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PROFESSOR BOSTJAN KOBE


Structural Biology of Infection, Immunity and Molecular Recognition The recognition of proteins by other proteins and ligands occurs in essentially every cellular process. We are trying to understand this process at the structural level, focusing particularly on the processes of infection and immunity. Our group is using an integrated approach combining determination of three-dimensional structures (with major emphasis on X-ray crystallography) with computational techniques, methods for quantitative evaluation of interactions such as the biosensor, protein chemistry and molecular biology. Project 1: Structural studies of proteins involved in innate immunity in mammals and plants The aim of this project is to use structural biology to understand the molecular basis of processes involved in the innate immune response in mammals and plants, with implications for infectious and inflammatory disease, cancer and agriculture. The projects involve protein expression, purification, crystallization and structure determination. Project 2: Structural studies of proteins involved in bacterial pathogenesis The aim of this project is to use structural biology to understand the processes of bacterial pathogenesis by different bacterial pathogens. The projects involve protein expression, purification, crystallization and structure determination. Project 3: Understanding the mechanism and specificity of nucleo-cytoplasmic transport The aim of this project is to understand the mechanism of transport of proteins into the nucleus, including the specificity and regulation, with the long-term goal of manipulating this essential process. The projects involve protein expression, purification, crystallization and structure determination, as well as bioinformatics aspects. Project 4: Linear motifs in signal transduction Linear sequence motifs are recognized in many signalling processes, including protein kinases and phospho-peptide binding domains. The project currently has a computational focus on developing bioinformatic tools that integrates structural information with sequence and other available data.



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DR SHIH-CHUN LO (LAWRENCE) Centre for Organic Photonics & Electronics School of Chemistry & Molecular Biosciences Phone: 07 3346 7657 Email: [email protected]

Organic materials and Nanotechnology We are focusing on developing new classes of nanomaterials mainly for energy related applications, such as photon-induced water splitting (for H2 generation), solar cells, and organic light emitting diode (OLEDs) as well as bio-applications. Honours students will learn how to design, synthesise and characterise these frontier functional materials. Project 1: Clean hydrogen fuel generation

The use of hydrogen gas as a renewable and clean fuel has been one of the most exciting research fields, in particular, direct hydrogen creation from water driven by sunlight. Developing efficient and long-lasting water-splitting photosensitisers and catalysts has been the key challenge for the technology. The project is to synthesise and characterise new water-splitting photosensitizers for effective light absorption and catalysts for efficient water decomposition.

Project 2: Advanced materials for opto-electronics (e.g., OLEDs, solar cells, and photodiodes)

The project is to develop new electro-active materials for OLEDs, solar cells, and photodiodes for our next generation flat-panel displays (e.g., mobile phones, tablets, monitor displays and TVs for the superior display-quality and superb energy saving), renewable energy generation and high-sensitive detectors. The project will involve organic/organometallic and physical chemistry, and students will learn how to fabricate and

characterise these devices by closely working with device physicists. Project 3: Biomaterials for imaging and treatment Photodynamic therapy (PDT) has been developed to provide non-invasive (compared with conventional surgery) and less side effects (compared to chemotherapy) for cancer treatment. PDT can be accurately targeted, and repeatedly administered without the total-dose limitations related with radiotherapy and result in little or no scarring after healing. To facilitate the advantages of PDT, we are developing novel bio-compatible photodynamic therapy agents for deeper tissue treatment with less photodamage with effective two-photon absorption activities.



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DR PATRICIA LOPEZ-SANCHEZ

Centre for Nutrition and Food Sciences ARC Centre of Excellence in Plant Cell Walls Phone: 07 3346 7373 Email: [email protected]

Our research focuses on the relationship between the chemical composition-architecture and material properties of cell walls in plants. The physical properties of the cell wall have direct implications for the use of plant material in many technological fields such biomaterials for medical applications, agri-food industry, paper production and environmentally friendly energy sources. Furthermore material properties are relevant for many plant bioprocesses, for example the wall has to be rigid to withstand external and internal forces and at the same time flexible enough to allow for growth and development of the plant. These features make the plant cell wall an outstanding material. Project 1: Structure-function of engineered cell walls: a way to broaden the biotechnological applications of plant materials This project will make use of model plant systems such as bacterium Gluconacetobacter xylinus which produces pure cellulose in liquid fermentation. By using microbiological techniques and including chosen cell wall polymers in the fermentation medium, a range of cellulose-based composites can be engineered which have many properties remarkably similar to plant cell walls. Their materials properties will be characterized using stress controlled rheometers, before and after being subjected to mechanical forces (MPa) characteristic of the turgor pressure found in growing plants. With this approach, we aim to obtain a first understanding of the molecular basis for plant cell wall properties under active turgor pressure. The implications of such studies will contribute to the use of plant-based materials for food, pharmaceutical and medical applications. Project 2: Mimicking nature by using polysaccharides as building blocks for cereal endosperms walls Cereals are one of the main components of the human diet worldwide. In their natural form, they are a rich source of vitamins, minerals, carbohydrates (fibre), fats and protein. However, when refined the remaining endosperm (‘white flour’) is mostly carbohydrates, such as starch enclosed by cell walls containing β-glucan and arabinoxylan. Extraction of cell wall components disrupts the architecture of the wall, which is key in determining its material properties. Therefore the development of models to mimic cell wall architecture is highly relevant to study the underlying relationships between their composition, microstructure and material properties. In order to build these cell wall analogues we will make use of enzymatic treatments and cryogelation of polysaccharides, a method which uses freeze-thawing cycles to form physically cross-linked networks .The outcomes of the project will contribute to advancing scientific understanding of plant cell wall biology to enable sustainable biomass production for food security and human health.



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PROFESSOR ALAN E. MARK

Molecular Dynamics School of Chemistry & Molecular Biosciences Phone: 07 3365 4180 Email: [email protected] Websites: http://profiles.bacs.uq.edu.au/Alan.Mark.html http://compbio.chemistry.uq.edu.au/md/

The group uses computer simulation techniques to model the dynamic behaviour of biomolecular systems such as proteins, nucleic acids and lipid aggregates. The simulation software and atomic force fields we develop are used to understand processes such as how peptides fold and self-assemble into functional complexes or how anti-microbial peptides enter cells. We look for students interested in working at the interface between structural biology, chemistry, and computational science. Possible projects include: Project 1: The nucleation and growth of amyloid fibrils Amyloid fibrils are self-assembled peptide aggregates associated with a range of neurodegenerative diseases. Molecular dynamics (MD) simulation techniques will be used to shed light on the structure and formation of amyloid fibrils. In particular, simulations will be used to identify the minimal stable structure required for fibril growth. Project 2: The activation of the growth hormone receptor The activation of cell surface receptors is a critical step in cell regulation. MD simulations will be used to characterize the conformational changes that accompany the binding of growth hormone to its receptor thereby shedding light on the mechanism of action of cytokine receptors in general. Project 3: Predicting protein-ligand interactions Free energy calculations are a highly accurate but computationally expensive method for predicting binding affinities. You will help refine and test a computationally efficient single-point free energy methodology developed within the group for use in virtual drug screening.

Project 4: Membrane protein assembly (anti-microbial peptides and viral fusion proteins) Despite their importance, little is known about to how membrane peptides and proteins assemble into functional complexes. To investigate this we are studying a range of small anti-microbial peptides that spontaneously self-assemble within membranes inducing pore formation, membrane fusion, or even cell death. On a larger scale we are studying how proteins of enveloped viruses such as Dengue and Ebola drive the fusion of the viral and cell membranes. This is a key step in the entry of the virus into cells and a prime target for therapeutic intervention.

