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Honours Projects for 2015
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SCHOOL OF CHEMISTRY AND FORENSIC SCIENCE
Bachelor of Science (Honours) in Applied Chemistry
2015 PROJECTS
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The value of an Honours degree
An Honours degree provides an opportunity to be involved in a research program in an area that
interests you, and provides training in research techniques and experience with modern research
instrumentation. The Honours programme adds a new dimension to the skills that you have acquired
during your undergraduate years and enhances your immediate employment prospects and, more
significantly, your future career potential. An Honours degree provides a pathway to postgraduate
research degrees (MSc or PhD), with possible financial support from an Australian Postgraduate
Award (APA) or some other postgraduate scholarship.
Eligibility
Applicants must have completed a UTS recognised bachelor's degree in a relevant discipline at an
appropriate level. The honours program is normally open to students who have attained at least a
credit average over the final two-thirds of the undergraduate program..
Assessment
In the Honours year, students undertake original research projects under the supervision of
academic staff. Students write a thesis about the project and present a talk on the outcomes. There
is also a coursework component, with assessment tasks on advanced chemistry topics.
Choosing a project
It is advisable to contact a potential supervisor and discuss a project during the semester prior to
enrolment in the Honours project. A number of research projects are on offer in the school and are
outlined in this booklet. Feel free to discuss any of these with the appropriate supervisor.
If you have an interest in carrying out a project in an area that is not listed, it may be possible to
arrange suitable supervision. For instance, a number of previous students have carried out their
work-based projects in conjunction with the CSIRO, ANSTO or an industrial partner.
How to apply
After discussing deciding on a project with a supervisor, fill out the forms available at:
http://www.uts.edu.au/future-students/science/go-further/honours-program/school-chemistry-and-
forensic-science-honours
Applications should be submitted by November 28, 2014 to be considered for a first round offer, but
final round applications are accepted until January 31, 2015. Students generally begin work on their
project in February. There are Autumn and Spring semester intakes for the programme.
Advice
If you have any questions about the programme, please feel free to discuss them with the Chemistry
Honours Coordinator, A/Prof. Andrew McDonagh ([email protected]).
Honours Projects for 2015
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Title Screening for lung infections: volatile profiling of Pseudomonas
aeruginosa in cystic fibrosis patients
Nature of problem
work is intended to
address
Chronic Pseudomonas aeruginosa infection is a
hallmark of cystic fibrosis lung disease (see
image). Current techniques used to screen
patients for this infection are both cumbersome
and highly invasive. New techniques involving
the chemical analysis of volatile biomarkers in
breath samples have demonstrated their potential
as non-invasive screening tools. Importantly, Pseudomonas bacteria have a
distinct metabolism which can produce bacteria-specific volatile organic
compounds (VOCs) in exhaled air, allowing for rapid diagnosis and
treatment.
This project will chemically profile the VOCs produced by P. aeruginosa
which are characteristic of chronic lung infections in cystic fibrosis patients.
The results of the project will assist in determining bacteria-specific
biomarkers which can be used as a screening tool for detecting lung infection
in cystic fibrosis patients. This information will assist with the long term goal
of developing a portable instrument which can rapidly detect this infection on
the breath of cystic fibrosis patients.
Outline of
goals/objectives
The goals of this project are as follows:
To optimise a gas chromatography-mass spectrometry method for the
analysis of volatile compounds produced by P. aeruginosa
To compare the volatile profiles of breath samples collected from a
control group with a clinical group of cystic fibrosis patients
To identify P. aeruginosa specific volatile biomarkers which can be
used to rapidly screen cystic fibrosis patients for bacterial lung
infection
UTS supervisor Professor Shari Forbes
External supervisor Clinical Associate Professor Peter Middleton (Westmead Millennium
Institute for Medical Research, University of Sydney)
Contact information [email protected]
Honours Projects for 2015
8
Title Profiling the Scent of Training Aids for Blood-detection Dogs
Nature of problem
work is intended to
address
Blood-detection dogs are a specialised scent-
detection canine trained to detect the scent of
latent blood at a crime scene. Their
sensitivity is superior to presumptive chemical
tests in identifying the presence of both
visible and latent blood traces. Blood-
detection dogs are trained on a variety of
training aids including fresh human blood,
degraded cadaver blood, and animal blood.
It is currently unknown what chemical scent is produced by these training
aids and whether they produce different scent profiles recognisable by the
dogs. Police dog units have reported different responses from the dogs based
on the type of blood used during training. It is important to identify the
chemical differences in blood scent to ensure the dogs are being trained on
the most typical scent they will encounter at a crime scene.
Outline of
goals/objectives The purpose of this project is to chemically profile fresh human blood,
degraded cadaver blood, and a range of animal blood samples to
compare their chemical scent profiles.
The headspace of the blood samples will be collected using solid phase
micro-extraction (SPME) and analysed by gas chromatography-mass
spectrometry.
The chemical scent profile will be compared to the response of the
blood-detection dog during training.
Special requirements Ethics approval for the use of blood samples
Industry/Ext partner NSW Police Force Dog Unit
UTS supervisor Professor Shari Forbes, Dr Katie Nizio
Contact information [email protected]
Honours Projects for 2015
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Title Decomposition chemistry: establishing the volatile profile of human
remains during the early post-mortem period
Nature of problem
work is intended to
address
Following a natural or man-made disaster, search and rescue teams are
rapidly deployed to locate both living and deceased victims. Once the living
have been located, the task of the search team becomes more challenging as
they seek to locate victim remains in the disaster scene. Cadaver-detection
dogs are often used to locate victims in mass disaster investigations however
this presents a challenging environment as it is not known whether the scent
of a recently deceased victim resembles the living (human scent) or the dead
(decomposition odour).
The aim of this project is to chemically analyse soft tissue to determine the
volatile profile immediately after death and during the early postmortem
period, mimicking the timeframe when victims are typically recovered from
mass disasters. This profile will be compared to the literature available about
human scent to determine similarities or differences with respect to ante-
mortem and post-mortem volatile profiles.
