a*star and king’s college london phd studentships october ... · 1.4 elucidating the molecular...
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A*STAR and King’s College London PhD Studentships
October 2019 Entry
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A*STAR and King’s College London PhD Studentships
When choosing a project from this catalogue in the funding section & research proposal section of the online application form, please enter the funding code that corresponds to the theme of your first project choice:
Molecules, Cells and the Basis of Disease: THEME1_2019
Neurosciences, Psychiatry and Mental Health: THEME2_2019
Psychological Medicine: THEME3_2019
Imaging and Biomedical Engineering: THEME4_2019
Physical Sciences: THEME5_2019
Informatics: THEME6_2019
Important dates:
Deadline for application Thursday 3rd January 2019 (midnight)
Application Outcome Early February
Interviews Tuesday 19th February
Interview Outcome Thursday 21st February
Acceptance of Offer Thursday 28th February
PhD Start Date October 2019
The 2019/20 studentships will commence in October 2019.
For further information or queries relating to the application process, please contact: [email protected]
Projects listed in this catalogue are subject to amendments, candidates invited to interview will have the opportunity to discuss
projects in further detail.
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Contents THEME 1: Molecules, Cells and the Basis for Disease _______________________________ 3
1.1 Role of alternative splicing in biology of neural progenitor cells ________________________ 4
2.1 Molecular mechanisms underpinning mucosal and systemic virulence in the fungal pathogen Candida albicans ________________________________________________________________ 6
3.1 Characterizing a new oncogenic pathway in bladder cance ____________________________ 8
4.1 The roles of genome architecture in cellular evolvability ______________________________ 9
5.1 Modelling neural crest anomalies using patient-derived human induced pluripotent stem cells (hiPSCs) and animal models ______________________________________________________ 11
6.1 How are human identical twins formed: characterising epigenomic variation contributing to monozygotic twinning ___________________________________________________________ 12
7.1 Identification of targets of nitric oxide / beta-catenin signalling, and the role of mechanosensitive miRNAs, in regulation of endothelial cell apoptosis. ____________________ 13
8.1 Genetic, cellular and pharmacologic correction of lipoid proteinosis ___________________ 14
9.1 The role of the skin microbiome in atopic dermatitis among Caucasians and Chinese ______ 15
10.1 Generating human dendritic cells from induced pluripotent stem cells for cancer immunotherapy _______________________________________________________________ 17
11.1 Defining novel nuclear functions for NESPRIN using BioID___________________________ 18
THEME 2: Neurosciences, Psychiatry and Mental Health ___________________________ 19
1.2 Transcriptional elongation mechanisms in neurodevelopmental disorders ______________ 20
THEME 3: Physiological Medicine _____________________________________________ 21
THEME 4: Imaging and Biomedical Engineering __________________________________ 22
1.4 Elucidating the molecular basis of thermogels as vitreous substitutes __________________ 23
2.4 Tackling Malaria Resistance: Engineering Anti-Malarial Nanostructures using Novel Anti-Microbial Macromolecules _______________________________________________________ 24
3.4 Artificial Intelligence Enabled Analysis of Post-Repair Tetralogy of Fallot ________________ 25
4.4 Artificial-intelligence powered PET reconstruction: Development and application to epilepsy 27
THEME 5: Physical Sciences __________________________________________________ 29
1.5 Understanding the Effectsof Conventional Solvents and Ionic Liquids on Chemical Reactivity UsingAdvanced Simulation Techniques _____________________________________________ 30
2.5 Does synergy between antimicrobial peptides enable them to overcome kinetic barriers and avoid triggering resistance? ______________________________________________________ 31
THEME 6: Informatics _______________________________________________________ 32
1.6 Deterministic vs Stochastic Spiking Neural Networks: Accuracy, Speed, and Robustness ____ 33
2.6 Quantifying and Visualizing “Self” through Lifelog Data Analytics ______________________ 34
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THEME 1: Molecules, Cells and the Basis for Disease
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1.1 Role of alternative splicing in biology of neural progenitor cells
First Supervisor: Dr Evgeniy Makeyev
School/Division & CAG: MRC Centre - Developmental Neurobiology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/eugene.makeyev.html
Second Supervisor: Dr Philipp Kaldis
A*STAR Research Institute: Institute of Molecular and Cell Biology (IMCB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imcb/Science/Scientific-Programmes/Scientific-Programmes-Profile/ResearchListID/3
Project Description:
The remarkable diversity of neurons in mammalian brain originates from specialized progenitor cells (NPCs) through a carefully controlled choice between continued proliferation and differentiation. The proposed PhD project will aim to understand how cell cycle-dependent changes in alternative splicing in general and alternative spicing of a key regulator of cell cycle, cyclin-dependent kinase 2 (CDK2) in particular affect biology of this important cell type. This will be achieved through bioinformatics analyses of single-cell RNA-sequencing data followed by experimental validation steps using RT-PCR, single-molecule RNA FISH, immunofluorescence (year 1-2); building targeting constructs and using them to modify the CDK2 gene in mouse (year 2-3); and in depth analyses of the splicing-specific CDK2 mouse models and delineating functional significance of a the most interesting subset cell cycle dependent splicing events using CRISP-Cas9 genome editing and various cell-based assays (year 3-4). These research objectives are based on exiting expertise of the Makeyev and Kaldis labs in bioinformatics, biochemistry, cell biology and mouse genetics, which will provide excellent training opportunities and will ensure successful completion of the project. We expect that this study will uncover novel molecular mechanisms regulating NPC proliferation and differentiation and will shed new light on CDK2 functions. This in turn will lead to better understanding of fundamental principles underlying normal development of the nervous system and may additionally provide biomedical insights relevant to diagnostics and treatment of neurodegenerative diseases and cancer.
Two representative publications from supervisors:
Yap K., Xiao Y., Friedman B.A., Je H.S., and Makeyev E.V. (2016) Polarizing the neuron through sustained co-expression of alternatively spliced isoforms. Cell Rep. 15, 1316-1328.
Windpassinger, C., Piard, J., Bonnard, C., Alfadhel, M., Lim, S., Bisteau, X., Blouin, S., Ali, N.A.B., Ng, A.Y.U., Lu, H., Tohari, S., Talib, S.Z.T., Van Hul, N., Caldez, M.J., Van Maldergem, L., Yigit, G., Kayserili, H., Youssef, S.A., Coppola, V., de Bruin, A., Tessarollo, L., Choi, H., Rupp, V., Rötzer, K., Roschger, P., Klaushofer, K., Altmüller, J., Roy, S., Venkatesh, B., Ganger, R., Grill, F., Chehida, F.B., Wollnik, B., Altunoglu, U., Al Kaissi, A., Reversade, B.*, and Kaldis, P.* (2017) CDK10 mutations in humans and
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mice cause severe growth retardation, spine malfomations and developmental delays. Am. J. Hum. Genet. 101, 391-403.