The peptide Magianin interacting with a DPPC bilayer showing the formation of a transmembrane pore.


http://profiles.bacs.uq.edu.au/Alan.Mark.html

http://compbio.chemistry.uq.edu.au/md/


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PROFESSOR DANIEL MARKOVICH

Ion Transport and Cell Signalling Molecular Biology and Biotechnology School of Biomedical Sciences Phone: 07 3365 1400 Email: [email protected] Website: http://www.uq.edu.au/sbms/staff/professor-daniel-markovich

Membrane Transporters: Biochemistry, Molecular Biology and Physiology Prof Daniel Markovich’s interests lie in the study of the biochemistry, (patho)physiology and genomics of mammalian ion transporters, involved in transcellular movement of ions (sulfate, chloride, oxalate) across epithelial cells. In the last few years, several membrane transporters have been cloned, characterised and knock-out mice generated in his laboratory. The following Honours/MPhil/PhD projects are currently available in his laboratory: • Project 1: Biochemical roles of polymorphisms in human sulfate transporters • Project 2: Trafficking of human sulfate transporters in mammalian cells • Project 3: Second messenger pathways regulation of human sulfate transporters Using modern molecular and cellular biological techniques, these projects study the molecular function and regulation of ion transport systems by characterising their protein and mRNA expression in both in vitro (in established cell lines) and in vivo (animal models, Xenopus laevis oocytes) systems. These studies will elucidate the function and molecular regulation of these transporters in the body, which will help in clarifying their roles in ion homeostasis, which will provide important insights into diseases associated with membrane transport processes. Selected Publications Markovich D (2012) Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters. Physiology 27: 7-14 Markovich D (2011) Physiological roles of renal anion transporters Nas1 and Sat1. Am. J. Physiol.-Renal. Physiol. 300: F1267-70 Dawson PA, Russell CS, Lee S, McLeay SC, van Dongen JM, Cowley DM, Clarke LA, Markovich D (2010) Hepatotoxicity and urolithiasis in Sat1 transporter (Slc26a1) null mice. J. Clin. Invest. 120: 706-12 Markovich D and Aronson PS (2007) Specificity and regulation of renal sulfate transporters. Ann. Rev. Physiol. 69:7.1-7.15 Dawson PA and Markovich D (2005) Pathogenetics of the human SLC26 transporters. Curr. Med. Chem. 12: 385-396 Dawson PA, Beck L and Markovich D (2003). Hyposulfatemia, growth retardation, reduced fertility and seizures in mice lacking a functional NaSi-1 gene. Proc.Natl.Acad.Sci.USA 100 (23):13704-9


http://www.uq.edu.au/sbms/staff/professor-daniel-markovich


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ASSOCIATE PROFESSOR FRED MEUNIER

Molecular Dynamics of Synaptic Function Lab Queensland Brain Institute / School of Biomedical Sciences Phone: 07 3346 6373 Email: [email protected]

The focus of our laboratory is to decipher the dynamics of molecular events taking place during nerve cells communication and plasticity. Our ultimate aim is to understand the sequence of interactions underlying neurotransmitter release and neuronal sprouting and to utilise this knowledge to design therapeutic strategies for treating human diseases affecting the nervous system such as neurodegenerative diseases. Examples of available projects are:

Project 1: Biotechnology to help treat motoneuronal diseases Motoneuronal diseases are notoriously difficult to treat and one of the main hindrances to treatment is the relative inaccessibility of motoneurons. We are designing probes to deliver fluorescently-labelled molecules specifically in motoneurons.

Project 2: Biotechnology to image dynamic events in living neurons Design novel methods to investigate the neurons’ internal trafficking of vesicles involved in nerve cell communication. This project will aim designing new optical tools and methods for investigating vesicle trafficking in living neurons.



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ASSOCIATE PROFESSOR CHAMINDIE PUNYADEERA School of Biomedical Sciences /Institute of Health and Biomedical Innovations Queensland University of Technology Phone: 07 3138 0830 Email: [email protected]

Project 1: Early Cancer Detection using a Saliva Sample

Background: Cancer is the leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008 (WHO, 2011 February Report). Tobacco use is a major risk factor for head and neck cancer and lung cancers, and smoking kills over 1,000,000 people a year, causing 30% of all cancer-related deaths in the western societies. The direct impact of smoking can clearly be seen in the oral cavity due to its proximity, thus, human saliva is an ideal diagnostic medium for investigating smoking-related cancers. DNA methylation in cells is one of the earliest events that occur during cancer initiation and has demonstrated considerable utility by enabling early disease detection, better disease stratification, and predicting disease relapse and response to therapy in cancer and other diseases (Esteller, M. Epigenetics in Cancer, New England Journal of Medicine, 358: 2008). We are developing cutting-edge tools to diagnose cancer at an early stage, Changing Traditional Health Care Paradigm. Project aims: Identify and validate biomarkers in saliva for early detection and staging of head and neck cancers.

Benefits for you?

• You will have access to the state of the art facilities and will gain experience in working in a multidisciplinary team, focused on cutting-edge science

• You will develop laboratory skills in molecular biology, cell cultures and biochemistry • You will have an opportunity also work in hospitals

Project 2: Saving Hearts with a Simple Saliva Test

Background: Cardiovascular diseases (CVD) including heart, stroke and blood vessel disease, affect about 3.67 million Australians. Every 10 minutes ONE Australian dies from CVD. An increase in CVD in Australia is accelerated by growing as well as an aging population. Human saliva as a diagnostic medium has gained attention in the last decade due to its non-invasiveness, easy sampling and lower threat of transmitting infection. Human saliva is the window to our body and saliva mirrors biomarkers found in blood. Up until now, there have been ~ 2000 proteins found in human saliva and about ~26% are also present in blood, highlighting the importance of saliva for clinical research. Project aims: To develop non-invasive low cost tools to detect heart disease at an early stage. The Saliva Translational Research Team: Our team is young, dynamic and vibrant, and is multidisciplinary. We are geared at investigating the diagnostic potential of human saliva aimed at translating our research findings into a clinical setting. Collaborators: Professor Ian Frazer

Professor John Atherton Professor Henry Krum (Monash University). Professor James Herman (John Hopkins University, Baltimore, USA) Professor Karam Kostner Professor William B Coman



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DR STEVEN REID

Deputy Director, Biotechnology Program School of Chemistry & Molecular Biosciences Phone: 07 3365 3991 Email: [email protected]

Research Area: Production of Baculovirus Biopesticides – A Systems Biology Approach Increased resistance to chemical pesticides and concern over their use has renewed interest in the application of biological means to control pests of commercial importance. Many wild type Baculoviruses can specifically infect and kill key agricultural caterpillar pests and some virus strains can also target mosquitoes. The Reid laboratory has a process patent on a procedure for producing Baculoviruses via fermentation. The lead product is a Baculovirus targeting the Helicoverpa pest species, which is responsible for a current $US3.2 billion per annum market in traditional chemicals. A baculovirus product manufactured by the Reid Group and formulated by Bioflexus has been registered for use on Australian crops to combat heliothis caterpillars (more widely known as the cotton bollworm), under the trade name of ‘Heliocide’. The Reid Group is undertaking further research to increase current yields, to enable manufacture and evaluation in the niche Australian market. Currently the Group is collaborating with Professor Lars Nielsen to use a Systems Biology approach utilising transciptomic and metabolomic techniques in an effort to understand how the virus interacts with host cells in culture. The team anticipates further increases in yield, making it cost effective in broader markets, both national and international. Specific Research projects: Project 1: Development of a Heliothis BACMID system for manipulation of the H.arm virus genome

(gene knockouts). This system will be used to generate altered viruses for further transciptomic and metabolomic studies.

Project 2: The use of Real Time PCR to quantify virus binding kinetics to enable optimisation of early

process steps for the manufacture of virus in vitro Project 3: Development of sample extraction procedures and appropriate HPLC/GC-MS techniques

for quantifying intracellular metabolite levels for infected and non infected cells in culture. These procedures are essential to enable our metabolomic studies.



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ASSOCIATE PROFESSOR JOE ROTHNAGEL

School of Chemistry & Molecular Biosciences Phone: 07 3365 4629 Email: [email protected] Website: http://www.scmb.uq.edu.au/staff/index.html?page=142199

Development of the next generation of gene expression systems A major focus of this laboratory is directed towards the development of new eukaryotic expression vectors. We are investigating the role of post-transcriptional mechanisms in gene expression. This work has led to the development of short cis-acting sequences based on small upstream open reading frames (uORFs) that can be used to modulate gene expression; known as GeneDimmerTM and GeneBooster respectively. Both GeneDimmerTM and GeneBooster expression vectors will ultimately be used in cell biology, gene therapy and agriculture. Experiment procedures and approaches include bioinformatics, gene cloning and analysis, cell culture, transgenic plants, and expression analysis. The development of nucleus - targeting tags for the delivery of gene medicines We have identified a peptide sequence that localises to the nucleolus. We are developing a series of constructs that contain this peptide tag and are evaluating its use in delivering gene medicines to the nucleus. This methodology has the potential to increase the concentration of these genetic constructs in the nucleus thereby increasing their efficacy. We are also developing non-peptide aptamers of this sequence. Biotech Honours Projects will be offered in the following areas: • Development of second generation GeneDimmerTM vectors and their characterisation in eukaryotic cells. • Characterisation of novel small peptides encoded by sORFs (with Ross Smith & Amanda Nouwens)