Outline of
goals/objectives
The goals of this project are as follows:
To optimise a method for collecting volatile samples from soft tissue
To analyse the volatile samples using gas chromatography-mass
spectrometry
To determine variations in the postmortem volatile profile over time
To conduct a literature review of human scent and compare the ante-
mortem and post-mortem volatile profiles
UTS supervisor Professor Shari Forbes and Dr Katie Nizio
Contact information [email protected]
Honours Projects for 2015
10
Title Silica Hydrothermal Synthesis of Amorphous from Industrial Wastes
Project Description Amorphous silica is a growing commodity product used in a range of applications such
as high surface area fillers for rubber in car tires resulting in significantly reduced fuel
consumption to use as a thickening agent in toothpastes and cosmetics. Due to the
high surface area and porosity, amorphous silica also has potential application as
catalysts supports and may be used in a range of nutrient and drug delivery
applications. Currently, silica is sources through the calcining of quartz at high
temperature in the presence of soda to form a water soluble silica glass which is then
neutralised to precipitate the high surface area amorphous silica. The high
temperature route results in high energy consumption which can be avoided if
hydrothermal (autoclaving) techniques are employed.
Hydrothermal methods for the production of waterglass (soluble silica glass) from
aluminosilicates are known, but are not currently commercially available. This study
proposes to investigate the conditions of hydrothermal synthesis of silica waterglasses
by autoclaving aluminosilicate industrial wastes such as fly ash, bottom ash and
pitchstone fines in the presence of sodium hydroxide. Subsequent precipitation of the
silica with nitric acid yields high surface area high purity amorphous silicas. Methods of
characterisation will be Raman spectroscopy which is sensitive to silica structure, gas
adsorption to determine surface area and porosity characterisation and differential
scanning calorimetry which can also be applied to porosity characterisation. Scanning
electron microscopy will also be pursued.
In addition to the high surface area silica, by-products of the process are
aluminosilicates which depending on the hydrothermal conditions can yield zeolites.
Zeolites are important minerals in that they have many industrial applications in
particular catalysis. These aluminosilicate by-products will be characterised by Raman
spectroscopy, crystallography and thermogravimetric analysis.
Supervisor Dr Paul Thomas
Contact information [email protected]
Honours Projects for 2015
11
Title Calorimetric Investigation of the Hydration of High Sulphate Cement at
Elevated Temperature
Project Description Precast concrete elements are commonly manufactured for the construction of
bridges, tunnels, culverts, pipes and drains as high strength elements and are cured
at elevated temperature within a 24 hour period (as oppose to 28 days at ambient
temperature). The chemistry of the cement curing, however, is altered by the use of
elevated temperature. In particular, the hydration of tricalcium aluminate (C3A)
present in cement as a by-product of clinker process is affected. C3A hydrates rapidly
on the addition of water and is extremely exothermic causing acceleration of
Portland cement hydration. The hydration of the C3A may be inhibited by reaction of
the hydrated C3A with sulphate to form the mineral ettringite. Sulphate is added
typically in the form of gypsum which is interground with the cement clinker, a glassy
calcium silicate formed in the kiln during cement manufacture. The sulphate ions
react with the calcium aluminate hydrate to form ettringite which inhibits further
hydration of the calcium aluminate through the formation of an impermeable layer.
In the manufacture of precast concrete elements at elevated temperature, however,
the sulphate becomes more soluble and the ettringite decomposes as the sulphate is
dissolved into solution. Further hydration of the C3A results in increased temperature
and flash setting of the cement. At elevated temperature the formation of ettringite
is inhibited by the solubility of the sulphate, however, after curing, and once the
temperature has returned to ambient, the solubility of the sulphate decreases and
sulphate becomes available once again for ettringite formation. This delayed
ettringite formation, which is accompanied by a large volume increase, occurs in the
hardened state and can result in the cracking and failure of precast concrete
elements. In order to prevent these deleterious processes from occurring, an
understanding of the formation conditions is necessary. This project, therefore,
investigates the reaction chemistry of high sulphate cements at elevated
temperature using adiabatic calorimetry and differential scanning calorimetry in
conjunction phase analysis using crystallography. A greater understanding of the
reactions involved, in particular in the formation of delayed ettringite, will help to
minimise hazardous degradation of precast concrete elements in construction.
Supervisors Paul Thomas (CFS), Kirk Vessalas (Civil Engineering)
Additional Information Financial Support for this project is available through industrial funding from
Humes Australia.
Contact information Please contact Paul Thomas ([email protected]) for further details.
Honours Projects for 2015
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Title The Influence of the Composition of Supplementary Cementitious Materials (SCM)
In mitigating Alkali Silica Reaction (ASR)
Project Description Alkali Silica Reaction (ASR) is caused by slow reactions of alkalis from Portland
cement and certain reactive silica in aggregates. ASR can cause expansion and
premature deterioration of concrete structures. This potential reaction is
traditionally detected by accelerated expansion tests of cement mortar and concrete
by means of increasing the availability of alkali and temperature. Two such test
methods have recently been agreed and published by Standards Australia in 2014.
A range of supplementary cementitious materials (SCM), such as fly ash and ground
granulated blast furnace slag (slag), have been found effective in mitigating the ASR.
The effectiveness of an SCM to mitigate ASR appears to depend on its composition,
its dosage and the degrees of reactivity of the aggregate. This study will investigate
the influence of the composition of SCMs and other physical properties on the ASR
and the kinetics of the reaction in cement mortar and/or concrete with and without
the SCM. The outcomes will provide guidance on the selection of SCMs based on
their composition in ASR mitigation.
Supervisors Paul Thomas (CFS), Kirk Vessalas (Civil Engineering)
Additional Information Financial Support for this project has been informally approved through the Centre
for Built Infrastructure Research (CBIR) and Cement and Concrete Aggregates
Australia (CCAA).
Contact information Please contact Paul Thomas ([email protected]) for further details.
Honours Projects for 2015
13
Title The detection of clandestine drugs in polymers: GC-MS profiling of
volatile compounds available to drug-detection dogs
Project Description There exists a variety of approaches by smugglers to move drugs across
borders. Attempts have been made to transport drugs, such as cocaine, by
disguising an odour that could be potentially detected by trained drug-
detection dogs. Drugs are often wrapped in plastic bags or materials, but now
smugglers are attempting more sophisticated approaches that involve the
impregnation or dissolution of drugs into polymer matrices in the belief that
detection will be more difficult. The drugs are then extracted in clandestine
laboratories.