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2.1 Molecular mechanisms underpinning mucosal and systemic virulence in the fungal pathogen Candida albicans
First Supervisor: Professor Julian Naglik
School/Division & CAG: Mucosal & Salivary Biology Division
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/julian.naglik.html
Second Supervisor: Dr Yue Wang
A*STAR Research Institute: Institute of Molecular and Cell Biology (IMCB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imcb/Science/Investigators/Research-Directors/Research-Director-Profile/ResearchListID/78
Project Description:
Candida albicans (C. albicans) is a fungal pathogen that causes millions of mucosal infections and life-threatening disease in people with compromised immunity. C. albicans produces invasive filaments that attach and penetrate into mucosal tissue. These invasive filaments secrete candidalysin, a toxin which causes tissue damage and inflammation.
The production of invasive filaments by C. albicans is controlled by a protein called Hgc1. C. albicans unable to make Hgc1 do not produce tissue-invading filaments, but can still produce several factors that contribute to mucosal disease including candidalysin (encoded by ECE1) and adhesive proteins (encoded by ALS3 and HWP1) that enable the fungus to attach to host surfaces. This project will characterise the role of C. albicans filamentation, candidalysin, and these fungal adhesion proteins during infection.
To do this, we will use molecular biology and fungal genetics to create gene knockout mutants of these four proteins (Hgc1, candidalysin, Als3, Hwp1) individually and in combination. We will then infect human epithelial cells and mouse models to determine how important these fungal factors are in causing host damage and activating immune responses during different C. albicans infections. This will inform us of which fungal proteins are the most important factors in causing C. albicans disease.
Year 1: Construction of C. albicans gene knockout mutants.
Year 2: Characterisation of C. albicans mutants during infection of human epithelial cells.
Year 3: Characterisation of C. albicans mutants using mouse models.
Year 4: Thesis preparation, submission and PhD defence.
Two representative publications from supervisors:
Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G,
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Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B and Naglik JR (2016). Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature. 532, 64-68.
Zheng X, Wang Y and Wang Y (2004). Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis EMBO. 23, 1845-1856
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3.1 Characterizing a new oncogenic pathway in bladder cance
First Supervisor: Dr Claire Wells
School/Division & CAG: Comprehensive Cancer Centre
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/claire.wells.html
Second Supervisor: Dr Edward Manser
A*STAR Research Institute: Institute of Molecular and Cell Biology (IMCB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imcb/Science/Investigators/Senior-Pls/Senior-Pls-Profile/ResearchListID/4
Project Description:
Bladder cancer (BC) is a major cause of mortality worldwide, causing an estimated 150,000 deaths per year, new treatments are urgently required. During tumour invasion there is often a reduction in cell: cell junction proteins such as E-cadherin. In the Wells lab we found that another protein, PAK5 is enriched in the cell-cell junctions of BC cells and its depletion affects the formation of these junctions. PAK5 is a protein kinase (ie. potential drug target) but the substrates of Pak5 in cell-cell junctions are largely unexplored. Thus the function of PAK5 in junctions, and the role of PAK5 expression in cancer progression needs to be explored. The Manser Lab discovered that PAK5 has high basal activity (auto-activated) compared with the ubiquitous PAK4 which is also enriched in cell-cell junctions. This project brings together two labs with an interest in PAK5 to explore its role in bladder cancer.
Year 1: Wells lab - optimising in vitro/in vivo assays of cell migration using bladder cancer cells. Techniques: Migration Assay, Invadopodia assay, Zebrafish Dissemination Assay
Year 2: Manser lab - identifying new binding partners for PAK5 in the cell junctions. Techniques: CRISPR, BioID analysis
Year 3: Interaction studies in the Manser lab / return to KCL to perform cell based assays. Techniques Migration Assay, Invadopodia assay, Zebrafish Dissemination Assay, FRET:FLIM microscopy
Year 4: Continue cell based assays and clinical translation using human bladder cancer tissue samples. Techniques: Motility assays and Staining human tissue.
Two representative publications from supervisors:
Ahmad Fahim Ismail, Nouf Babteen, Tracey A. Martin , Wen G Jiang, Muhammad L Shamim Khan, Prokar Dasgupta and Claire M Wells (2017) PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells Biochem J. 2017
Tabanifar B, Zhao Z, Manser E PAK5 is auto-activated by a central domain that promotes kinase oligomerization. Biochem J. 2016 Jun 15;473(12):1777-89
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4.1 The roles of genome architecture in cellular evolvability
First Supervisor: Professor Snezhana Oliferenko
School/Division & CAG: Randall Division of Cell & Molecular Biophysics
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/snezhana.oliferenko.html
Second Supervisor: Dr Giulia Rancati
A*STAR Research Institute: Institute of Medical Biology (IMB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imb/Research/tid/2/Aneuploidy-and-Genome-Instability
Project Description:
Life on Earth is supported by networks of genes encoding RNA and protein products. How these networks evolve is intriguing and largely unresolved questions. Investigating cellular evolution helps elucidate network architecture and its rewiring during adaptation. This fundamental knowledge has important implications in our understanding of how cancer cells evolve. We recently showed that cells may evolve survival strategies to adapt to the loss of important genes, traditionally thought to be essential for viability. Such immediate response strategies likely differ depending on genome structure of the organism. Genes providing adaptive value may be amplified increasing their dosage, or mutated to affect the activity of their products, or their expression could be modulated through changes in their regulatory elements. We hypothesize that the repertoire of adaptive mutations available to cells during evolution depends on the genome architecture (e.g. chromosome number, transposon load, repetitive elements). We will test this hypothesis in a simple model eukaryote Schizosaccharomyces pombe. We will identify ‘evolvable’ genes and find genomic changes responsible for adaptation. We will classify them according to their genomic structure, position within a network and predicted functionality. By using genome editing, we will study how the immediate genomic context of the adaptive genes affects cellular evolutionary trajectories.
Y1. Identification of ‘evolvable’ genes in S. pombe (synthetic genetic arrays, yeast genetics).