http://www.scmb.uq.edu.au/staff/index.html?page=142199


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PROFESSOR MARK SCHEMBRI


The common research theme in my laboratory is the study of surface proteins that mediate adhesion, aggregation and biofilm formation by bacterial pathogens. Adhesion is the primary mechanism by which bacteria colonize host tissue surfaces and initiate disease. My research deals primarily with pathogenic Escherichia coli that cause intestinal and extra-intestinal infections. A major focus is uropathogenic E. coli where we study the role of adhesins and other surface components in the development of biofilms and colonisation of the urinary tract. Biofilms are microbial communities characterized by cells that are irreversibly attached to a substratum or interface or to each other. Biofilms are of immense significance in medical, industrial and environmental settings and this area of study has enormous scope and importance in the field of bacterial pathogenesis. My laboratory also investigates mechanisms of adhesion and biofilm formation by other pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter species. Project 1. E. coli is the primary cause of urinary tract infection (UTI) in the developed world. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime. The aim of this project is to study the molecular characteristics of recently emerged multidrug resistant uropathogenic E. coli strains. The project will employ forefront molecular techniques including genome sequence analysis, proteomics, mutagenesis and cloning to characterise multidrug resistant strains and dissect their virulence capacity. Project 2. Autotransporter proteins represent a major group of Gram-negative bacterial secreted proteins that contribute to uropathogenic E. coli mediated UTI. Autotransporter proteins possess a range of virulence properties such as adherence, aggregation, invasion and biofilm formation. We recently characterised a novel translocation and assembly module that promotes efficient secretion of autotransporter proteins across the outer membrane and published this in collaboration with other research groups in Nature Structural & Molecular Biology. Recent genome sequencing of several uropathogenic E. coli strains has also identified a number of previously uncharacterised autotransporter proteins and we are currently trying to understand their contribution to virulence. This study aims to characterise some of these genes and their products, study their mode of translocation across the outer membrane and evaluate their role in adhesion, colonization and biofilm formation. Project 3. Colonization of the bladder by uropathogenic E. coli results in the formation of intracellular cell aggregates encased in a polysaccharide-rich matrix (i.e. a biofilm). These structures enable the bacteria to cause chronic, persistent infections. Biofilm formation on medical implants such as catheters is also a major source of recurrent infection and resistance to antibiotics. This project will examine the role of several putative virulence factors (including uncharacterised fimbrial adhesins) from uropathogenic E. coli that are associated with biofilm formation. Project 4. Klebsiella are frequent causes of nosocomial infections; it is estimated that they account for 8% of all hospital acquired infections in the western world. Next to E. coli infection, Klebsiella is the most common cause of Gram-negative septicemia with a fatality rate of 25-50%. In the majority of bacteremic cases, the focus of infection is the urinary tract. This project will identify and characterize novel virulence factors from Klebsiella pneumoniae.



60

DR HORST JOACHIM SCHIRRA

Centre for Advanced Imaging Phone: 07 3346 0360 Email: [email protected]

NMR-based metabonomics in clinical applications and environmental science (3 projects) We try to solve the puzzle of metabolic pathways with NMR metabonomics. NMR metabonomics is the newest frontier technology in systems biology. It analyses biological or clinical samples, such as cell extracts, urine, and blood, by looking at the global composition of body fluids. We want to identify systematic patterns or metabolic fingerprints that are associated with diseases, specific physiological states, environmental or genetic conditions. Diseases and related conditions, as well as environmental or genetic changes lead to global metabolic changes that are reflected in the composition of biofluids and can thus be identified. These changes can then be used as diagnostic markers for identifying individuals at risk, for identifying successful intervention strategies, and for following and monitoring treatment in patients. The technique is powerful, as it can identify trends and metabolic changes that could be missed by a narrow approach of screening only select metabolites or metabolite classes. We study metabolic changes by investigating the chemical composition of biofluids with NMR spectroscopy. Changes in the metabolic profile of e.g. urine are studied by multivariate statistical analysis and let us pinpoint, which parts of the organism’s metabolism are disturbed. Thus, by understanding how disease affects the metabolism of an individual and by understanding the metabolic consequences of a disease we might learn something about the mechanism of a particular disease itself. I have several projects available in this area, focussing on a variety of model diseases. Current projects involve the study of the effects of growth hormone receptor mutations in mice, the mechanism of phosphine resistance in C. elegans, as well as several projects aimed at developing NMR metabonomics as a tool for clinical diagnosis. Some of our animal model systems are very well understood, and in these cases we are trying to take the next step by investigating the connection between genotype and phenotype on a systematic level. The practical use of NMR metabonomics involves the analysis of a multitude of NMR spectra and correlation of these data with other data from physiology, biochemistry, or clinical assessments. This multimodal analysis is at the cutting edge of systems biology and requires the development of novel analytical tools and techniques. Thus, students with an interest or background in mutivariate statistics, programming and/or bioinformatics are highly welcome in this environment, apart from students with experience in chemistry and/or biochemistry. Individual Projects: Three main projects in NMR-based metabonomics are available in 2010: One project centres on the early detection of Prostate Cancer and will be conducted in collaboration with Prof Frank Gardiner (UQ Centre for Clinical Research/Royal Brisbane and Women’s Hospital). The second project focuses on oral diseases and their contribution to the total inflammatory burden of a patient, and will be conducted in collaboration with Dr Pauline Ford (School of Oral Biology/Prince Charles Hospital). The third project aims to close the gap between genotype and phenotype by characterising a cohort of mice with mutations in the growth hormone receptor that leads to late-onset obesity. This project is in collaboration with Prof Mike Waters (IMB) and Prof Lars Nielsen (AIBN). All projects will be conducted in SCMB using the extensive NMR infrastructure of the Centre for Magnetic Resonance and the Institute for Molecular Bioscience. The potential for follow-on PhD projects exists, depending on successful APD scholarships.



61

DR BENJAMIN SCHULZ


Molecular Systems Glycobiology My research focuses on the mechanisms, biological roles and applications in biotechnology of glycosylation, the most abundant and complex post-translational modification of proteins. Glycosylation is important in biological processes such as human development, cancer and microbial infection. This is because glycosylation is essential in biological activities as diverse as protein folding, fine-tuning protein enzymatic activity and determining protein-protein interactions. Half of all proteins are glycosylated, and a single protein can be modified by hundreds of different sugar moieties. The diversity of glycoproteins therefore requires that we take a systems biology approach in our research. We aim to understand the mechanisms controlling glycosylation in these various systems to develop diagnostics, therapies, vaccines and applications in biotechnology. Project 1. Engineering glycoproteins for improved expression Many proteins currently used as pharmaceuticals or in biotechnology are glycoproteins, such as erythropoietin (EPO) and monoclonal antibodies. These glycoproteins are generally made using expensive mammalian cell expression systems. We have developed and filed a patent for a technology that involves minimal modification of the amino acid sequence of a glycoprotein, which then allows the protein to be expressed in low-cost bacterial expression systems. This project will further develop this technology using site-directed mutagenesis, protein expression, purification and characterization. Project 2: Drug resistance and N-glycosylation in breast cancer Docetaxel is an important chemotherapeutic drug for treatment of breast cancer. However, it is very common that tumours develop resistance to docetaxel. Recent studies have shown that the cellular pathway of protein glycosylation is important in the development of docetaxel resistance. This study seeks to understand how these cellular changes allow tumours to become resistant to docetaxel. This project will use cell culture, mass spectrometry proteomics and bioinformatics. Project 3: Bacterial glycoengineering It was recently reported that some bacterial pathogens, including Haemophilus influenzae, encode systems for cytoplasmic protein N-glycosylation. This project will use in vitro protein biochemistry and a non-pathogenic E. coli in vivo system to investigate the mechanisms of this process and its potential applications in biotechnology.



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ASSOCIATE PROFESSOR CONRAD SERNIA

School of Biomedical Sciences Phone: 07 3365 3180 Email: [email protected]

Endocrinology of Angiotensin Angiotensin is a small peptide hormone that is commonly associated with blood pressure and salt balance. Two widely prescribed classes of antihypertensive drugs are based on interference with Angiotensin action: the angiotensin receptor antagonists (eg. Losartan) and angiotensin-converting enzyme inhibitors (eg. Captopril). This lab is interested in uncovering links between angiotensin and degenerative diseases that may be consequential to, or independent of, cardiovascular effects. The current focus is on Alzheimer’s Disease, Oxidative Stress and Osteoporosis. Project 1: Alzheimer’s Disease: angiotensin regulation of amyloid precursor protein (APP) in neurones Project 2: Osteoporosis: angiotensin action on osteoblasts with particular emphasis on RANKL/OPG regulation. Project 3: Involvement of angiotensin-mediated oxidative stress in (1) and (2) above. Collaboration: The laboratory collaborates with Prof Lindsay Brown (USQ); Prof Wally Thomas (UQ) and Prof Po Leung (Chinese University of Hong Kong). Research Techniques: General endocrine methods, cell culture, molecular techniques. Selected Publications: SERNIA C. A critical appraisal of the intrinsic pancreatic angiotensin-generating system. J Pancreas 2:50- 55. 2001 Leung PS SERNIA C. The renin-angiotensin system and male reproduction: new functions for old hormones. Molec Cell Endocrin 30: 263-70, 2003 Sernia, C., Tang, Z., Kerr, D., & Wyse, B. (1997) Novel perspectives on pituitary and brain angiotensinogen. Front. Neuroendocrin. 18(2): 174-208. Wyse, B. & Sernia, C. (1997) Growth hormone regulates AT1a angiotensin receptors in astrocytes. Endocrinol. 138: 4176-4180. Greenland K SERNIA C. Oestrogenic regulation of brain angiotensinogen. J Neuroendocrin 16: 508-515, 2004. SERNIA C Huang H et al. (2007). Bone Homeostasis: an emerging role for the renin-angiotensin system. In “Proteases of the rennin-angiotensin system in Human Disease” ed. P.Leung, Springer Verlag, pp263-287.