This project will involve the development of an analytical method to
determine if the odour of the drug can be detected when incorporated into
common polymers. Two dimensional gas chromatography- time-of-flight
mass spectrometry (GC x GC - TOFMS) will be used to identify
characteristic volatiles that may prove to be effective markers for the
detection of particular drugs hidden in polymers. The volatile profile will be
correlated to the response of drug-detection dogs to similar samples.
Outline of
goals/objectives
The goals of this project are as follows:
To optimise a method for collecting and analysing volatile samples
from drug impregnated polymers using two dimensional GC-MS
To identify the volatile profile that is available for detection by drug-
detection dogs
To compare the volatile profile with the response of drug-detection
dogs when exposed to drug-impregnated polymers
Supervisors Prof. Shari Forbes, A/Prof. Barbara Stuart, Dr Shanlin Fu and
Dr Mark Tahtouh (Australian Federal Police)
Contact information [email protected], [email protected]
Honours Projects for 2015
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Title Chlorinated nucleosides - novel mediators or biomarkers of disease?
Project Description Chlorine is a potent disinfectant, which is present in aqueous solution, as hypochlorous acid (HOCl), and molecular chlorine (Cl2). Although used widely to kill harmful bacteria in both drinking water and swimming pools, it is also responsible for the formation of numerous disinfection by-products (DBPs), which can modify DNA, and have been implicated in cancer development. HOCl is also produced in the body by activated leukocytes via the myeloperoxidase-catalysed reaction of H2O2 with Cl- ions. The chemistry of HOCl in biological systems has attracted considerable attention, as excessive or misplaced production of this oxidant during prolonged inflammation, damages tissue and causes disease. HOCl chlorinates the nucleoside building blocks of RNA and DNA, and these products are seen in diseased tissue. Currently it is not known whether RNA / DNA chlorination is simply a consequence of the disease process, or whether these modified nucleosides play a role in disease pathology.
This project will build on our novel data showing that chlorinated nucleosides perturb the expression of key stress and toxicity genes, which has a significant impact on cellular function. These cellular changes are detrimental to function, and may play a role in disease development. This has important toxicological significance for chlorinated drinking water supplies, in addition to providing novel insights into inflammation-induced disease. We will use a mass spectrometry approach to assess the extent and rate of uptake and turnover of chlorinated nucleosides by different human vascular cells and a molecular biology approach to define the consequences of chlorinated nucleosides on vascular cell function.
Supervisors: Dr Shanlin Fu (University of Technology Sydney), Associate Professor Clare Hawkins (The Heart Research Institute, Sydney)
Honours Projects for 2015
15
Title Radical-Mediated Protein Damage: Products, Mechanisms and Consequences
Project Description Free radicals are generated in biological systems as by-products of normal cellular
redox processes, or via the interaction of cells and tissues with a number of external
agents (e.g. smoke, radiation, asbestos, drugs). It is well established that amino acids,
peptides and proteins are major targets for radicals, with protein oxidation occurring
during the normal aging process, and in various human diseases including
atherosclerosis (hardening of the arteries) and cataracts. Free-radical mediated damage
to proteins is also relevant to the food, agricultural and pharmaceutical industries, as it
is involved in plant stress, food spoilage and sterilisation of foods/pharmaceuticals
(using radiation). Numerous radical species (e.g. hydroxyl (HO), peroxyl (ROO
),
superoxide (O2)) can be generated in these systems, but their reactivity differs
widely. Aromatic amino acid side chains (e.g. tyrosine (Tyr), tryptophan (Trp),
histidine (His)) are well established targets for radical damage, and the formation of
diTyr crosslinks results in radical-induced protein aggregation. However, recent data
indicate that alternative mechanisms and products that involve Trp radicals are also
likely to be important in these processes.
This project will initially focus on the characterisation of products generated on a well-
defined series of Trp-containing peptides that have been exposed to a variety of radical
generating systems. The aim of the project will be to identify and characterise novel
products (e.g. dimeric species) and quantify their abundance relative to established Trp
oxidation products (e.g. kynurenine, N-formyl-kynurenine). The results obtained from
initial studies of simple model peptides will be extended to more complex
peptides/model proteins as well as proteins that are relevant to the development of
human disease. The data will enable the potential development of novel biomarkers for
evaluating the contribution of radical-induced damage in disease processes. A further
direction for the project will be to examine the efficacy of novel antioxidants in
preventing or reversing this damage.
This project will use a wide variety of analytical chemical methods, including UV/Vis
spectroscopy, EPR spectroscopy, mass spectrometry (MS), HPLC/UPLC and LC/MS,
as well as some biochemical approaches e.g. cell culture, gel electrophoresis. This
project would suit someone with a chemistry/biochemistry background with a strong
interest in analytical and protein chemistry.
Supervisors: Dr Shanlin Fu (University of Technology Sydney)
Dr David Pattison (The Heart Research Institute, Sydney)
Honours Projects for 2015
16
Title Pesticide Residue Testing, Analysis for Australian Grown Fruits and Vegetables
Using QuEChERS, QQQ LC-MS and QTOF LC-MS Techniques
Project Description Most vegetable products available in local grocery stores are grown using
conventional agricultural practice involving the use of pesticides. Pesticide residues
in food continue to be the target of studies due to the uncertainty concerning adverse
effects of those residues on human health after a lengthy exposure at low levels.
More than 1000 active ingredients have been utilised and are formulated in thousands
of different commercial products. They include a variety of compounds, mainly
insecticides, herbicides and fungicides, with very different physico-chemical
characteristics and large differences in polarity, volatility and persistence.
Consequently, in order to ensure food safety for consumers and to facilitate
international trade, regulatory bodies around the world have established maximum
residue levels (MRLs) for pesticide residues in food commodities; that is, the
maximum amount of pesticide residue and its toxic metabolites allowed on a
commodity should not be exceeded if good agricultural practice is adhered to during
the use of the pesticide.
In this project, the QuEChERS (Quick-Easy-Cheap-Effective-Rugged-Safe) sample
preparation technique developed by Anastassiades et al. will be used to extract
pesticide residues from fruits and vegetables followed by a dispersive solid phase
extraction clean-up of the extract. The extract will be then analysed by both QQQ
LC-MS and Q-TOF LC-MS.