Y2. Identification and analyses of genomic changes responsible for adaptive events (high-throughput whole-genome re-sequencing, bioinformatics).
Y3-Y4. In-depth mechanistic analyses of genomic context-dependent adaptation (molecular biology and genome editing, whole-genome re-sequencing, bioinformatics, advanced cellular imaging).
Two representative publications from supervisors:
Makarova, M., Gu, Y., Chen, J-S., Beckley, J., Gould, K. and S. Oliferenko. 2016. Temporal regulation of Lipin activity diverged to account for differences in mitotic programs. Current Biology. 26: 237-243.
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Liu G, Yong MYJ, Yurieva M, Srinivasan KG, Liu J, Lim JSY, Poidinger M, Wright GD, Zolezzi F, Choi H, Pavelka N and G. Rancati. 2015. Gene essentiality is a quantitative property linked to cellular evolvability. Cell. 163:1388-99.
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5.1 Modelling neural crest anomalies using patient-derived human induced pluripotent stem cells (hiPSCs) and animal models
First Supervisor: Dr Karen J Liu
School/Division & CAG: Centre for Craniofacial and Regenerative Biology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/karen.liu.html
Second Supervisor: Dr Boon Seng Soh
A*STAR Research Institute: Institute of Molecular and Cell Biology (IMCB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imcb/Science/Investigators/Independent-Fellows/Independent-Fellows-Profile/ResearchListID/80
Project Description:
Over the past few decades, our understanding of the developmental biology of the neural crest lineage has greatly improved. Therefore, we can now build a framework for sifting patient data and rapidly test promising candidate gene variants. The long-term goal will be to improve diagnosis and identify new candidate gene variants for targeted therapies.
Although many genes have been implicated in NC-linked pathologies or NC development (1466 entries in OMIM database), little is known about the specific role and relationships of these genes, in particular in NC formation in humans. Even for the most common disorders such as cleft lip/palate, the majority of cases have no known genetic association. The key difficulty is to definitively identify which gene variants are relevant and why their mutations are pathogenic. The overall focus of this project will be on a novel cranio-cardiac gene (CTNND1) identified in the Liu lab. The long-term goal will be to establish rapid assays to testnew candidate genes and to establish cellular models for therapies.
This project makes use of expertise in neural crest biology (Liu Lab, KCL) and neural and cardiac lineages (Soh Lab, A*STAR). The student will become expert in human genetics, human induced pluripotent stem cells, bioinformatics, stem cells, use of CRISPR/Cas9 approaches, animal models, molecular biology, biochemistry, cutting edge microscopy and image analysis.
Two representative publications from supervisors:
Gonzalez Malagon SG, Lopez Muñoz AM, Doro D, Bolger TG, Poon E, Tucker ER, Adel Al-Lami H, Krause M, Phiel CJ, Chesler L, Liu KJ.Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus. Nat Commun. 2018 Mar 19;9(1):1126.
Soh BS, Ng SY, Wu H, Buac K, Park JH, Lian X, Xu J, Foo KS, Felldin U, He X, Nichane M, Yang H, Bu L, Li RA, Lim B, Chien KR. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells. Nat Commun. 2016 Mar 8;7:10774.
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6.1 How are human identical twins formed: characterising epigenomic variation contributing to monozygotic twinning
First Supervisor: Dr Jordana Bell
School/Division & CAG: Twin Research & Genetic Epidemiology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/jordana.bell.html
Second Supervisor: Bruno Reversade
A*STAR Research Institute: Institute of Medical Biology (IMB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imb/Research/tid/12/Human-Genetics-Embryology
Project Description:
The study of twins has been invaluable in dissecting the genetic and environmental basis of human disease. However, very little is known about the factors that influence the process of twinning itself. This is particularly relevant for the case of human identical twins, or monozygotic (MZ) twins. A few families with a larger than expected number of MZ twins have been reported, which suggests that genetics may influence MZ twinning. The current proposal explores the role of biological processes that regulate the function of genes, or epigenetics, in MZ twins. Identifying an epigenetic signature that distinguishes identical twins, can help pinpoint factors that contribute to the twinning process. Understanding how twins are formed is a fundamental question in human biology.
The training undertaken by the student will include building a skillset in bioinformatics, computational genomics, statistical genetics, and molecular genetics. This will be complemented by transferrable skills in presenting and communicating the results to a broad audience of non-experts.
Two representative publications from supervisors:
Wahl S*, Drong A*, Lehne B*, Loh M*, Scott WR*, … 92 authors …, Bell JT*, Matullo G*, Gieger C*, Kooner JS*, Grallert H*, Chambers JC*. 2017. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature, 541(7635):81-86. *Joint first, and senior authors
Ho L, Tan SY, Wee S, Wu Y, Tan SJ, Ramakrishna NB, Chng SC, Nama S, Szczerbinska I, Chan YS, Avery S, Tsuneyoshi N, Ng HH, Gunaratne J, Dunn NR, Reversade B. ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway. Cell Stem Cell. 2015 Oct;17(4):435-47.
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7.1 Identification of targets of nitric oxide / beta-catenin signalling, and the role of mechanosensitive miRNAs, in regulation of endothelial cell apoptosis.
First Supervisor: Professor Albert Ferro
School/Division & CAG: School of Cardiovascular Medicine & Sciences
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/albert.ferro.html
Second Supervisor: Dr Frank Eisenhaber
A*STAR Research Institute: Bioinformatics Institute (BII)
Email: [email protected]
Website: http://www.bii.a-star.edu.sg/research/biography/franke.php
Project Description:
Apoptosis, or programmed cell death, is a physiological process by which damaged cells are removed from the body. However, in atherosclerosis (a disease characterised by progressive narrowing of arteries, and the principal cause of coronary heart disease and stroke), there is evidence that increased apoptosis of endothelial cells (the layer of cells lining all blood vessels in the body) is a key factor in progression of this disease. Increased apoptosis occurs especially at sites in the arterial tree where blood flow is disturbed, such as on curvatures and at branching points. It is precisely at such sites that atherosclerosis predominantly occurs.
We have identified a novel pathway within endothelial cells, involving the mediator nitric oxide (NO) and the signalling molecule β-catenin, that not only regulates apoptosis of endothelial cells but whose activity is critically dependent on flow; but the precise mechanism underlying this flow dependence is unclear. We hypothesise that it involves so-called micro RNAs (miRNAs, a type of RNA that can influence expression of certain genes), some of which are differentially produced under different flow conditions. This PhD will investigate the role of flow-sensitive miRNAs in regulation of NO / β-catenin-dependent apoptosis, and more generally the precise mechanisms underlying regulation of apoptosis by NO / β-catenin signalling.