63

DR YASMINA SULTANBAWA

Queensland Alliance for Agriculture and Food Innovation (QAAFI) Phone: 07 3276 6037 Email: [email protected] [email protected]

Project 1: Antimicrobial efficacy of Leptospermum polygalyfolium honey with different levels of methylglyoxal contents against MRSA and Pseudomonas Recent studies on Leptospermum polygalifolium a myrtle native to Australia has shown antibacterial activity against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Escherichia coli (Sultanbawa and Smyth 2010). The most extensively studied leptospermum species is Leptospermum scoparium ((Cooper, Molan et al. 1999; Henriques, Jenkins et al. 2010)) and this is the source of the well known bioactive honey manuka from New Zealand. The honey from Leptospermum polygalifolium which is harvested by the bees from a monofloral source and is only found in Australia could be branded and marketed in a similar manner to the manuka honey. However, scientific evidence for the use of the Australian honey for wound infections is limited and more studies are needed to prove efficacy. Methylglyoxal (MGO) one of the phytochemicals present in this honey has been identified as one of the chemical components responsible for antimicrobial activity ((Adams, Boult et al. 2008; Mavric, Wittmann et al. 2008; Adams, Manley-Harris et al. 2009)). MGO levels of 1.1 – 1.8 mM in Leptospermum scoparium has indicated antibacterial activity ((Mavric, Wittmann et al. 2008)). Our studies indicate higher levels of MGO in honeys from Leptospermum polygalifolium. The aim of this project is to understand the mechanisms that govern the antimicrobial activity of this honey at different levels of MGO ranging from 300 – 1750 mg/kg against MRSA and Pseudomonas aeruginosa. Project 2: Determining the inhibitory effects of Leptospermum polygalyfolium honey on biofilms of MRSA and Pseudomonas. Honey is well known for its wound healing properties and one of the contributing factors is the antibacterial activity in honey. With the increase use of antibiotics in medicine there has been a rise in prevalence of antibiotic resistance bacteria such as MRSA. As a result there has been an urgent need to find alternative antimicrobial strategies which include bioprospecting for natural sources and also changing the methods used to elucidate antimicrobial activity. Honey as a natural antimicrobial is important as it has a potent in vitro activity against antibiotic resistant bacteria and it has been successfully used in the treatment of chronic wound infections not responding to antibiotic treatment. Information on the antimicrobial activity of the Australian honey Leptospermum polygalifolium and mechanisms that are responsible for inhibiting quorum sensing signals which in turn affect the growth of biofilms will contribute to scientific evidence for the use of honey as a conventional and natural treatment. The aim of this study is to understand the inhibiting effects of Leptospermum polygalifolium in the formation of biofilms from MRSA and Pseudomonas.




64

DR KATE STACEY


Recognition of Cytosolic DNA as a Danger Signal The DNA of eukaryotic cells is contained within a membrane-bound nucleus, and the appearance of DNA within the cytosol indicates a danger to the cell. Cytosolic DNA can result from viral and bacterial infections or the activity of endogenous retroviruses within the human genome. Responses to cytosolic DNA include production of the anti-viral protein interferon-beta, and cell death. We identified AIM2 as a receptor for cytoplasmic DNA eliciting cell death. AIM2 initiates formation of an “inflammasome” which is a protein complex leading to activation of the protease caspase-1 and lytic cell death. We have recently shown that AIM2 recognition of DNA also recruits and activates caspase-8, which leads to the death of cells by apoptosis. Although the AIM2 pathway is only found in mammals, we find that chicken and insect cells can also die after introduction of DNA into the cytosol. Consequently we propose that defences against invading DNA are essential for defending against infections and guarding the genome of all multicellular organisms. Future studies will focus on:- 1) Characterisation of the role of DNA detection in combatting viral infections 2) Definition of pathways of recognition of foreign DNA in non-mammals 3) Characterisation of the inflammasome complex induced by AIM2, and novel death-domain interactions involved in recruitment of procaspase-8 4) Investigation of the role of AIM2 (absent in melanoma 2) as a tumour suppressor Inflammasome Deficiency in Autoimmune Disease The human autoimmune disease lupus involves formation of antibodies against self molecules and their deposition as immune complexes in tissues. Inflammasomes lead not only to cell death but also to release of the inflammatory cytokine IL-1b. Although most researchers have assumed that inflammasome pathways will be elevated in autoimmunity, we find the opposite; in a mouse model of lupus there is profound deficiency of three different types of inflammasome structures. We propose this leads to an altered response to commensal organisms and poor clearance of pathogens, and promotes autoimmunity. Projects will include: 1) Establishing the molecular basis for inflammasome deficiency in the mouse 2) Investigating whether human lupus patients have inflammasome deficiency Relevant Publication: Roberts, T.L., Idris, A., Dunn, J.A., Kelly, G.M., Burnton, C.M., Hodgson, S., Hardy, L.L., Garceau, V., Sweet, M.J., Ross, I.L., Hume, D.A., Stacey, K.J. (2009) HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323:1057-1060.



65

DR MATT SWEET


Project 1: Targeting Histone Deacetylases in Inflammation Acetylation of lysine side chains on proteins regulates diverse cellular processes including signalling, transcription and protein targeting. Histone deacetylases (HDACs) are a family of enzymes that deacetylate lysine side-chains, and inhibitors of these enzymes have efficacy as anti-cancer agents. HDAC inhibitors also display anti-inflammatory properties. This project will investigate the role of specific HDACs in regulating inflammatory responses of macrophages. Project 2: Characterizing Human-specific Inflammatory pathways Mice are routinely used in immunological models to study disease processes. Specific immune responses are not necessarily conserved between mice and humans however, because the innate immune system is under strong evolutionary pressure. Using expression profiling, we have identified innate immune genes that have conserved regulation between mice and humans, as well as those that are divergent. This project will explore the function of innate immune genes that display human-specific regulation.



66

PROFESSOR STEPHEN TAYLOR

School of Biomedical Sciences Phone: 07 3365 3124 Email: [email protected]

Drug Discovery and Development A major problem in clinical medicine is the effective treatment of many cruel diseases. Many of the worst human ailments concern disorders of the immune and inflammatory systems, where the body seemingly attacks its own tissues. The treatments for these kinds of disorders are limited, or toxic, or just plain ineffective. Some of these diseases can kill in just a few days, some may slowly kill or disable over years or even decades. The human suffering is incalculable and progress seems negligible. In Dr Taylor’s laboratory, new classes of anti-inflammatory drugs are being developed, in collaboration with chemists at the IMB (Professor David Fairlie’s group). We have successfully discovered and developed orally active complement C5a antagonists and phospholipase A2 inhibitors. The C5a antagonist project has led to the formation of the spin-off company, Promics Pty Ltd, and the filing of several key patents. Projects are available for students to work on the preclinical pharmacology of lead compounds or with new analogues. The work entails cellular, biochemical and whole animal studies, and is aimed at determining the pharmacological activity of these new agents.