Supervisors
Dr. Shanlin Fu and Dr. Linda Xiao
Honours Projects for 2015
17
Title Design of precursor molecules for electron beam induced nano-chemistry
Project description Electron beam induced chemistry (EBIC) is a cutting edge technique for the fabrication and editing of advanced functional materials at the nano-scale. Emerging EBIC applications include the fabrication of next-generation optoelectronic devices made from diamond, chemical manipulation of single photon emitters (Fig. 1), and electrical contacting of carbon nanotubes.
In order to expand the applications of EBIC, understanding of the underlying chemical pathways and reaction mechanisms must be improved. Recent advances made at UTS have made it possible to identify the properties of precursor molecules that lead to extraordinary EBIC performance. The present project will use this knowledge to design, synthesize and test a new generation of precursor molecules. The honours student will focus on the design and chemical synthesis phases of the project, and will have the opportunity to collaborate with a team of PhD students working on EBIC development and applications of the synthesized precursors.
Figure 1: Chemical switching of the quantum states of single photon emitters by EBIC. The emitters are embedded in nanoparticles processed by a scanned electron beam.
Supervisors Prof. Milos Toth, Dr. Charlene Lobo, Dr Andrew McDonagh
Contact information [email protected]
Honours Projects for 2015
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Project title Characterization of the activities of model catalyst microarrays fabricated using electron beam induced chemistry
Project description Electron beam induced deposition is a new technique for fabricating nanoscale devices and sensors in which a substrate is irradiated in the presence of a gas that contains the atoms of interest. The electron beam dissociates surface-adsorbed (rather than gas-phase) precursor molecules, thereby leading to highly localised ‘3D printing’ of structures with a spatial resolution of ~10 nm.
This project will build on recent work on e-beam fabrication of high purity Pt nanoparticle arrays (C. Elbadawi, M. Toth & C. Lobo, ACS Appl. Mat. Interfaces, 2013) by investigating their activity for key catalytic reactions such as the oxidation reduction reaction in fuel cells, and reduction of CO2 to carbon-based fuels. The project will involve assessment of the activities of e-beam fabricated Pt films and microarrays by cyclic voltammetry. Characterization of the structure and electronic states of the catalyst particles will also be conducted using synchrotron x-ray diffraction and x-ray photoelectron spectroscopy. The project will be conducted in close collaboration with physics PhD students involved in fabrication of the arrays and characterization of their properties by complementary techniques.
Experimental techniques
Cyclic voltammetry, synchrotron x-ray diffraction, XPS
Supervisor Dr. Charlene Lobo A/Prof Andrew McDonagh
Contact information [email protected]
Honours Projects for 2015
19
Title Alkaloid-like molecules: AChE inhibitors as potential treatment of
Alzheimer’s disease
Description Background Our earlier work on the Bridging Ritter reactions of natural products such as limonene with a variety of nitriles under Bridging Ritter reaction conditions, provided cyclic imine 1, in one single step. Cyclic imines have been used in our group to generate alkaloid-like compounds for drug discovery. These alkaloid-like compounds were shown to be strong AChE inhibitors. One of the primary roles of acetylcholinesterase (AChE) is the hydrolysis of the neurotransmitter acetylcholine (ACh) to inactive choline and acetate in cholinergic synapses. Reversible AChE inhibitors, for example, the natural alkaloid Galanthamine (Reminyl), is an approved drug for the treatment of Alzheimer’s disease (AD).4
(a) Synthesis of cyclic imine 1(b) Galanthamine in the AChE catalytic site. Synthesis The cyclic imine 2 will be synthesis, using our standards condition from (+)-limonene. These compounds will be used as the central intermediates, in two sequential steps of reduction and reductive alkylation, to generate novel and relatively complex alkaloid-like molecules. Biological assays Since the natural alkaloids often exhibit a rich spectrum of biological activity, and it would be likely the case for the alkaloid-like molecules.5 Therefore the potential biological activity of synthesised compounds will be assessed for AChE inhibitory activity.
Project aims 1. To synthesise optically active cyclic imine 1 from (R)-(+)-limonene, via the Bridging Ritter reaction.
2. To synthesise alkaloid-like compounds from imine 1. 3. To assess the biological activities of synthesised compounds for AChE
inhibitory activity 4. To assess SAR (structure activity relationship) of synthesized compounds via
computer-aided molecular modeling study.
Supervisor A/Prof. Alison Ung
Honours Projects for 2015
20
Title Discovery of AChE inhibitors using STD NMR
Project Description
Background One of the primary roles of acetylcholinesterase (AChE) is the hydrolysis of the neurotransmitter acetylcholine (ACh) to inactive choline and acetate in cholinergic synapses. Reversible AChE inhibitors such as the natural alkaloid Galanthamine (Reminyl) is an approved drug for the treatment of Alzheimer’s disease (AD). The object of this medicinal chemistry project is to understand the molecular interactions between AChE inhibitors and the enzyme which would assist in discovery of useful AChE inhibitors suitable for drug development for the treatment of AD.
Practical aspects of STD NMR in drug screening The simplicity of the Saturation transfer difference (STD) NMR method allows for adaptability to an array of different compound interactions. Its practicality in ligand screening versus other methods makes it very useful technique for investigating protein-ligand interaction in solution. The technique can be easily implemented on our existing 500MHz Agilent NMR using Biopack® protocols.
The technique provides the mapping of the binding epitopes (ISTD = Io – Isat) of the ligand (inhibitor) in the binding pocket of the protein (i.e. AChE enzyme). I
The technique further allows the dissociate constant (KD) to be determined according to Eq. 1.
Figure 1. The selective saturation of receptor signals is obtained from the transfer of saturation from the protein to the ligand (green A, B, C). Intensity of the signal is increased for parts of the ligand that are in closest contact with the protein when binding (B). Figure 2. The spectrum of the selective saturation of receptor signals (Isat) is subtracted from the 1H NMR reference spectrum (IO) to yield the difference spectrum (ISTD=IO-Isat).
eq.1
Project aims the qualitative manner in which an AChE inhibitor binds to the enzyme,
ligand mapping via a direct characterisation of moieties of ligand interaction through identification of the individual protons of an inhibitor necessary for binding,
identify the specific binding pocket within AChE enzyme;
and to determine the dissociation constant (KD) between the protein and the inhibitor.