The student will receive training both in cell-based research (at King’s College London) and in bioinformatics research (at A*STAR in Singapore). It is envisaged that years 1 and 4 will be spent in London, with years 2 and 3 in Singapore.
Two representative publications from supervisors:
The 160K Natural Organism Library, a unique resource for natural products research. Ng SB, Kanagasundaram Y, Fan H, Arumugam P, Eisenhaber B, Eisenhaber F. Nat Biotechnol. 2018 Jul 6;36(7):570-573. doi: 10.1038/nbt.418
Warboys CM, Chen N, Zhang Q, Shaifta Y, Vanderslott G, Passacquale G, Hu Y, Xu Q, Ward JP, Ferro A. Bidirectional cross-regulation between the endothelial nitric oxide synthase and β-catenin signalling pathways. Cardiovasc Res. 2014 Oct 1;104(1):116-26. doi: 10.1093/cvr/cvu173.
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8.1 Genetic, cellular and pharmacologic correction of lipoid proteinosis
First Supervisor: Professor John McGrath
School/Division & CAG: Basic and Medical Biosciences, St John’s Institute of Dermatology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/john.mcgrath.html
Second Supervisor: Professor Maurice van Steensel
A*STAR Research Institute: Skin Research Institute of Singapore (SRIS)
Email: [email protected]
Website: https://www.a-star.edu.sg/sris/Research/tid/30/van-STEENSEL-MauriceSkinType/L/SkinName/Admin?SkinSrc=/portals/34/skins/SRIS-AStar/Admin
Project Description:
This project is about a rare inherited (genetic) skin disease called lipoid proteinosis (LP). Affected individuals develop thickening and scarring of their skin. This project is about developing a better understanding of LP that may lead to better patient therapies. The starting point is that we know the gene for LP (called ECM1, encoding extracellular matrix protein 1) and we have characterised the causative mutations in several affected individuals and we have access to patient skin samples for culturing skin cells (keratinocytes and fibroblasts). The initial work for the student at KCL will be to culture cells (mainly fibroblasts) and define how these cells differ from control cells. The Singapore work plan will be to create animal models of the disease that reflect some of the characteristics of LP; the lab has success in establishing zebrafish models for other skin diseases. The student will establish assays of the LP phenotype for screening a library of chemical compounds (natural and synthetic) that might correct the phenotypic abnormality; additional compound library screening may also be undertaken at KCL depending on assays and outputs. Compounds that revert cellular abnormalities will then be assessed further in zebrafish to see whether they might could become future treatments for LP. Scarring is a key feature in LP and thus research on this disease may also have broader relevance to other conditions such as injury, wound healing and ageing.
Representative publication from supervisors:
Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). T. Hamada, W. H. I. McLean, M. Ramsay, G. H. S. Ashton, A. Nanda, T. Jenkins, I. Edelstein, A. P. South, O. Bleck, V. Wessagowit, R. Mallipeddi, G. E. Orchard, H. Wan, P. J. C. Dopping-Hepenstal, J. E. Mellerio, N. V. Whittock, C. S. Munro, M. A. M. van Steensel, P. M. Steijlen, J. Ni, L. Zhang, T. Hashimoto, R. A. J. Eady, J. A. McGrath. Human Molecular Genetics 2002; 11: 833-840.
This publication includes both supervisors and concerns the topic proposed for the studentship.
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9.1 The role of the skin microbiome in atopic dermatitis among Caucasians and Chinese
First Supervisor: Professor Carsten Flohr
School/Division & CAG: Basic and Medical Biosciences, St John’s Institute of Dermatology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/carsten.flohr.html
Second Supervisor: Dr John Common
A*STAR Research Institute: Skin Research Institute of Singapore (SRIS)
Email: [email protected]
Website: https://www.a-star.edu.sg/imb/Research/tid/26/Skin-Barrier
Project Description:
The skin microbiome represents an importantresearch area with much interest from the dermatological clinical and research communities, stemming from its role in many inflammatory skin diseases such as atopic dermatitis and psoriasis, seborrheic dermatitis, and acne. Despite this well-documented interest, the role of the skin microbiome as cause or consequence in inflammatory skin diseases faces substantial challenges due to a lack of foundational knowledge tracking host factors and the skin microbiome community members. Observing microbes that are documented to be beneficial or detrimental on the skin surface together with the associations with inflammatory profiles before and after treatment in atopic dermatitis patients will enable more predictive patient outcomes. The combination of studying both a Caucasian and an Asian population will allow the research team to identify the major microbial contributors to disease pathogenesis, which may differ between ethnic groups.This project will provide the opportunity to develop a wide skill set, including project design and management, requiring close working with the clinical teams in London and Singapore to collect samples for downstream analysis. The student will be required to extract DNA and prepare materials for metagenome sequencing and RNA sequencing. They will also have an opportunity to visit Dr Kezic’ group in Amsterdam to learn how to run cytokine assays from tape strips. Finally, the student will be required to develop the relevant skills to analyse large data sets with bioinformatics pipelines and statistical packages.
Two representative publications from supervisors:
Chng K.R., Tay A.S., Li C., Ng A.H., Wang J., Suri B.K., Matta S.A., McGovern N., Janela B., Wong X.F., Sio Y.Y., Au B.V., Wilm A., De Sessions P.F., Lim T.C., Tang M.B., Ginhoux F., Connolly J.E., Lane E.B., Chew F.T., Common J.E.*, Nagarajan N.*(2016) Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. Nature Microbiology, 568:219-53. doi: 10.1016/bs.mie.2015.09.030. *joint last author
Perkin MR, Craven J, Logan K, Strachan D, Marrs T, Radulovic S, Campbell LE, MacCallum SF, McLean WH, Lack G, Flohr C; Enquiring About Tolerance Study Team. Association between domestic water
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hardness, chlorine, and atopic dermatitis risk in early life: Apopulation-based cross-sectional study. J Allergy Clin Immunol. 2016 Aug;138(2):509-16.