67

DR HANG TA NHMRC Early Career Fellow (Whittaker Group) Australian Institute for Bioengineering & Nanotechnology Phone: +61 7 33463851 Email: [email protected]

Novel approaches in diagnosis and treatment of cardiovascular disease Did you know that cardiovascular disease is Australia’s greatest health problem. It kills more people than any other disease and creates enormous costs for the health care system. It places a heavy burden on individuals and the community due to resulting disabilities. Atherosclerosis is the major cause of ischemic heart disease which is the most common form of cardiovascular disease and the leading cause of sudden death, accounting for 34% of all death in Australia in 2008. Despite primary and secondary prevention, thrombotic and embolic events such as myocardial infarction and stroke remain a major health issue and are leading causes of mortality and morbidity in Australia and worldwide. Currently, the detection of these diseases is limited due to the lack of sensitive imaging methods and it usually involves invasive procedures. Our group is working on different approaches to improve diagnosis and treatment of these diseases. We are located within Australian Institute for Bioengineering and Nanotechnology (AIBN) and has access to state-of-the-art facilities in bioengineering/biotechnology and nanotechnology. AIBN offers a dynamic research environment and is home to world-class researchers working at the interface of the biological, chemical and physical sciences. Current projects available include: 1. Smart magnetic resonance imaging nano-sensor for detecting and grading diseases The early detection and accurate characterization of life-threatening diseases such as cardiovascular disease and cancer are critical to the design of treatment. This project will develop smart magnetic resonance imaging nano-sensors that can not only detect, but also sense and report the stage or progression of cardiovascular diseases such as thrombosis, the leading cause of death in Australia and worldwide. 2. Bifunctionalised nano-agents for simultaneous diagnosis and treatment of cardiovascular diseases Cardiovascular disease is the major cause of mortality and morbidity in developed countries. It kills one Australian every 12 minutes. Unstable vulnerable atherosclerotic plaques can rupture and cause thrombosis, resulting in acute coronary syndromes, myocardial infarction and stroke. This project aims to develop targeted smart nano-agents that can image vulnerable plaques and thrombosis; and simultaneously provide anti-thrombotic activity. 3. Anti-inflammatory imaging nanomaterials for theranostics of diseases Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Chronic inflammation might lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. This project will investigate novel approaches to develop nanomaterials which combine both therapeutic and diagnostic capabilities for inflammatory diseases in one dose.

https://exchange.uq.edu.au/owa/redir.aspx?C=5baec34c30cc4de1bfea24bad0843bd2&URL=mailto%3az.gu%40uq.edu.au

http://en.wikipedia.org/wiki/Pathogen

http://en.wikipedia.org/wiki/Hay_fever

http://en.wikipedia.org/wiki/Hay_fever

http://en.wikipedia.org/wiki/Periodontitis

http://en.wikipedia.org/wiki/Atherosclerosis

http://en.wikipedia.org/wiki/Rheumatoid_arthritis


68

DR SIMON WORRALL


Mechanisms of Drug-Induced Tissue Injury Liver, muscle, heart and brain injury have long been associated with the abuse and clinical use of drugs. My research interests focus on ethanol, perhaps the most commonly abused drug. Ethanol is widely tolerated but induces tissue injury in a small number of individuals. The potential research projects listed below will investigate immunological and genetic phenomena associated with alcohol-induced tissue injury. The potential projects available are: 1. Studies on the aetiology of ethanol- induced tissue injury to liver, skeletal and cardiac muscle, and brain? 2. Is protein modification by ethanol metabolites involved in the aetiology of: a. Alcoholic liver disease? b. Alcoholic skeletal and cardiac myopathy? c. Alcoholic brain injury (with Peter Dodd)? 3. Novel protein modifications induced by ethanol metabolism (with Craig Williams, chemistry) 4. Discovery of molecular markers for the severity of Alzheimer’s disease.

(Top):A reaction scheme showing the formation of malondialdehyde-acetaldehyde adducts. (Left):Expression of GFP-tagged human keratin 18 in a primary rat hepatocyte.



69

PROFESSOR PAUL YOUNG

Head of School Virology Unit School of Chemistry & Molecular Biosciences Phone: 07 3365 4646 Email: [email protected]

Dr Young’s group is focused on the molecular biology and immunopathology of viral infections. The primary goals of this research are to gain a clearer understanding of the pathogenesis of severe disease as well as the development of novel vaccine and anti-viral strategies for the control of infections and improved molecular diagnosis. Our laboratory has expertise in the areas of molecular biology, cell biology, structural biology, protein biochemistry and immunology. Additional projects are likely to be available on discussion. Project 1-Development of a dengue virus DNA vaccine based on a novel chimeric form of an immunogenic viral protein. We have been investigating sub-unit and DNA based vaccine strategies for the dengue viruses for some years. Many of these have been based on expression of the immunogenic NS1 protein and we have successfully demonstrated sold protection against viral challenge using a prime-boost approach using a combination of DNA and recombinant sub-unit protein. We wish to expand our array of immunogenic species through the inclusion of a novel chimeric construct that would provide protection against all four serotypes of dengue virus. The project will involve the PCR amplification, cloning and expression as a single fusion protein of domains from all four dengue virus serotypes. Both E.coli and recombinant baculovirus expression will be examined. If time permits, the expressed product will be trialled in a vaccine/challenge study. Project 2-Development of a novel epitope tagging system for purification of recombinant fusion proteins. This project would suit a student interested in biotechnology applications of molecular biology. We have identified the linear amino acid sequences recognized by a series of high affinity monoclonal antibodies. We want to test whether the fusion of these short peptide epitopes to foreign proteins can aid in their purification via immuno-affinity chromatography – a well established tool in biotechnology research and development. These epitopes are derived from the dengue virus NS1 protein and the student will be involved initially in generating reporter gene constructs fused to these epitopes in order to examine their suitability as epitope tags. Further studies with defined foreign genes will be examined time permitting. Project 3-Site-directed mutagenesis and recombinant expression of the dengue virus NS1 protein. The NS1 protein of dengue virus is essential for the replication of the virus at the RNA level. It is also secreted from infected cells and is the target of a protective immune response. Paradoxically, it also appears to be directly involved in the pathogenesis of infection. We have 132 been studying the structure and biophysical features of NS1 for some time in order to help elucidate its exact function and these studies are ongoing. This project will fit in with these studies and involve the cloning and expression of sub-domains of NS1 as well as site-directed mutagenesis to identify key residues involved in the cell membrane-association that is thought



70

DR ADRIAN WIEGMANS

Queensland Institute of Medical Research (QIMR) Phone: 07 3362 0339 Email: [email protected]

Deciphering the molecular mechanisms of metastasis to design new-targeted therapies for breast cancer. The transformation of normal breast tissue to tumor requires the accumulation of mutations, which is readily achieved by deregulation of DNA repair pathways. We found that metastatic breast cancers have high levels of the DNA repair protein RAD51. Metastatic breast cancer represents a subtype that has poor clinical outcome and RAD51 contributes to this. We have determined that reducing RAD51 levels in aggressive breast cancers results in reduced metastatic growth and sensitivity to chemotherapy. RAD51 supports metastasis via a role in stabilizing cancer genomes however RAD51 also augments metastatic potential through other mechanisms. These include changes in actin dynamics and changes in gene metastatic expression profiles via mechanisms that have yet to be fully elucidated. We believe that other DNA repair proteins could also harbour these roles. Outcomes from these analyses will provide new potential clinical targets in treating metastatic breast cancer. Individual research projects for developing new therapeutic targets will have a focus around one of the following models; Actin dynamics and metastasis: We find that DNA repair proteins affect actin dynamics, cell morphology and thus the migration and invasion properties of cancer cells. This determines the metastatic potential of the cancer and could be targeted to inhibit metastatic spread of cancer. Transcriptional regulation of metastasis: DNA repair proteins also change the profile of pro-metastatic gene expression via unknown mechanisms. The ability of DNA repair proteins to bind DNA and simultaneously bind transcription factors, mean they have the capability to direct gene expression. This is a new function for this class of proteins. Animal models of metastasis: We are developing new models of metastasis to test new anti-metastatic drugs developed in the lab. We are looking to mimic human diseases, with spontaneous metastasis of breast cancer to specific organs.



71

DR STEFANO FREGUIA Centre for Microbial Electrosynthesis Advanced Water Management Centre Phone: 07 3346 3221 Email: [email protected] My research is at the interface between microbial biotechnology and

electrochemistry, an area known as microbial electrochemistry, which has seen a research boom in the last decade. Electrochemically active bacteria are ubiquitous in nature and are capable of direct and mediated electron transfer to extracellular insoluble electron acceptors, including mineral oxides and positively polarised electrodes. Some of these bacteria are also capable of electron transfer in the opposite direction, i.e. from insoluble electron donors (e.g. metals, elemental sulfur and negatively polarised electrodes) to soluble electron acceptors. These bacteria can be exploited for a number of biotechnological processes, including wastewater treatment with simultaneous electricity production (microbial fuel cells), reductive removal of water pollutants using electricity instead of chemicals, and the concentration of valuable products from wastewater through the use of ion-selective membranes. In particular, these systems can be used to recover precious nutrients from wastewaters. Currently, these nutrients are either discharged in dilute form into the environment or destroyed in energy-intensive wastewater treatment processes. Their recovery and reuse is an important step towards sustainable resource management. We have currently two projects in this area that are suitable for honour or master thesis students. Project 1: Nutrient recovery from source-separated urine using a microbial fuel cell. Urine is an ideal substrate for a microbial fuel cell, as a consequence of its high organic content, high salinity and high buffering capacity. Preliminary results have already shown that the organic compounds present in urine can be effectively oxidised to carbon dioxide at a microbial anode, with concomitant electricity generation. In this project, the aim is to prove the concept of a three-compartment microbial fuel cell to simultaneously achieve (i) complete treatment of urine and (ii) recovery of valuable nutrients (primarily nitrogen, phosphorus and potassium) in the form of a salt. Project 2: Development of a high-rate microbial biocathode for oxygen reduction. For any microbial fuel cell to succeed, a strong cathodic process needs be in place to consume the electrons liberated at the anode. Oxygen is the most suitable electron acceptor in light of its wide availability and high redox potential. The aim of this project is to establish and fully characterise a microbially catalysed oxygen reduction process at a cathode. A number of electrode materials will be tested with mixed microbial cultures supplied only with air and minimal nutrients.