Supervisor A/Prof. Alison Ung and Dr Ronald Shimmon
KD: Dissociation Constant
[E]: concentration of Enzyme
[L]: concentration of Ligand
Honours Projects for 2015
21
Title Synthesis of Benzopthiophene FtsZ inhibitors as antibiotics
Project Description The increase of antibiotic resistance among an array of bacteria is of growing concern in both hospital and community settings. Particularly, Methicillin-resistant Staphylococcus aureus (MRSA) has shown resistance towards traditional targets and every class of antibiotics available. In 2011, roughly 80,000 cases of methicillin-resistant S. aureus (MRSA) infections occurred in the United States alone.1
At this alarming rate, there is an urgent need of the new class of antibiotics. Over the years, the traditional targets have been exhaustively exploited and became ineffective. However, essential proteins necessary for bacterial cell division are a relatively new area of research to effectively kill bacteria and prevent infection by reducing cell viability and cell growth.2,3 FtsZ (Filamentous temp.-sensitive protein Z), is one such emerging target.2 Inhibition of FtsZ (de)assembly has been shown to cause bacterial cell death and reduced the MRSA in the animal model.
Computer-aided molecular modelling has indicated that our proposed benzothiophene 1 binds into the FtsZ pocket in the same manner as that the patented FtsZ inhibitor, PC1907234 (shown in ball and stick, with excellent ligand efficiency. Based on these results, a series of novel benzothiophenes targeting FtsZ will be synthesised and investigated for their antibacterial activity.
(a) (b)
Fig 1. (a) Simulated docking of benzothiphene 1 (grey stick model) into FtsZ pocket, PC (ball and stick model), (b) Benzothiophene 1 pose-view and detailed interactions in the binding pocket.
Project aims 1. To synthesise benzothiophene 1 and its analogues (Fig 1)
2. To determine antibacterial activity (MIC) of the synthesised compounds
against S. aureus
3. To explore the FtsZ inhibitory activity of the synthesised compounds
4. To investigate SAR (structure activity relationship) of the synthesised
compound via computer-aided molecular modelling
Supervisors Assoc. Prof Alison Ung and Prof Elizabeth Harry
Honours Projects for 2015
22
Title Functionalized fluorescent nanodiamonds for bioapplications
Project description Fluorescent nanodiamonds (NDs) have attracted much interest from the biological community as an ultimate agent for biomedical applications, such as biomarkers, drug and gene delivery and biocatalysts, owing to their chemical inertness, biocompatibility, prolonged photostability (negligible photobleaching) and low toxicity. Colour centres in diamond possess an unprecedented photostability and exhibits single photon emission at room temperature. NDs are excellent candidates for surface modification for applications in biology or medicine, as carbon can be readily modified with functional groups. However, the surface functionalization of NDs can affect the compatibility and toxicity of the carbon-based material within living cells. Hence, the aim of this project is to investigate the effect of various surface functionalities of NDs upon interaction with living cells.
Techniques Confocal laser scanning microscopy, fluorescence microscopy, dynamic light scattering, zeta potential, FTIR, scanning electron microscopy, tissue culturing
Supervisors Dr Olga Shimoni, Dr Andrew McDonagh
Contact [email protected]
Honours Projects for 2015
23
Titles 1: Radiolabel AChE inhibitors as PET probes for imaging cerebral AChE.
2: Developing AChE substrate-type as PET radioprobes for measuring AChE activity.
Project description Background The central cholinergic system plays an important role in several brain functions, such as attention, memory, cognition, and consciousness. Acetylcholine-mediated neurotransmission within cholinergic synapses in the brain is terminated by the breakdown of the neurotransmitter acetylcholine (Ach) into the inactive components, by the acetylcholinesterase (AChE) enzyme. It is well established that symptoms of Alzheimer’s disease (AD) are related to low levels of ACh within the synaptic cleft, mainly in the cerebral cortex and hippocampus as determined by the post-mortem analysis of the brains of AD sufferers. One method for treating AD is the administration of AChE inhibitors, for instance, Galanthamine, a reversible AChE inhibitor is a FDA-approved drug for AD.
AChE activity has been reported as a marker for cholinergic neural activity. It has been demonstrated that the progressive reduction in cerebral AChE activity and is closely linked to the loss of neocortical cholinergic neurons is a characteristic of patients with AD.
[18F]fluorodeoxyglucose or FDG, the world’s most commonly prescribed fluorine-18 radiopharmaceutical is used to diagnose many forms of cancer and make early diagnosis of Alzheimer's disease through positron emission tomography (PET) imaging (see RHS image).
Object of the project Therefore, the imaging of AChE and its activity in the brain by PET represents a valuable tool for understanding of the AD progression. AChE inhibitors can be labeled with 18F or 125I as candidates for PET probes for the imaging of cerebral AChE. AChE substrates can also be synthesized and used as radioprobes not only for cerebral AChE imaging but also for measuring the effects of AChE inhibitors in an animal model.
Supervisors Associate Prof Alison Ung (UTS) Dr Tien Pham (ANSTO)
Campus UTS and ANSTO
Honours Projects for 2015
24
Title Development of ChipLC-ICP-MS
Description In this project, UTS and Agilent Technologies, the world’s leading vendor of analytical
instrumentation, will develop the world’s first hyphenated microfluidic chip liquid
chromatography–inductively coupled plasma–mass spectrometer (chipLC-ICP-MS) for the field
of metallomics.
Trace elements (<0.01%
of human body weight)
are critical in biological
processes. For example,
protein phosphorylation
cascades play a central
role in cell signaling and
development,
particularly in cancer
cells. Cyanocobalamin
(vitamin B12), which
forms two coenzymes
responsible for bio-
logical transformations,
contains cobalt. Iron in
haemoglobin binds
oxygen and carbon
dioxide, reactants and
products of cellular respiration. Copper and zinc are key components of superoxide dismutase,
an important enzyme in oxidation–reduction reactions. It is currently thought that around one-
third of all proteins in the human body contain at least one metal ion. These ions can act as
structural features or active sites for catalysis. Trace metals are so important to cell function that
cell chemistry must be characterised by the distribution of the metals and metalloids among
different biomolecules – defined as the ‘metallome’.
