Summer research scholarship projects

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Summer Research Scholarship Program Genomics and Computational Biology Hamilton group Project Titles: Methods in bio-­‐image analysis and classification Modelling biological systems Project Description: Biological imaging is undergoing rapid growth and development in microscope technology. High-­‐throughput screens for drug and genomic discovery are leading to massive image sets in need of new methods of quantification, modelling, analysis, classification, feature extraction, organisation, visualisation, comparison, hypothesis testing and inference. The core of the group’s research is to develop the methodologies, algorithms and tools to maximise the benefit of the new data sources becoming available. The group collaborates closely with cell biology, bioinformatics and mathematics groups in creating these methodologies and utilises and develops techniques in areas such as machine learning, data clustering, graph algorithms, image segmentation, statistical testing and mathematical modelling. Project duration: 10 weeks Primary Supervisor: Dr Nick Hamilton Further info: Please contact Dr Nick Hamilton on n.hamilton@imb.uq.edu.au


Ragan group We use advanced computing and bioinformatics to make quantitative inferences inferences about how genomes, gene families, protein families and biomolecular networks evolve, diversify and function in mammalian cells and in bacteria. Project Title: Gene exchange and genetic recombination in pathogenic bacteria, particularly multidrug-­‐resistant Staphylococcus aureus Description: Application of bioinformatic and computational methods including multiple sequence alignment, phylogenetic inference and topology comparison to detect instances of lateral genetic transfer among hundreds of S. aureus genomes, and correlation with genetic determinants of infectivity, multidrug resistance and virulence. Expected outcomes and deliverables: Experience with important methods in bioinformatics and molecular phylogenetics / phylogenomics including automated workflows, multiple sequence alignment, tree inference and comparison, computing and data management. Suitable for: Year 3-­‐4 students with interest in bioinformatics, molecular phylogenetics and/or computational analysis of infectious disease microorganisms, with solid fundamentals in Unix/Linux, a modern scripting language (preferably Python) and R. Primary Supervisor: Dr Cheong Xin Chan Further info: Interested students please contact Dr Cheong Xin Chan c.chan@imb.uq.edu.au and/or Professor Mark Ragan m.ragan@imb.uq.edu.au Project Title: Networks of gene exchange across entire microbial ecosystems Description: Application of advanced statistical, informatic and computational approaches to model the transfer of genetic material across the microbial biosphere. Expected outcomes and deliverables: Experience with bioinformatic and computational workflows, non-­‐standard methods based on k-­‐mer frequency spectra, and D2 statistics; new insights into the world of microbial genomes. Suitable for: Masters-­‐level or adventurous Year 3-­‐4 students with strong grounding in frequentist statistics and scripting (preferably Python), and familiarity with Unix/Linux. Primary Supervisor: Dr Leanne Haggerty


Further info: Interested students please contact Dr Leanne Haggerty and/or Professor Mark Ragan m.ragan@imb.uq.eu.au Project Title: Genes for adaptation to extreme environments in algal genomes Description: Application of bioinformatic and computational methods including sequence clustering, multiple sequence alignment, phylogenetic inference and statistical analyses to understand genomic adaptation to temperature and/or environmental stress. For some datasets, also structural and functional annotation. Expected outcomes and deliverables: Experience with important methods in bioinformatics, evolutionary biology and molecular phylogenetics including data management, automated workflows and computing. Suitable for: Year 3-­‐4 students with interest in bioinformatics, molecular evolution and/or molecular phylogenetics / phylogenomics particularly of marine organisms, with solid fundamentals in Unix/Linux, a modern scripting language (preferably Python) and R. Primary supervisor: Dr Cheong Xin Chan Further info: Interested students please contact Dr Cheong Xin Chan c.chan@imb.uq.edu.au and/or Professor Mark Ragan m.ragan@imb.uq.edu.au Project Title: Genes for brain development, social behaviour and cognition in the Neandertal genome Description: Exploratory project examining adaptive genetic selection of genes potentially involved in brain development, social behaviour and/or cognition in the published Neandertal and Denisovan genomes. Expected outcomes and deliverables: Experience with important methods in bioinformatics and evolutionary biology; understanding of brain and related gene systems in human evolution. Suitable for: Year 3-­‐4 or Masters students able to work semi-­‐independently in a supportive research environment. Must be familiar with Unix/Linux and a modern scripting language (preferably Python); experience with the UCSC Genome Browser, Java, Matlab and/or R would be beneficial. Primary supervisor: Professor Mark Ragan Further info: Interested students please contact Professor Mark Ragan m.ragan@imb.uq.edu.au