72

PROFESSOR RICHARD LEWIS

Group Leader, Chemistry and Structural Biology Division Director, Centre for Pain Research Phone: 07 3346 2984 Email: [email protected]

Analysis on cone snail venoms using integrated proteomics and transcriptomics to understand the diversity of cone snail venom peptides and how they contribute to the evolution of distinct predatory and defensive venoms.

Identification and characterisation of venom peptides acting at ion channels, GPCRs or transporters with potential to selectively inhibit or activate pain pathways.



73

DR ZYTA ZIORA

Senior Research Officer Institute for Molecular Bioscience Phone: 07 3346 2067 Email: [email protected]

Workshops and other interests: • Writing literature reviews • ITC (isothermal titration microcalorimetry) • Drug design, mode of action, peptide and peptidomimetics chemistry • Thermodynamics of binding between ligands/metal ions and antibiotics

General research outline • Improving antibiotic potency by complexing with metal ions. • Skin treatment for bacterial infection/burns/injury/inflammation/cancer prevention.

Current research projects 1. Enhancement of beta lactams activity through complexation with metal ions. 2. NMR and ITC study of antibiotic complexes with metal ions. 3. Wine tannins, physico-chemical characterization and bio-activity. 4. Bacterial sortase: application to improve antibacterial potency.

My current research projects involve collaboration with: • Project 1 – University of Heidelberg, Germany/UQCCR, UQ. • Project 2 – CAI/IMB. • Project 3 – AWRI, Adelaide/QAAFI. • Project 4 – IMB/ Pharmacy Australia Centre of Excellence.

Selected Recent Publications: Zhou Hang, Matthew A. Cooper, Zyta M. Ziora, Platinum-based anticancer drugs encapsulated liposome and polymeric micelle formulation in clinical trials, Biochemical Compounds, 2016, 4, 1-10.

McRae, J. M.; Ziora Z. M.; Kassara, S.; Cooper, M.A.; Smith, P. A. Ethanol concentration influences the mechanisms of wine tannin interactions with poly(L-proline) in model wine, J. AgricultureFood Chem., 2015, 63, 4345−4352.

Cheng, M.; Ziora, Z. M.; Hansford K.; Blaskovich, M. A.; Butler, M. S.; Cooper, M. A. Anti-cooperative ligand binding and dimerisation in the glycopeptide antibiotic dalbavancin, Org. Biomol. Chem., Org. Biomol. Chem., 2014, 12, 2568.

Ziora, Z. M.; Blaskovich, M. A.; Toth, I.; Cooper, M. A. Lipoamino acids as major components of absorption promoters in drug delivery, Curr. Top. Med. Chem. 2012, 12, 1562-1580.

Ziora, Z. M.; Wimmer, N.; New, R.; Skwarczynski, M.; Toth, I. Lipopeptides for the Fragment-based Pharmaceutics Design, Int. J. Org. Chem. 2012, 2, 75-81. (cover story)

Ziora, Z.; Skwarczynski, M.; Kiso, Y. Medicinal chemistry of a-hydroxy-b-amino acids. In Andrew B. Hughes (Ed.), Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4 - Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis Weinheim, Germany: Wiley. 2011, pp. 189-234.



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Queensland

Alliance for

Agriculture and

Food

Innovation


75

DR FEMI AKINSANMI

Queensland Alliance for Agriculture and Food Innovation Ecosciences Precinct, Boggo Road, Dutton Park Phone: 07 3255 4338 Email: [email protected]

ASSOCIATE PROFESSOR ANDRE DRENTH


Phylogenetic analysis of Pseudocercospora macadamiae Our previous study with PCR-RFLP has identified six genotypes in P. macadamiae populations from three geographical areas in Australia. This study will evaluate the phylogenetic relationship between isolates of P. macadamiae obtained from different cultivars in all the macadamia producing regions of Australia. Selected genes will be used to study sequence divergence among the P. macadamiae isolates and Pseudocercospora species. Sequence analysis will help to detect more fine scale genotypic diversity among P. macadamiae and enable a direct comparison of the species causing husk spot in macadamia and leaf spots in other hosts in Australia.




76

DR FEMI AKINSANMI


Microbial composition of macadamia husk Macadamia husks are lignocellulosic materials therefore, microorganisms including fungi as well as actinomycetes and other bacteria are able to colonise the tissue. Some of these microbes are important in bio-decomposition of the materials or other essential biological functions. This study will elucidate the microbial community dynamics on macadamia husks in relation to seasonality, fruit age and positional canopy height of the tree. AVAILABLE FROM 2016 SEM 2 AND 2017 SEM 1 Characterisation and diagnostics of blossom blight in macadamia Raceme blight also known as blossom or flower blight and grey mould are used to describe various diseases and disorders of macadamia flowers. Different fungi and oomycetes have been reported as causal agents of blossom blight in macadamia. In spite of distinct and remarkable differences in the pathogens, there is still lack of adequate knowledge of the symptom development and disease epidemiology for each pathogen-host interaction. This study will examine the etiology of the disease and establish the epidemiological conditions necessary for infection. The scholar will use plant pathology research techniques and gain advanced plant science and molecular skills. It is expected that the scholar will contribute to publications from the research. Useful references: Phytopathology (1972) 62: 316-319; (1976) 66: 546-548 Development of LAMP assay to detect husk spot Husk spot is a unique disease of macadamia in Australia. The disease leads to premature abscission of macadamia nut. Existing conventional or traditional diagnostic method for husk spot is laborious and takes 4-6 weeks. Lack of diagnostic tool for early detection of infection before symptom expression hinders studies on infection process. Therefore, the aim of this study is to improve the detection and quantification of husk spot infection. The study will develop a simple and rapid diagnostic tool using the loop mediated isothermal amplification (LAMP) assay for early detection and characterisation of macadamia cultivars. The scholar will use existing DNA sequence data for husk spot fungus isolates to develop the LAMP assay. Scholars will gain advanced plant science and molecular skills and contribute to publications from the research. Useful references: Australasian Plant Pathology (2009) 38: 36-43; International Journal of Food Microbiology (2010) 140 183-191. How many Botryosphaeriaceae fungi are there in macadamia? Botryosphaeriacae fungi are of significant economic importance. They are major pathogens in several plant hosts in temperate, tropical and subtropical crops including macadamia, an Australian native plant. Many names based on morphological and host association are used to distinguish the species complex. However, these are mostly inaccurate. This project proposes to identify and classify the isolates, and based on molecular phylogenetic evidence, reveal distinct and new taxa in this species complex. This project will identify species within the family Botryosphariaecae that are associated with macadamia. The overall aim of the study is to determine if species of the Botryosphariaecae are able to inhabit macadamia tissues as ‘non-pathogenic’ fungi. The scholar will use general plant pathology research techniques including molecular tools to test the research hypotheses. Scholars will gain advanced plant science and molecular skills and contribute to publications from the research. Useful references: Australasian Plant Pathology (2009) 38: 36-43; International Journal of Food Microbiology (2010) 140 183-191.



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DR FEMI AKINSANMI


DR BRUCE TOPP

Queensland Alliance for Agriculture and Food Innovation Ecosciences Precinct, Boggo Road, Dutton Park Phone: 07 5453-5973 Email: [email protected]

Response of species and cultivars of Macadamia to Phytophthora cinnamomi Our previous study suggests that macadamia is tolerant to Phytophthora cinnamomi, however, in certain conditions the soilborne pathogen is able to cause significant damage to macadamia. This study will evaluate the resistance/susceptibility of Macadamia species and commercial cultivars to root rot and stem canker caused by P. cinnamomi.




78

DR KARINE CHENU

Queensland Alliance for Agriculture and Food Innovation (Toowoomba – Gatton) Phone: 07 4688 1357 Email: [email protected]

Understanding the basis of transpiration efficiency in wheat Wheat productivity is limited by the amount of biomass that plants can produce for the limited water supply they can access. Existing conditions in Australia and future predictions for increased temperature, evaporative demand and water scarcity enhance the need for higher transpiration-efficiency crops (“more crop per drop”). To breed for new wheat varieties with increased transpiration efficiency, the physiological responses of transpiration rate to environment need to be better understood. This work will use the new state-of-the-art UQ-Gatton lysimeter facility to investigate whole-plant and leaf-level transpiration rate and efficiency of contrasting wheat genotypes, and to characterise their response to evaporative demand and soil water status.