Hyphenated technologies such as liquid chromatography-inductively coupled plasma-mass
spectrometry (LC-ICP-MS) are the most effective way to detect trace elements in biological
samples. LC separates the sample fractions prior to detection by ICP-MS. ICP-MS has isotope
specificity, versatility (virtually any element can be detected), high sensitivity, and enormous
linear dynamic range (105–10
6) needed for efficient element detection. Figure 1 is one example
of the analysis of metallothionein isoforms by LC-ICP-MS. These isoforms are metal-binding
proteins associated with numerous disease states. Recent improvements in ICP-MS
instrumentation also detect non-metals such as phosphorous, expanding LC-ICP-MS analysis to
phosphorylated proteins.
Traditional standard (3 to 5 mm internal diameter) and narrow bore (1 to 2 mm internal
diameter) analytical LC columns are relatively easy to couple to ICP-MS due to compatible flow
rates. There are significant advantages in reducing the internal diameter of the separation column
including improved separation efficiencies, higher sensitivity and less solvent consumption.
However, reducing the internal diameter of the LC columns to micrometre-widths, also known
as nano-LC, presents new challenges. Hyphenation of nano-LC requires transport of eluents with
flow rates as low as 10 nL min-1
into the ICP-MS. This requires dedicated interfaces with sheath
flows to boost flow rates to levels capable of nebulisation; or employment of sheathless total-
consumption direct-injection nebulisers [8]. Further challengers include frequent blocking of the
capillary columns, requirements of sample pre-concentration prior to analysis with concentrator
columns and the minimisation of dead volumes to avoid band broadening leading to poor
separation efficiency.
All of these issues may be overcome by incorporation of the LC components into a
microfluidic lab-on-a-chip device.
The aim of this project is to design and fabricate an interface between a microfluidic liquid
chromatograph (chipLC) and ICP-MS.
Supervisors Philip Doble, David Bishop, Lucas Blanes
Contacts [email protected], Lucas Blanes( [email protected]), [email protected]
Figure 1: Separation metallothionein isoforms by LC-ICP-MS
Honours Projects for 2015
25
Title Developing new clinical diagnostic tests: Vitamin B12 in medications and
biological samples
Description Advances in medicine and the new focus on personalized treatments mean that there
will be increasing reliance on in vitro diagnostics and a requirement for simpler, rapid
techniques. This project aims to develop new analytical techniques which will be
applicable to drugs, metabolites and biomarkers using vitamin B12 as a model
compound.
Vitamin B12 has been chosen because of its clinical relevance in a number of disease
states such as pernicious anaemia and neurological disorders and as it is currently
measured using a time-consuming competitive binding luminescence assay which
requires removal of serum binding proteins before measurement. Other short comings
of this complex assay are interfering factors; in May 2012 there was a voluntary recall
of a cobalamin assay reagent (Siemens Healthcare Diagnostics, NY) due to inference
issues. Additionally, vitamin supplements are not tightly regulated either by the TGA
or the FDA. For example recent studies in the US of Vitamin D in OTC supplement
products have shown that they contained between 52 and 135% of the labelled levels
which has significant implications for patients being treated for deficiency. Levels of
Vitamin B12 in multivitamins are further complicated by the ability of other
components such as Vitamin C to interact with cobalamin so that it forms inactive
analogues. These factors make its analysis of interest.
Aptamers are short synthetic strands of DNA, RNA or amino acids with complex
three dimensional structures that bind unique protein or small molecule targets with
exquisite specificity. Aptamer technology is relatively new and has the capability to
distinguish between closely related isoforms. These molecules can be tagged with
lanthanides and rapidly detected by microwave plasma - atomic emission
spectroscopy (MP-AES).
In this project you will use aptamers to Vitamin B12 for the development of novel
analytical protocols for use with MP-AES. These protocols will be tested by analysing
levels of Vitamin B12 in over the counter multivitamin preparations and in biological
specimens. Results will be compared to those obtained by conventional techniques.
The project may be expanded to include other clinically relevant drugs and
metabolites such as antibiotics, lithium compounds, insulin, intrinsic factor etc.
Supervisor Prof. Philip Doble
Contact For further information please contact Philip Doble [email protected]
Honours Projects for 2015
26
Title Three dimensional multiplexed protein atlas of the mouse brain
Description The brain is the most complex organ in the human body. Animal models like the
laboratory mouse are commonly used to study diseases affecting the human brain.
Structural brain atlases are universal features of neuroscience laboratories. Atlases are
used to correlate features of disease with specific brain regions. Improving technology
has seen a move to functional brain atlases, where regional gene and protein expression
can be observed in conjunction with basic neuroanatomy via interactive software. This
project will develop the first interactive model of various proteins in the mouse brain
using advanced mass spectrometry techniques.
The aim of this project is to construct a standard three-dimensional atlas of metal -
transporter proteins in the C57BL/6 mouse brain using laser ablation-inductively
coupled plasma-mass spectrometry (LA-ICP-MS) and tagged antibodies.
Supervisor Philip Doble, David Bishop
Contact [email protected] or [email protected]
Honours Projects for 2015
27
Title Developing new applications for next generation elemental analysis
instrumentation
Description Agilent Technologies is the world’s leading vendor of analytical instrumentation and
leads the way in atomic spectroscopy and elemental analysis innovation. Its optical
spectroscopy headquarters is located in Melbourne and has been the site of multiple
new product developments in the past 2 years that have pushed back some of the long-
term barriers in atomic spectroscopy. Agilent’s Microwave Plasma – Atomic Emission
Spectroscopy (MP-AES) is a prime example of the continuing innovation around
instrumentation. The MP-AES is a world’s first product that provides excellent
performance without the need for expensive, difficult to obtain and often hazardous
bottled gases, thereby allowing it to be used remotely, at a mine site for example, or in
developing countries where access to bottled gases is difficult if not impossible.