Project Title: Networks of molecular interactions and genetic regulation in cancer Description: Application of methods from bioinformatics, knowledge engineering and/or machine learning to infer and analyse networks of biomolecular interaction based on large gene-­‐expression and other datasets in breast, pancreatic, prostate and other cancers. Expected outcome and deliverables: Experience with important methods in bioinformatics and computational biology as applied to mechanistic understanding of cancer, including cancer subtypes and metastasis. Experience with computational workflows, data management and specialised methods e.g. ontologies, knowledge engineering, or machine learning. Suitable for: Year 3-­‐4 or Masters students with interest in cancer or other complex disease, and strong grounding in statistics. Familiarity with either bio-­‐ ontologies, or machine learning techniques (e.g. SVMs, random forests), is strongly recommended. Primary supervisor: Dr Melissa Davis (knowledge engineering) and/or Dr Sriganesh Srihari (machine learning). Further info: Interested students please contact Professor Mark Ragan for initial discussion m.ragan@imb.uq.edu.au , then either Dr Melissa Davis m.davis@imb.uq.edu.au or Dr Sriganesh Srihari s.maniganahallisrihari@imb.uq.edu.au


Molecular Genetics and Development Little group Project Title: Mechanism regulating tubular formation in a 3D culture system Project duration: 8 weeks Description: Kidney-­‐derived stromal cells can form tubular structures in 3D culture and this project is to Investigate the potential signalling pathways involved in this process. Expected outcomes and deliverables: For example, scholars may gain skills in data collection, or have an opportunity to generate publications from their research. Students may also be asked to produce a report or oral presentation at the end of their project. Suitable for: This project will involve 3D cell culture, immunofluorescence and possibly confocal microscopy and images processing. It is suitable for 3rd or 4th year student. Primary Supervisor: Dr Joan Li Further info: Please contact Dr Joan Li if you would like further information joan.li@imb.uq.edu.au


Hogan group Project Title: Characterization of a novel transgenic reporter for snail2 expression Project Description: In the Hogan lab we study the formation of the vertebrate vascular network, consisting of both blood and lymphatic vessels, using the zebrafish as a model organism. New vessels form largely via sprouting of vessels from pre-­‐existing vasculature, which is termed angiogenesis for blood vessels and lymphangiogenesis in the case of lymphatic vessels. In zebrafish embryos angiogenic sprouting of arterial vessel initiates at approximately 22 hours post fertilization (hpf), followed by sprouting of venous vessels that will later comprise the lymphatic system. While zebrafish embryos are highly transparent, these processes can be imaged live. Recently, we have established a novel transgenic line in the lab that functions as a reporter for snail2 transcription. Snail2 is a well-­‐established transcription factor that functions as an inducer of a process referred to as epithelial-­‐to-­‐ mesenchymal transition (EMT). We would like to use the transgenic zebrafish embryos to visualize which endothelial cells undergo EMT during sprouting angiogenesis. Expression analysis will include live confocal microscopy, antibody stainings and in situ hybridization experiments. Project duration: 10 weeks Primary Supervisor: Dr Anne Lagendijk Further info: Please contact Dr Anne Lagendijk if you would like further information a.lagendijk@uq.edu.au Project Title: The influence of blood flow on endothelial morphogenesis Project Description: With this project we would like to perform a detailed analysis of the morphogenetic events prior and after the onset of blood flow. We will make use of a great variety of transgenic lines available in the lab that will differentiate between components of the blood vasculature like arteries, veins and lymphatics. We will perform transient knock-­‐down approaches to eliminate blood flow during development and also study zebrafish mutants which lack blood flow. Project duration: 8-­‐10 weeks Primary Supervisor: Dr Anne Lagendijk Further info: Please contact Dr Anne Lagendijk if you would like further information a.lagendijk@uq.edu.au