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10.1 Generating human dendritic cells from induced pluripotent stem cells for cancer immunotherapy
First Supervisor: Dr Pierre Guermonprez
School/Division & CAG: Immunology, Infection & Inflammatory Disease
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/pierre.guermonprez.html
Second Supervisor: Dr Florent Ginhoux
A*STAR Research Institute: Singapore Immunology Network (SIgN)
Email: [email protected]
Website: https://www.a-star.edu.sg/sign/PEOPLE/Principal-Investigators/Investigator-Details?givenName=Florent&lastName=GINHOUX
Project Description:
Dendritic cells (DCs) are sentinel cells of the immune system. Understanding DCs biology is key for the development of anti-infectious vaccines and the implementation of innovative immunotherapies against cancer, including DCs-based cell therapy.
For all these reasons, it is essential to develop models of culture recapitulating the development of DCs. Here, we provide an integrated research approach tackling the differentiation process of DCs from stem cells that can potentially be generated for any patient.
This project combines tissue engineering, genome engineering and bioinformatics to understand the molecular processes controlling the acquisition and maintenance of DC identity through multiple developmental stages. In addition, we will explore the possibility to genetically inactivate in DCs, immune checkpoints limiting the development of anti-tumour immune responses.
Two representative publications from supervisors:
Mapping the human DC lineage through the integration of high-dimensional techniques. See P, Dutertre CA, Chen J, Günther P, McGovern N, Irac SE, Gunawan M, Beyer M, Händler K, Duan K, Sumatoh HRB, Ruffin N, Jouve M, Gea-Mallorquí E, Hennekam RCM, Lim T, Yip CC, Wen M, Malleret B, Low I, Shadan NB, Fen CFS, Tay A, Lum J, Zolezzi F, Larbi A, Poidinger M, Chan JKY, Chen Q, Rénia L, Haniffa M, Benaroch P, Schlitzer A, Schultze JL, Newell EW, Ginhoux F. Science. 2017 Jun 9;356(6342).
The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+Macrophages or Monocyte-Derived Dendritic Cells. Menezes S, Melandri D, Anselmi G, Perchet T, Loschko J, Dubrot J, Patel R, Gautier EL, Hugues S, Longhi MP, Henry JY, Quezada SA, Lauvau G, Lennon-Duménil AM, Gutiérrez-Martínez E, Bessis A, Gomez-Perdiguero E, Jacome-Galarza CE, Garner H, Geissmann F, Golub R, Nussenzweig MC, Guermonprez P. Immunity. 2016 Dec 20;45(6):1205-1218.
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11.1 Defining novel nuclear functions for NESPRIN using BioID
First Supervisor: Professor Cathy Shanahan
School/Division & CAG: School of Cardiovascular Medicine and Sciences
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/cathy.shanahan.html
Second Supervisor: Dr Brian Burke
A*STAR Research Institute: Institute of Medical Biology (IMB)
Email: [email protected]
Website: http://www.imb.a-star.edu.sg/
Project Description:
The nuclear envelope is a specialised part of the cell that when perturbed can promote a wide range of tissue specific diseases. The majority of these diseases affect muscle leading to muscle weakness and heart disease and they also show features of premature ageing. In this project we will seek to understand the function of a key protein present at the nuclear envelope called nesprin by identifying its binding partners. We will also determine how mutations in nesprins interfere with its binding to partner proteins and therefore lead to muscle disease. In the first year the student will make nesprin constructs that will be used to identify binding partners. In the second year these constructs will be used in a unique experimental system called BioID to identify binding partners at specific locations in the cell. In the 3rd and 4th years the functional significance of these interactions in muscle cell function and in ageing will be examined by depleting nesprins and its binding partners in cellular model systems of muscle differentiation and ageing. We will also use an animal model harbouring a nesprin mutation to determine how binding partner interactions are affected and how this impacts on heart and muscle function in vivo.
Two representative publications from supervisors:
A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations. Xie W, Chojnowski A, Boudier T, Lim JS, Ahmed S, Ser Z, Stewart C, Burke B. Curr Biol. 2016 Oct 10;26(19):2651-2658.
Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT, Wheeler MA, Ellis JA, Skepper JN, Vorgerd M, Schlotter-Weigel B, Weissberg PL, Roberts RG, Wehnert M, Shanahan CM. Hum Mol Genet. 2007 Dec 1;16(23):2816-33.
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THEME 2: Neurosciences, Psychiatry and Mental Health
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1.2 Transcriptional elongation mechanisms in neurodevelopmental disorders
First Supervisor: Professor Albert Basson
School/Division & CAG: Centre for Craniofacial and Regenerative Biology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/albert.basson.html
Second Supervisor: Dr Wee-Wei Tee
A*STAR Research Institute: Institute of Molecular and Cell Biology (IMCB)
Email: [email protected]
Website: https://www.a-star.edu.sg/imcb/Science/Scientific-Programmes/Scientific-Programmes-Profile/ResearchListID/20
Project Description:
Autism and associated neurodevelopmental disorders affect more than 1/100 individuals and represents a major burden to society and the health service. Recent human genetic studies have identified high confidence genetic risk factors for autism, allowing researchers to study the mechanisms that underlie these conditions. Understanding these mechanisms will allow us to find novel treatments for some of the debilitating features associated with these conditions. One of the potential mechanisms recently identified involves those required for the efficient expression of long genes. Many autism-associated genes appear to be longer than average, meaning that they may be particularly sensitive to disrupting the processes needed to express these genes. We have identified evidence that these mechanisms may be important for a specific subtype of autism caused by mutation of a specific gene called CHD8. The aims of this project will be to confirm that these mechanisms operate in cells that form brain cells and to determine the effects of disrupting these mechanisms in these cells. The project will employ a range of biochemical, cellular and next generation sequencing techniques. It is anticipated that the student will spend the first two years at KCL to identify specific mechanisms and establish techniques to study the development of brain cells and the last two years at A*STAR to determine the effects of disrupting these processes on the formation of brain cells and the expression of long, autism-associated genes.
Two representative publications from supervisors:
Suetterlin, P., Hurley, S., Mohan, C., Riegman, K.L.H., Pagani, M., Caruso, A., Ellegood, J., Galbusera, A., Crespo-Enriquez, I., Michetti, C., Yee, Y., Ellingford, R., Brock, O., Delogu, A., Francis-West, P., Lerch, J.P., Scattoni, M.L., Fernandes, C. & Basson, M.A. (2018). Altered neocortical gene expression, brain overgrowth and functional over-connectivity in Chd8 haploinsufficient mice. Cereb. Cortex. 28:2192-2206. https://doi.org/10.1093/cercor/bhy058
Tee WW, Shen SS, Oksuz O, Narendra V, Reinberg D. Erk1/2 Activity Promotes Chromatin Features and RNAPII Phosphorylation at Developmental Promoters in Mouse ESCs. Cell. Feb 2014;156(4):678-90.