There are a number of projects available to students with an interest in developing
novel applications for the MP-AES and Agilent’s next generation Inductively Coupled
Plasma – Optical Emission Spectroscopy (ICP-OES), instruments that are used in labs
around the world for accurate measurement of trace levels of a broad range of
elements. Think measurement of mercury in drinking water, trace levels of gold in
mine tailings, melamine adulteration of milk and infant formula and lead in toys.
In these projects you will research and develop novel analytical protocols for use with
the MP-AES and/or ICP-OES in the fields of food and agriculture and environmental
analysis. Results will be compared to those obtained by other analytical measurement
techniques and a range of international standards. The protocols and results developed
will be used to establish real world applications for use by researchers and analytical
chemists around the world.
Students working on these projects will have the opportunity to spend time at Agilent’s
state of the art Spectroscopy Technology Innovation Centre in Melbourne.
Examples of projects available (actual project to be determined by mutual agreement,
based on the interests of the student), include developing protocols to determine:
Trace elements in drinking water
Major and trace elements in infant formula
Minor nutrients in fertilizers
Heavy metals in toys
Toxic elements in green ink
Supervisor Philip Doble
Contact [email protected]
j
Honours Projects for 2015
28
Title
Projects at the National Measurement Institute (NMI) - multiple projects available.
Example: Improved analytical methods for the screening of Endogenous Anabolic
Androgenic Steroids
Description Background The ASDTL is the only laboratory in the Oceania region accredited by
the World Anti-Doping Agency (WADA) to carry out doping control analysis in
human sport and as such performs virtually all of the sports drug testing carried out in
Australia and New Zealand. ASDTL complies with the requirements of ISO/IEC
17025:2005 and is accredited by NATA. Drug testing is not just carried out at major
sporting events but is a year round activity with the analysis of some 8000 samples per
year from a range of amateur and professional sports. Our research program aims to
improve analytical techniques used in our laboratory and to investigate new forms of
doping which are currently undetectable. We receive funding from the WADA, the
Department of Health’s Anti-Doping Research Program and the US Partnership for
Clean Competition.
Project Recent research has demonstrated the improved effectiveness of the athlete
steroid biological passport when alternative steroid metabolites are included into
routine analytical procedures. However, their implementation into routine steroid
profiling is not trivial as their concentrations are generally quite low (less than 50
ng/mL) and stable isotopically labelled internal standards are not available. As such,
improved instrument capabilities are required for their successful analysis. This project
aims to implement the best identified alternative steroid metabolites into routine
screening at ASDTL and to investigate new instrumental technology available to
improve their analysis for their future potential implementation into the athlete steroid
biological passport.
Supervisor A number of supervisors at NMI are offering projects to UTS students.
Contact Email [email protected] for the full list of projects available.
Contact [email protected] for information about NMI and
individual projects.
Honours Projects for 2015
29
Titles 1. Creating improved electrodes for cochlear and vision implants. 2. Testing new tethered bilayer chemistries 3. Using tethered membranes to determine whether an ion channel prefers cations or anions. 4. Creating bacterial, mammalian and fungal tethered lipid bilayer models.
Description
1. Creating improved electrodes for cochlear and vision implants. This project aims to actually get cells to grow adjacent to gold electrodes using tethered bilayer lipid membranes. By investigating ways to grow cells directly onto gold we hope to demonstrate how to improve electrode design in cochlear and retinal implants. Student will learn to culture a cardio-myocyte cell line and to test their adhesion using fluorescence microscopy and impedance spectroscopy techniques.
Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)
2. Testing new tethered bilayer chemistries. In order to improve the function of tethered bilayers, unique tethering chemistries have been developed in cooperation our commercial partner SDx Tethered Membranes Pty Ltd. The electrode-tether binding properties of these chemistries will need to be tested in order to create new membrane models for antimicrobial research. Techniques the student will learn include impedance spectroscopy measures, surface chemistry and contact angle imaging. Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)
3. Using tethered membranes to determine whether an ion channel prefers cations or anions. This project uses bias voltages across a tethered bilayer lipid membrane to identify the preferred polarity of ion channel conductances. This project combines peptide ion channel research with physical chemistry. The student will learn advanced impedance spectroscopy techniques and physical chemistry interactions. The complexity of this project will suit students with good mathematical capabilities.
Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)
4. Creating bacterial, mammalian and fungal tethered lipid bilayer models. This project aims to create tethered bilayers using actual lipids from bacteria mammalian and fungal sources. These membranes can then be used to test new antimicrobial peptides. To ensure the validity of these membrane models, they will need to be tested using ablative mass spectroscopy techniques. As well as impedance spectroscopy, the student will receive training in Mass Spectrometry techniques from Dr Matt Padula.
Supervisor: Dr Charles Cranfield, Co-supervisors Dr Matt Padula and Prof Bruce Cornell (SDx Pty Ltd)
Contact [email protected]
A lipid membrane tethered to a gold electrode
Honours Projects for 2015
30
Title Novel nano-structured materials for high power energy storage
Description Greenhouse gas emissions from the consumption of fossil fuels are causing
disastrous climate change and global warming. The research and development of
electric vehicles to replace conventional vehicles has emerged as a solution to this
imminent problem. The progress of battery technology plays a key role in the
development of electric vehicles. This proposed project addresses the issues by the
development of innovative nano-structured materials for next generation batteries
with high capability, high power density and excellent retention. In this project, a
series of novel structured will be synthesised from wet-chemistry method. The
resultant nano-structured materials will be characterised by advanced instrumental
analyses such as scanning electron microscopy (SEM), transmission electron
microscopy (TEM), nitrogen adsorption, small angle X-ray diffraction (SAXRD),
and small-angle X-ray scattering (SAXS) to determine the micro-structure. Their
electrochemical performance will be investigated for high-power energy systems,
including lithium ion batteries, sodium ion batteries, lithium sulphur batteries and
lithium air batteries. In particular, in situ analyses (XRD & TEM) will be conducted
to investigate the working principle of energy storage systems. This project will
benefit UTS and Australia in the research forefront of nanotechnology, materials
engineering, energy storage and applied chemistry.
Experimental
techniques
Material synthesis, characterization and electrochemical measurement.