79

ASSOCIATE PROFESSOR RALF DIETZGEN

CILR, John Hines Building and QAAFI, Ritchie Bldg, UQ St Lucia Campus Phone: 07 3346 6503 Email: [email protected]

DR PAUL SCOTT


PROFESSOR PETER GRESSHOFF


Identification & characterization of viruses that infect the biofuel tree Pongamia pinnata Plant functional genomics research can benefit greatly from high throughput silencing of genes to determine their function(s) during development and defense against abiotic and biotic stress. Replicating viruses are efficient inducers of RNA silencing in plants and have been used extensively to silence plant genes in Arabidopsis, legumes, cereals and some horticultural crops. This project aims to identify and characterize viruses that infect P. pinnata trees to subsequently construct suitable viruses into virus-induced gene silencing (VIGS) vectors to allow functional genomic studies. Symptomatic and asymptomatic leaves will be collected from diverse locations and samples analysed by dsRNA extraction and gel electrophoresis analysis and by next generation high-throughput sequencing of total RNA.





80

ASSOCIATE PROFESSOR RALF DIETZGEN

Queensland Alliance for Agriculture and Food Innovation Ritchie Laboratories, St. Lucia Campus Phone: 07 3346 6503 / Email: [email protected] Website: http://www.qaafi.uq.edu.au//?page=157981

Molecular Plant-Microbe Interactions My research interest is in the discovery and biodiversity of genes, proteins and regulatory RNAs in plants and viruses and their interactions in agricultural systems. Increased knowledge of these molecular interactions will enable improved crop performance and better disease control. Special interests include the characterization of plant-adapted rhabdoviruses and tospoviruses, virus diagnosis and molecular evolution, taxonomy of negative-sense RNA viruses, RNA silencing pathways for pest and disease resistance, and functional genomics and molecular markers in tropical horticulture. Project 1: Characterization and control of a new rhabdovirus from lucerne. Rhabdoviruses are important pathogens of humans, animals and plants. Plant-adapted rhabdoviruses multiply in both their plant hosts and arthropod vectors. We aim to understand the molecular interactions in both hosts to devise better means of virus control. In this project you will participate in the analysis of the genome and genetic diversity of a new, economically important rhabdovirus from lucerne. The research includes development of a diagnostic assay to identify the natural host range and potential arthropod vectors. Virus-host protein interactions and cell-to-cell transport will be studied to gain insights into the virus’ replication and movement processes. In collaboration with colleagues in Argentina, we will also develop gene constructs for RNA silencing-mediated resistance and search for natural resistance genes in available germplasm. Project 2: Identification & characterization of viruses that infect the biofuel tree Pongamia pinnata. Plant functional genomics research can benefit greatly from high throughput silencing of genes to determine their function(s) during development and defense against abiotic and biotic stress. Replicating viruses are efficient inducers of RNA silencing in plants and have been used extensively to silence plant genes in Arabidopsis, legumes, cereals and some horticultural crops. This project aims to identify and characterize viruses that infect P. pinnata trees to subsequently construct suitable viruses into virus-induced gene silencing (VIGS) vectors to allow functional genomic studies. Symptomatic and asymptomatic leaves will be collected from diverse locations and samples analysed by dsRNA extraction and gel electrophoresis analysis and by next generation high-throughput sequencing of total RNA. This is a collaborative project with Professor Peter Gresshoff ([email protected]) & Dr. Paul Scott, Centre for Integrative Legume Research, School of Agriculture and Food Science. References: Dietzgen, R.G., Kuzmin, I.V. (eds.) (2012) Rhabdoviruses: Molecular taxonomy, evolution, genomics, ecology, host-vector interactions, cytopathology and control. Caister Acad. Press, Norfolk, UK, 276 pp, ISBN 978-1-908230-11-9 Martin, K.M., Dietzgen, R.G., Wang, R.Y., Goodin, M.M. (2012) Lettuce necrotic yellows cytorhabdovirus protein localization and interaction map and comparison with nucleorhabdoviruses. Journal of General Virology 93: 906-914. Dietzgen, R.G., Martin, K.M., Anderson, G., Goodin M.M. (2012) In planta localization and interactions of impatiens necrotic spot tospovirus proteins. Journal of General Virology 93: 2490-2495. Klein-Marcuschamer, D., Turner, C., Allen, M., Dietzgen, R.G., Peter Gray, Gresshoff, P.M., Hankamer, B., Heimann, K., Scott, P., Speight, R., Stephens, E., and Nielsen, L.K. (2013) Technoeconomic analysis of renewable aviation fuel from microalgae, Pongamia pinnata, and sugarcane. Biofuels, Bioproducts & Biorefining: doi: 10.1002/bbb.1404. Biswas, B., Kazakoff, S.H., Jiang, Q., Samuel, S., Gresshoff, P.M., and Scott, P.T. (2013) Genetic and genomic analysis of the tree legume Pongamia pinnata as a feedstock for biofuel. Genome Biology (in press).


http://www.qaafi.uq.edu.au/?page=157981


81

DR ANDREW GEERING

Queensland Alliance for Agriculture and Food Innovation Ecosciences Precinct, Boggo Road, Dutton Park Phone: 07 32554389 Email: [email protected]

ASSOCIATE PROFESSOR JOHN THOMAS Phone: 07 3255 4393 Email: [email protected]

Towards a better understanding of how plant pararetroviruses process proteins Banana streak virus (BSV) is a representative of the only group of pararetroviruses in plants. BSV is distantly related to Human immunodeficiency virus (HIV) although it is only infects plants. BSV has a simple replication strategy, producing the majority of the proteins it needs on one large polyprotein, which is then cleaved into functional units through the action of a virus-encoded aspartic protease. Retroviral aspartic proteases (APs) are unusual in that it is impossible to predict their substrate preferences through sequence analysis alone and cleavage sites must be predicted empirically. Recently, in our laboratory, we have determined the boundaries of the BSV capsid protein and using this information, made some predictions as to where the AP is cleaving. The next step in this line of research, which is the topic of this project, is to express the BSV AP in vitro and demonstrate cleavage using synthetic peptides as substrates.




82

DR JIM HANAN

Biological Information Technology Group Queensland Alliance for Agriculture and Food Innovation Phone: 07 3365 8234 Email: [email protected]

Towards better fruit and nut yields: Understanding tree architecture This project will take a computational modeling approach to understanding the dynamics of tree architecture in a selected tropical or sub-tropical fruit or nut tree species. After reviewing what is known about the flushing and flowering of the selected species, data on tree architecture will be collected, and a virtual plant model will be developed. Functional aspects of interest may also be incorporated.



83

ASSOCIATE PROFESSOR ELIZABETH AITKEN

School of Agriculture and Food Sciences St Lucia campus, The University of Queensland Phone: (07) 3365 4775 Email: [email protected]

DR LEE HICKEY

Queensland Alliance for Agriculture and Food Innovation Phone: (07) 3365 4805 Email: [email protected]

Simultaneous selection for resistance to crown rot and foliar diseases in barley Crown rot, caused by the pathogen Fusarium pseudograminearum, is an important disease of winter cereals such as wheat and barley. This project aims to develop a high-throughput phenotypic screening assay that enables simultaneous selection for resistance to crown rot and foliar diseases (e.g. leaf rust caused by Puccinia hordei Otth., and spot form of net blotch caused by Pyrenophora teres f. maculate) in segregating populations of barley grown under controlled environmental conditions. The screening assay will incorporate rapid generation advance techniques for the purpose of accelerating breeding cycles. Outputs of the Honours research project will be: 1) new screening methodology, 2) improved knowledge of the genetic control of resistance to crown rot in barley, and 3) germplasm enriched for the target traits, which will be a useful resource for further breeding efforts in Australia. The student will gain hands-on experience in pathology, plant breeding and genetics.




84

ASSOCIATE PROFESSOR ATHOL KLIEVE

BAgSc MRurSc PhD MASM UQ Gatton campus or Eco Science Precinct, Dutton Park Phone: 07 5460 1255 or 3255 4269 (Gatton) Email: [email protected]

DR JUSTIN GIBSON

BVSc PhD Phone: 07 5460 1830 Email: [email protected]

Naturally occurring bacteriocins; a novel therapy for the treatment of multidrug-resistant E.coli urinary tract infections in dogs This is a small project, with operating funds suitable for an honours project. It would suit a student who is interested in novel, non-antimicrobial treatments of bacterial infections. The overall aim of this research is to detect, isolate and use naturally occurring bacteriocins to reduce or eliminate Multiple Drug Resistant (MDR) Escherichia coli in the urinary tract of dogs, as an alternative to the use of antibiotics for the treatment and management of recurrent MDR cystitis. The Honours project will be the first step in this process and involves the isolation and characterisation of bacteria that produce bacteriocins. Techniques that will be gained through the project will be both traditional microbiology and molecular biology based.