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THEME 3: Physiological Medicine
There are no projects available within this theme for October 2019 Entry
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THEME 4: Imaging and Biomedical Engineering
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1.4 Elucidating the molecular basis of thermogels as vitreous substitutes
First Supervisor: Dr Cécile A. Dreiss
School/Division & CAG: Institute of Pharmaceutical Science
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/cecile.dreiss.html
Second Supervisor: Dr Xian Jun Loh
A*STAR Research Institute: Institute of Materials Research and Engineering (IMRE)
Email: [email protected]
Website: https://www.a-star.edu.sg/imre/Talent/ctl/StaffDetails/mid/16645/tid/206
Project Description:
We have developed a series of temperature-responsive hydrogels (thermogels) as vitreous substitutes (A*STAR). There have not been significant developments in the search for alternative vitreous substitutes with intraocular tamponade capabilities, outside the well-described materials comprising expansile gases and silicon oils, which have known limitations: gases cause great difficulties in patients post-operation, whereas silicon oils show long term biocompatibility issues. Thematerials we have developed have shown promising results innon-human primate models, however, an inflammatory response has been observed with variations in molecular weight and composition, which needs to be elucidated. In order to design and optimise materials which can be translated into the clinic, we need to characterise the morphology of the gels at the nanometer-scale andelucidate the molecular associations that are responsible for the functionality of the gels. This will be achieved by using state-of-the-art characterisation techniques, such as small-angle neutron scattering, performed at large-scale facilities, combined with mechanical measurements (KCL), in order to elucidate the molecular interactions and morphology which underlie the biological and in-vivo performance of the materials.
Overall, this project provides a very robust inter-disciplinary training for a PhD student, from the very fundamental (advanced physical characterisation techniques); material chemistry, with specialist polymersynthesis; all the way to the biological evaluation of the thermogels, with cell culture studies and testing in non-human primate models, with clear avenues towards developing these materials in the clinic
Two representative publications from supervisors:
E. A. Appel, X. J. Loh, S. T. Jones, C. A. Dreiss, O. A. Scherman, Biomaterials 2012, 33, 4646.
E. A. Appel, X. J. Loh, S. T. Jones, F. Biedermann, C. A. Dreiss, O. A. Scherman, Journal of the American Chemical Society 2012, 134, 11767.
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2.4 Tackling Malaria Resistance: Engineering Anti-Malarial Nanostructures using Novel Anti-Microbial Macromolecules
First Supervisors:
1A: Dr Bahijja Raimi-Abraham
1B: Professor Ben Forbes
School/Division & CAG: Institute of Pharmaceutical Science
E-mails: [email protected] / [email protected]
Websites: https://kclpure.kcl.ac.uk/portal/bahijja.raimi-abraham.html / https://kclpure.kcl.ac.uk/portal/ben.forbes.html
Second Supervisor: Dr Yi Yan Yang
A*STAR Research Institute: Institute of Bioengineering and Nanotechnology
Email: [email protected]
Website: http://www.ibn.a-star.edu.sg/research-areas-researcher.php
Project Description:
In 2018, the World Health Organisation (WHO) declared that “Resistance to antimalarial medicines is a threat to global efforts to control and eliminate malaria” highlighting the serious need to develop new therapeutic approaches with sustainable potency against the parasite. To successfully reduce the global threat of malarial resistance, aninterdisciplinary approach is required. This project uniquely combines an interdisciplinary approach to tackle malaria resistance. This project involves the development and synthesis of antimicrobial macromolecules which will be formulated into nanocarriers. These systems will then be tested in vitroand in vivofor their antimalarial activity.
Representative publications from supervisors:
Raimi-Abraham, B.T., Mahalingam, S., Davies, P.J., Edirisinghe, M., Craig, D.Q.M. Development and Characterization of Amorphous Nanofiber Drug Dispersions Prepared Using Pressurized Gyration (2015) Molecular Pharmaceutics,12 (11), pp. 3851-3861.
Bäckman P, Couet W, Forbes B, de Kruijf W, Arora S, Paudel A. Advances in experimental and mechanistic computational models to understand pulmonary exposure to inhaled drugs. Eur J Pharm Sci 113: 41-52 (2018)
W. Chin, G. Zhong, Q. Pu, C. Yang, W. Lou, P. F. De Sessions, B. Periaswamy, A. Lee, Z. C. Liang, X. Ding, S. Gao, C. Chu, S. Bianco, C. Bao, Y. W. Tong, W. Fan, M. Wu, J. L. Hedrick and Y. Y. Yang*, “A macromolecular therapeutic approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset”, Nature Communications 2018, 9, 917.
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3.4 Artificial Intelligence Enabled Analysis of Post-Repair Tetralogy of Fallot
First Supervisor: Professor Alistair Young1 (pp Professor Sebastien Ourselin HOS)
School/Division & CAG: School of Biomedical Engineering & Imaging Sciences
E-mail: [email protected] / [email protected]
Website: https://kclpure.kcl.ac.uk/portal/sebastien.ourselin.html
Second Supervisor: Dr Su Yi
A*STAR Research Institute: Institute of High Performance Computing
Email: [email protected]
Website: https://www.a-star.edu.sg/ihpc
Project Description:
Tetralogy of Fallot (TOF) is the commonest type of congenital heart disease, and there is now a large and growing population of adults with TOF. The surgical repairs these patients require early in life often lead to residual pulmonary regurgitation that can cause eventual right ventricular enlargement and dysfunction, and high rates of heart failure, arrhythmias, and sudden cardiac death. A critical decision is whether and when to perform pulmonary valve replacement to prevent worsening heart function. This project will develop new machine learning and artificial intelligence methods to characterise patients with TOF and determine new predictive biomarkers to aid this decision. During the course of this project the student will:
1. Learn state of the art machine learning algorithms and apply them to patient data (Year 1) 2. Develop biomechanical analyses using high performance computing resources in Singapore
(Years 2-3) 3. Determine the predictive power of new biomechanical indices in patients with and without
pulmonary valve replacement (Year 4).
This project will suit a student who wants to learn the latest medical imaging and bioengineering techniques and how new artificial intelligence methods can provide valuable clinical information critical for patient management.
Two representative publications from supervisors:
Gilbert K, Pontre B, Occleshaw C, Cowan BR, Suinesiaputra A, Young AA. 4D Modelling for Rapid Assessment of Biventricular Function in Congenital Heart Disease. (2017) Int J Cardiovasc Imaging. doi:10.1007/s10554-017-1236-6.