Equipment used Internal: Furnace, oven, microwave oven, glovebox , X-ray diffraction (in situ),
Scanning Electron Microscope, Atomic Force Microscopy, Transmission electron
Microscopy. (Faculty of Science)
External: Neutron & Synchrotron X-ray diffraction (in situ), Transmission electron
Microscopy. (ANSTO, Synchrotron Mel., USyd)
Supervisor Hao LIU
Contact [email protected]
Honours Projects for 2015
31
Title New phthalocyanine complexes as photodynamic therapy agents
Description
Photodynamic therapy (PDT) is a procedure used as a treatment for cancer. PDT
utilises compounds that can react with molecular oxygen to produce cytotoxic reactive
oxygen species when irradiated with light. The reactive oxygen species cause damage
to tumour cells and can lead to cell death.
Photosensitisers are typically strongly coloured compounds (to absorb plenty of light)
and so phthalocyanine compounds are an ideal choice.
An example of a metal-containing phthalocyanine (RuPc).
This project involves the synthesis of new phthalocyanine complexes that have
potential as PDT agents. To do this, ligands will be attached to the complex that enable
the complex be absorbed, distributed and eliminated from the body.
The synthetic methods will rely on organic techniques but will be coupled with
inorganic coordination chemistry. The project will utilise NMR spectroscopy together
with other techniques to characterize the new compounds.
Name of
supervisor(s)
Dr Andrew McDonagh
Contact [email protected]
Honours Projects for 2015
32
Title New Metal and Metal Oxide Core/Shell Nanoparticles
Description
In this project, nanoparticles containing metal oxide cores coated with gold will be investigated.
The particles will then be examined by ablating them with a laser and analysing the masses of
the ablated materials under various conditions.
Background: Nanoparticles made of gold have proven to be extremely valuable as probes to
visualise important, individual features within biological specimens. However, if multiple
targets are to be imaged, then a solid gold particle provides no means of distinguishing between
the targets. As a solution to this problem, core−shell structures may be used as extremely
sensitive bio-imaging probes if they possess an appropriate metal oxide core and gold shell.
Project outcomes: This project will result in new nanoparticles and new knowledge about the
laser ablation of the new particles under various conditions. The particles may be applied to
biological material to enable imaging of molecule/particle interactions as well as their
interaction with light.
Techniques Nanoparticle synthesis, molecular synthesis, measurement of optical properties, laser ablation,
mass spectrometry, scanning electron microscopy.
Name of supervisor(s) Dr Andrew McDonagh
Contact [email protected]
Honours Projects for 2015
33
Title Nitro-containing anti-cancer lipids
.
Description
Populations with high dietary intakes of omega-3 polyunsaturated fatty acids (ω-3
PUFAs) found in oily fish have lower incidents and fatalities from breast cancer. The
anticancer activity of ω-3 PUFAS have been further established in experimental and
animal models of breast cancer. The primary way in which PUFAs influence cancer
progression is through their metabolic conversion by enzymes in the body to
biologically active molecules.
Our research group (UTS and Prof. Michael Murray at the University of Sydney)
recently discovered an ω-3 PUFA metabolite with anticancer activity that we proposed
was responsible for the beneficial effects of ω-3 PUFA against breast cancer. Using
this metabolite as a starting point for a drug discovery program, we have developed a
novel class of anticancer drug (see figure) that kills breast cancer cells and shrinks
tumor size and volume in mouse models of breast cancer. We have found that electron
withdrawing groups, such as CF3, attached to the phenyl ring improves cancer killing
ability.
To produce more active molecules we would like to synthesise analogues bearing very
strongly electron withdrawing nitro groups, however we are unable to prepare these
compounds using our current synthetic methods. This project will explore new
methods to synthesie these compounds and prepare a small series of nitro-containing
analogues. The breast cancer cell killing ability of the new compounds will be assessed
by our partners at the University of Sydney.
OH
O
N N
O
H H
NO2
Supervisor Dr Tristan Rawling
Contact [email protected]
Honours Projects for 2015
34
Title Atomistic simulations on graphene-based materials for hydrogen storage and in
Li-ion batteries
Description
Graphene was experimentally fabricated for the first time in 2004 and was found with
excellent electrical, mechanical and thermal properties. Graphene has shown
promising applications as ultra-sensitive gas sensors, transparent electrodes in liquid
crystal display devices, large capacity electrodes in Li-ion batteries and hydrogen
storage materials. In this project, to further explore graphene applications in electronic
devices, especially in Li-ion batteries, and hydrogen storage materials, atomistic
simulation method (using Materials Studio software and other first principle
calculation softwares) is used to predict the electronic and magnetic properties of
graphene in the presence of substrates and different kinds of defects, the interaction
between hydrogen or Li-ion and graphene related materials, then to determine the
hydrogen storage behaviors or the performance of Li-ion batteries.
Hydrogen storage in 3D graphene structure
Supervisors Dr. Zhimin Ao and Prof. Guoxiu Wang
Contact [email protected]
Honours Projects for 2015
35
Title An investigation into ion suppression in quantitative tandem mass
spectrometry:
Project Description Tandem mass spectrometry coupled to high performance liquid chromato-
graphy (HPLC) has seen increasing use in bioanalysis in Pathology
laboratories worldwide in recent years. It has one “Achilles heel” however
and that is the occurrence of ion suppression.
Tandem mass spectrometers have an ion source where the eluent from the
HPLC is evaporated and the compounds of interest are charged, prior to
entering the mass spectrometer proper. During ionisation, the presence of
other co-eluting compounds has been shown to influence the ionisation of
the analyte/s, resulting in poor quantitation. One approach to this has been
the use of stable isotopes as internal standards, to normalise for ion
suppression. Stable isotopes frequently have to be prepared by custom
synthesis, making their cost prohibited, or in some cases they are unable to
be prepared in this manner at all. In other cases, even the use of stable
isotopes does not normalise for this phenomenon. Another approach is to
use more extensive sample preparation, but this adds cost and takes time,
extending turn-around times for assay results.
A better understanding of ion suppression and the factors that cause and/or
influence it may lead to approaches that expedite bioanalysis and
substantially reduce the cost. This project will address this issue.
Supervisors Dr Alison Beavis, UTS
Dr Ross Norris, Scientific Head, Pharmacology & Toxicology
St Vincent's Hospital
Contact [email protected]