85

DR MARY FLETCHER

Health and Food Sciences Precinct, Coopers Plains Phone: 07 3276 6089 Email: [email protected]

Project 1: The prevalence of indospicine in Indigofera plant species by LC-MS/MS The amino acid indospicine is an arginine-analogue found only in Indigofera plant species and has been shown experimentally to be hepatotoxic in a number of animal species. Indospicine is an unusual amino acid in that it is not incorporated into proteins, but is present as the free amino acid. Indospicine accumulates as the free amino acid in tissues of animals fed Indigofera plant material, and such residues have been shown to persist for several months after cessation of feeding. Dogs are particularly sensitive to the hepatotoxic affects of indospicine, and canine fatalities have been reported from the consumption of indospicine contaminated meat from both camels and horses grazing Indigofera plants in central Australia. Indigofera plant species are generally quite palatable with good nutritive value, and have been proposed as potentially valuable forage species. However, the presence of indospicine has limited this potential with high intake of Indigofera shown to have hepatotoxic effects in grazing animals including cattle. This is a laboratory-based project investigating the prevalence of indospicine in a range of Indigofera plant species, and will involve the extraction and chemical analysis of plant samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Project 2: Investigating the Cause of Cleft Palate in Spectacled Flying Fox The spectacled flying fox (Pteropus conspicillatus) is a native species with limited distribution in north-eastern Queensland and feeds on fruits and blossom of a wide range of vegetation. The increasing occurrence of cleft palate in flying fox pups is one factor which threatens the survival of this “vulnerable” species. This project will investigate the links between the occurrence of cleft palate and the consumption of fruit of wild tobacco Solanum mauritianum, a source of the teratogenic steroidal alkaloid solasodine. The project will collaborate with wildlife scientists and volunteers who will provide samples of plant material and animal bloods for analysis by liquid chromatography mass spectrometry (LC-MS) by the student. A background in chemistry with some knowledge of mass spectrometry is essential for this project, as well as an interest in applying such skills to address an ecological problem.

This project will be located at the Health and Food Sciences Precinct at Coopers Plains, Brisbane. (http://www.qld.gov.au/dsitia/science/assets/documents/health-food-sciences-precinct-brochure.pdf ) in the laboratory of Dr Mary Fletcher (QAAFI-UQ). http://www.qaafi.uq.edu.au/fletcher-dr-mary


http://www.qld.gov.au/dsitia/science/assets/documents/health-food-sciences-precinct-brochure.pdf

http://www.qaafi.uq.edu.au/fletcher-dr-mary


86

DR MANUEL RODRIGUEZ VALLE

BBIOTECH/PhD Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia. Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072 Phone: 07 3255 4529 Email: [email protected]

DR ALA LEW-TABOR

PhD Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia. Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072 Phone: 07 3255 4535 / Mobile: 0417 737 595 Email: [email protected]

Harnessing the genome of the Australian paralysis tick to develop effective control products Ixodes holocyclus (paralysis tick) occurs along the eastern coast of Australia from far north Queensland to southern Victoria and is the most virulent tick species in terms of paralysis. Each year I. holocyclus affects ~100 000 domestic animals, with up to 10 000 companion animals. Also, humans are affected by tick bites provoking hypersensitivity reactions. Toxin is produced as the adult female tick engorges and paralysis is frequently induced just prior to detachment. In this research project a transcriptome analysis of salivary glands and viscera samples dissected from fully-engorged I. holocyclus ticks was conducted. cDNA was synthesised from ticks collected from bandicoots or dogs and cats with paralysis symptoms. The cDNA was analysed by 454 and Illumina technologies. Seventeen transcripts related with toxins were found within the samples under study. The transcriptome information acquired from the I. holocyclus tick conforms a unique database for the paralysis tick stored at the Centre for Comparative Genomics, Murdoch University. Holotoxins1, 2 and 3 were cloned into the Pichia pastoris vector for expression, and purification for animal screening. Other studies need to be conducted to find other proteins directly related with paralysis tick symptoms. Therefore, in the framework of an ARC linkage grant, the development and screening of a display library prepared from I. holocyclus salivary gland cDNA is proposed. The cDNA will be cloned into the yeast vector pYD1 for the expression of paralysis tick proteins on the surface of Saccharomyces cereviseae. The recombinant yeast which express proteins associated with the host – parasite interaction and paralysis tick symptoms will be selected using fluorescence activated cell sorting (FACS). Hyper immune sera obtained from dogs resistant to paralysis tick will be utilised for sorting the recombinant yeast by FACS. Selected recombinant transformants will be used for expression, purification and analysis for optimal expression of the recombinant proteins in liquid cultures. Finally, the recombinant proteins will be tested in animals to determine their capability to protect against paralysis symptoms. Synaptosome and neuronal cell receptor assays need to be developed in order to examine the mechanisms of paralysis toxin(s). We are seeking post-graduate students (Honours, Masters, PhD) to contribute to this exciting research program.




87

DR MANUEL RODRIGUEZ VALLE

BBIOTECH/PhD Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia. Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072 Phone: 07 3255 4529 Email: [email protected]

Serine Protease Inhibitors of Rhipicephalus microplus (Cattle tick) expressed in transgenic plants. Proteases are very important molecules implicated in the protection and survival of different organisms against pathogenic entities that include virus, insects and other parasites. An overexpression or higher concentrations of these proteases can lead to potentially damaging of these organisms. Some insects and many of the phytopathogenic microorganisms secrete extracellular proteases causing proteolytic degradation of proteins which is directly related with their pathogenesis. However, plants have generated different defense mechanism to inhibit proteolysis activity in these pathogenic organisms such as secretion of specific proteases inhibitors. In most plants, natural mechanisms to control insect attack include protease inhibitor (PI) accumulation [1]. Additions of PIs to insect diets have been shown to limit insect development [2-4]. The overexpression of PI's in transgenic plants may decrease virus and insect damage. Researches effort conducted previously have demonstrated that the expression of PIs in plant is an environmentally sound method of pest control [5, 6]. Aim: The expression in plants of serine protease inhibitor of R. microplus (Cattle tick) can reduce the pathogenic effect of virus and insects in these transgenic plants. References 1. Ryan CA: Proteolytic enzymes and their inhibitors in plants. Ann Rev Plant Physiol 1973, 24:173 -

186. 2. Gatehouse AMR, Gatehouse, J.A., Boulter, D.: Isolation and characterization of trypsin inhibitors

from cowpea. Phytochemistry 1980, 19:751-756. 3. Hilder VA, Gatehouse, A.M.R., Sheerman, S.E., Barker, R.F., Boulter, D.: A novel mechanism of

insect resistance engineered into tobacco. 1987, 330:160-163. 4. Johnson R, Narva6z, J., An, G., Ryan, C.A. : Expression of proteinase inhibitors I and II in transgenic

tobacco plants: effects on natural defense against Manduca sexta larvae. Proc Nat Acad Sciences 1989, 86:9871-9875.

5. Thomas JC, Adams DG, Keppenne VD, Wasmann CC, Brown JK, Kanost MR, Bohnert HJ: Protease inhibitors of Manduca sexta expressed in transgenic cotton. Plant cell reports 1995, 14(12):758-762.

6. Alvarez-Alfageme F, Maharramov J, Carrillo L, Vandenabeele S, Vercammen D, Van Breusegem F, Smagghe G: Potential use of a serpin from Arabidopsis for pest control. PLoS ONE 2011, 6(5):e20278.



88

DR SUSHIL DHITAL

Centre for Nutrition and Food Sciences (CNAFS) Queensland Alliance for Agriculture and Food Innovation (QAAFI) ARC Centre of Excellence in Plant Cell Walls Room S426, Hartley Teakle Building, The University of Queensland Phone: 07 334 67373 Email: [email protected]

Bakery products such as biscuits, cakes and breads are widely consumed processed foods in western society. The major ingredients in bakery products are wheat flour, the other ingredients being fat, sugar etc. On consumption of bakery products, the starch in wheat flour is rapidly digested increasing the postprandial blood glucose level, which might have a negative health effect and is often associated with type II diabetes. This project aims to formulate low fat and low sugar bakery products incorporated with enzyme resistant starch (ERS) and investigate the textural attributes of the baked products as well as change in morphological and micro structure of starches in bakery products.


biotechnology research projects 2016

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