L. Zhong, L. Gobeawan, Y. Su, J. L. Tan, D. N. Ghista, T. Chua, R.S. Tan, and G.S. Kassab, Right ventricular regional wall curvedness and area strain in patients with repaired Tetralogy of Fallot, Am.
1 Professor Young joined King’s College London in October 2018 and the web-link to his research profile will be updated as soon as it is available.
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J. Physiol. Heart Circ. Physiol., 302(6): H1306-H1316, March 2012. DOI: 10.1152/ajpheart.00679.2011
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4.4 Artificial-intelligence powered PET reconstruction: Development and application to epilepsy
First Supervisor: Professor Alexander Hammers
School/Division & CAG: Imaging and Biomedical Engineering Clinical Academic Group
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/alexander.hammers.html
Second Supervisor: Dr Anthonin Reilhac
A*STAR Research Institute: Clinical Imaging Research Centre (CIRC)
Email: [email protected]
Website: https://www.circ.nus.edu.sg/
Project Description:
We propose to harness the latest developments in artificial intelligence (AI) for AI-powered PET image reconstruction for a quantum leap in image quality.
The essence of the new paradigm is to embed knowledge of image content, learned from databases of high quality synthetic images, directly into the PET image reconstruction. This reconstruction approach also provides a natural mechanism to map data sets from multiple centres and scanners to a common high quality image reference. While the ideas are generally applicable to any PET imaging protocols and areas of investigation, we focus here on [18F]FDG PET imaging for the identification of the epileptogenic zone in focal epilepsies. The student will first use real MR images to build a database of high quality numerical brain models including epileptogenic zones and will generate, via Monte Carlo simulation, the corresponding standard low-resolution, high-noise PET images.
Various AI models will then be tested within the tomographic reconstruction framework and trained using the database of synthetic images to map the standard PET images back to the high-resolution, noise-free reference images.
This novel reconstruction approach will then be tested in the real-world application of identifying and characterising the epileptogenic zone in view of epilepsy surgery.
The technique will be developed with and applied to a cohort of subjects with epilepsy (age ~9-50) and memory disorders (age ~50-80). These are being acquired at KCL (PI: AH; 65 datasets available, 100 planned) to compare clinical brain [18F]FDG PET-CT and PET-MR data, on the same machine as installed at CIRC.
Two representative publications from supervisors:
Development and validation of a rebinner with rigid motion correction for the Siemens PET-MR scanner: Application to a large cohort of [11C]-PIB scans. Reilhac A, Merida I, Irace Z, Stephenson M, Weekes A, Chen C, Totman J, Townsend DW, Fayad H, Costes N. J Nucl Med. 2018 Apr 13. pii: jnumed.117.206375. doi: 10.2967/jnumed.117.206375.
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Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR. Mérida I, Reilhac A, Redouté J, Heckemann RA, Costes N, Hammers A. Phys Med Biol. 2017 Apr 7;62(7):2834-2858. doi: 10.1088/1361-6560/aa5f
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THEME 5: Physical Sciences
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1.5 Understanding the Effectsof Conventional Solvents and Ionic Liquids on Chemical Reactivity UsingAdvanced Simulation Techniques
First Supervisor: Dr Edina Rosta
School/Division & CAG: Chemistry
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/edina.rosta.html
Second Supervisor: Dr Marco Klähn
A*STAR Research Institute: Institute of Chemical & Engineering Sciences (ICES)
Email: [email protected]
Website: https://www.a-star.edu.sg/ices/Research-Development/ICES-Researcher-Portfolio/Marco-Kl%C3%A4hn-Dr
Project Description:
Electron transfer (ET) between proteins is a vital for all living systems, and plays an essential role in photosynthesis and bioassimilation (the conversion of inorganic elements into biomass) as well as respiration (the use of biomass to generate energy). The first of these two processes, photosynthesis and bioassimilation supports life as we know it. Electron transfer is a central process for the transfer and storage of solar energy in materials. Our understanding of the corresponding biological electron transport can inspire new technological avenues for developing and advancing energy efficient technologies. However, robust, accurate, and predictive underlying theory and models are still missing for the structures, energetics and kinetics of ET processes in materials and biological systems. We aim to systematically study the properties of key parameters in ET to understand its effect on catalysis by studying a range of chemical reactions in various solvent environments, including ionic liquids (ILs). ILs are solvents whose properties can be adjusted through combining a large variety of different cations and anions. This allows to generate solvents with a wide range of physicochemical properties. For that reason ILs are also known as task-specific “designer solvents”. One of the main applications of ILs is their use as solvents for homogeneous catalysis including biocatalytic reactions. Important is to understand how the selection of ions effect chemical reactions and in this project this will be explored to find guidelines how such catalytic systems could be improved.
Two representative publications from supervisors:
On the Stability of Proteins Solvated in Imidazolium-Based Ionic Liquids Studied with Replica Exchange Molecular Dynamics. GS Lim, M Klähn*. The Journal of Physical Chemistry B, 2018, DOI:10.1021/acs.jpcb.8b06452
Structural characterization of arginine fingers: identification of an arginine finger for the pyrophosphatase dUTPases. GN Nagy, R Suardíaz, A Lopata, O Ozohanics, K Vékey, BR Brooks, ..., E Rosta*. Journal of the American Chemical Society 138 (45), 15035-15045, 2016
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2.5 Does synergy between antimicrobial peptides enable them to overcome kinetic barriers and avoid triggering resistance?
First Supervisor: Dr James Mason
School/Division & CAG: School of Cancer and Pharmaceutical Sciences
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/james.mason.html
Second Supervisor: Dr Peter Bond
A*STAR Research Institute: Bioinformatics Institute (BII)
Email: [email protected]
Website: http://www.bii.a-star.edu.sg/research/bmad/msmd.php
Project Description:
We are in the midst of a worldwide crisis due to the emergence of antibiotic resistant bacteria. A possible route to combatting this threat is to take inspiration from Nature; animal host defences consist of an arsenal of multiple antimicrobial peptides (AMPs), which may act synergistically with one another, and with a greater efficiency such that the bacteria are killed before resistance can emerge. In this project, we aim to explore this notion of antimicrobial synergy, based on a cutting edge and multidisciplinary approach encompassing the fields of microbiology, biophysics, and computational biology. We will determine how AMPs act in synergy against different bacterial pathogens, and how this relates to the risk of resistance. At King’s, in Year 1, the synergistic action of various AMPs will be characterized experimentally, and promising AMPs will be structurally determined. At A*STAR, in Years 2-3, the interaction of these AMPs with bacterial envelopes will be computationally modelled, to understand their molecular mechanisms of action. In the final year, upon returning to King’s, there will be an opportunity to experimentally explore and refine hypotheses generated from the computational studies in Singapore. Given the topic of antimicrobial resistance is one of acute global concern, the impact of this combined multidisciplinary approach can be expected to be substantial. As well as providing insights that may lead to new strategies for treating microbial infections, the skills learned during this project will provide ideal preparation for a future leader in academic research or the pharmaceutical industry.
Two representative publications from supervisors:
Kozlowska, J., Vermeer, L.S., Rogers, G.B., Rehnnuma, N., Amos, S-B.T.A., Koller, G., McArthur, M., Bruce, K.D. & Mason, A.J.*Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli. PLoS Pathogens2014(10) e1004104.
Huber,R.G., Berglund,N.A., Kargas,V., Marzinek,J.K., Holdbrook,D.A., Khalid,S., Piggot.T.J., Schmidtchen,A., Bond,P.J.*A thermodynamic funnel drives bacterial lipopolysaccharide transfer in the TLR4 Pathway. Structure2018(26) 1151-1161. (Cover Article).
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THEME 6: Informatics
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1.6 Deterministic vs Stochastic Spiking Neural Networks: Accuracy, Speed, and Robustness
First Supervisor: Professor Osvaldo Simeone
School/Division & CAG: Informatics
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/osvaldo.simeone.html
Second Supervisor: Dr Chua Yamsong
A*STAR Research Institute: Institute of Infocomms Research (I2R)
Email: [email protected]
Website: https://www.a-star.edu.sg/Research/Research-Focus/Infocomms
Project Description:
For all its recent breakthroughs, modern machine learning based on deep neural networks is becoming increasingly unaffordable in terms of computing and energy resources needed to run training algorithms that achieve state-of-the-art performance. This poses possibly insurmountable challenges for the implementation of efficient learning methods on resource-limited devices such as smart sensors or wearables. A possible solution to this problem is the adoption of the new paradigm of neuromorphic computing, which relies on energy-efficient sparse spike-domain processing and communication that are inspired by the operation of the brain. Whether Spiking Neural Networks (SNNs) can overcome the limitations of conventional deep networks for the implementation of low-power machine learning is a fundamental question that is currently being investigated by major technology companies and universities. In this project, this issue will be tackled both theoretically and through hands-on experiments by leveraging the complementary expertise of the respective research teams at KCL and A*STAR. Specifically, this research will seek to understand whether conventional deterministic models for SNNs can be improved by probabilistic models, which are typically used in neuroscience to model the brain operation, in terms of accuracy, speed, and robustness. Inthe first two years, at KCL, the project will concentrate on deriving models and learning rules for probabilistic SNNs. In the last two years, at A*STAR, the research will shift to aspects related to implementation, with a focus on the comparison between deterministic and probabilistic SNNs and on the use of nano-scale devices for the implementation of probabilistic SNNs.
Two representative publications from supervisors:
A. Bagheri, O. Simeone, and B. Rajendran, “Training Probabilistic Spiking Neural Networks With First-to-Spike Decoding.” in Proc. IEEE International Conference on Acoustics, Speech, and Signal Processing, Apr. 2018.
J. Wu, Y. Chua, and H. Li, (2018), “A Biologically Plausible Speech Recognition Framework Based on Spiking Neural Networks.”, In Neural Networks (IJCNN), 2018 International Joint Conference
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2.6 Quantifying and Visualizing “Self” through Lifelog Data Analytics
First Supervisor: Dr Rita Borgo
School/Division & CAG: Informatics
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/rita.borgo.html
Second Supervisor: Dr Lim Joo Hwee
A*STAR Research Institute: Institute for Infocomm Research (I2R)
Email: [email protected]
Website: https://www.a-star.edu.sg/i2r
Project Description:
In the past decades, personal mobile/wearable devices have become prevalent and a huge amount of personal lifelog data (importantly photos) is collected. Such data need not be kept only as a digital “backup” of the self; rather they provide immense opportunities for personal health management and entertainment. However, extracting useful information from the lifelog data is not trivial considering the huge volume and inconsistencies of the data. It is also not trivial to convey such information in a format that can be effectively consumed by the user and empower him/her to become active actor in the management of his/her own wellbeing. To achieve this purpose this project will explore the analytics of lifelog data to support personal health management. Combining findings in neuropsychology, and developments in artificial intelligence and human-computer interaction, this project aims to build a cognitive theory-based computational framework for lifelog analytics. The candidate will contribute in exploring thisdirection through the development of neural-inspired deep learning algorithms, interactive virtual reality/augmented reality systems, and the validation of research hypotheses through the design of experiments. Candidates should have a background in Computer Science or related fields, with a strong interest in artificial intelligence, human-computer interaction, and/or design research. You will have demonstrable experience of machine learning, programming 2D/3D interactive systems. Demonstrable knowledge of the main 3D Engines (e.g., Unity and Unreal) is preferred. Knowledge of psychology and neural science will be an advantage but is not required. You will also have an excellent knowledge of both written and spoken English. Candidates will be trained jointly be KCL (https://www.kcl.ac.uk/study/doctoral-studies/index.aspx) and A*STAR (https://www.a-star.edu.sg/), with 4 year’s candidature split between to places. In Year 1, the student is in KCL for course work and preliminary training on the research topic, including literature survey. Through Year 2 to Year 3, year, the candidate will stay in A*STAR (SG) to conduct research (with supervision from experts) in computational methods for lifelog visual summarization, and develop interactive system for lifelog visualization for cognitive intervention, preferably to elder adults. There will be a 2-3 month interim visit to KCL in each year. In Year 4, the student will finish the experiment evaluation including user studies and refine the system and methods where applicable.
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Two representative publications from supervisors:
J. Walker, R. Borgo,M. W. Jones. TimeNotes: A Study on Effective Chart Visualization and Interaction Techniques for Time-Series Data, IEEE Transactions on Visualization and Computer Graphics, vol. 22, no. 4, pp. 549-558, 2016
Q. Xu, V. Subbaraju, A.G. Molino, J. Lin, F. Fang, J.H. Lim. Visualizing Personal Lifelog Data for Deeper Insights at the NTCIR-13 Lifelog-2 Task. NTCIR-13 2017.