Molecular Cell Biology Parton group Our research focuses on the cell surface in health and disease, specifically the organisation, dynamics, and functions of the plasma membrane. We use electron microscopy, live confocal microscopy, molecular biology, and biochemistry to examine membrane dynamics and microdomain organisation, in particular the function of caveolae. These domains are involved in signal transduction and lipid regulation and have been linked to disease states such as muscular dystrophy and cancer. We use a range of model systems including cultured cells, the zebrafish and mouse. Project Title: Membrane dynamics in zebrafish models of muscular dystrophies. Project duration: 8-­‐10 weeks Description: We are interested specifically in the role of the Junctophilin gene in the development of the early muscle membrane systems. We believe that perturbation of junctophilin expression results in compromised muscle development and function. The optically transparent zebrafish provides an ideal model to test this hypothesis, using gene-­‐knockdown, expression analysis by insitu hybridisation, and live imaging of fluorescent transgenic lines using confocal microscopy. Expected outcomes and deliverables: Students will be given training in expression analysis and the use of zebrafish as a model system. This project has the potential to be developed into a larger, more in-­‐depth study down the track Suitable for: This project would be suitable for third year students looking for experience and training before considering honours and/or a PhD. Primary Supervisor: Dr Thomas Hall Further info: Please contact Dr Thomas Hall on t.hall5@uq.edu.au


Teasdale group Project Title: Defining host-­‐pathogen interactions during Salmonella infection Project duration: 10 weeks Description: This project will investigate the molecular details of various pathways and how they are modulated in response to infection with Salmonella, a leading cause of human gastroenteritis. Primary Supervisor: Dr Rohan Teasdale Further info: Please contact Dr Rohan Teasdale on r.teasdale@imb.uq.edu.au Project Title: Defining how Chlamydia manipulates the hosts membrane trafficking pathways during infections Project duration: 10 weeks Description: This project will investigate the molecular details of various membrane trafficking pathways and there contribution to the formation of the inclusion generated during infection with Chalmydia, the most common bacterial sexually transmitted disease. Primary Supervisor: Dr Rohan Teasdale Further info: Please contact Dr Rohan Teasdale on r.teasdale@imb.uq.edu.au Project Title: Characterisation of the mammalian endosomal protein complex called the retromer Project duration: 10 weeks Description: Retromer is a central regulator of early endosome protein trafficking that has recently been implicated in the progressive neurological disorders such as Alzheimer’s and Parkinson’s diseases. This project will examine the known cellular biochemical properties of retromer to determine the molecular mechanisms underlying these disease states. Primary Supervisor: Dr Rohan Teasdale Further info: Please contact Dr Rohan Teasdale on r.teasdale@imb.uq.edu.au


Yap group Project Title: Characterization of biomechanical properties of epithelial cells grown on stretchable substrates Project duration: 10 weeks Description: This project will investigate how mechanical forces contribute to the biology of cadherin based cell-­‐cell junctions. By using cells grown on stretchable substrates combined with high resolution imaging and fluorescence energy resonance transfer measurements, this interdisciplinary project study how cadherin receptors sense force and, transduce mechanical stress into biochemical signals. The results of this project will shed light on the role of cellular forces on in tissue organisation and how its (dys)regulation can derive in disease, such as cancer. Primary Supervisor: Dr Guillermo Gomez Further info: Please contact Dr Guillermo Gomez on g.gomez@imb.uq.edu.au


Schroder group Project Title: Construction of plasmids for the expression of inflammasome reporter genes Project duration: 10 weeks Description: The immune system is critical to defence against infection, but also drives unhealthy processes in disease. An important emerging player in innate immunity in both of these settings is the ‘inflammasome’ pathway. Inflammasomes are molecular machines that trigger immune system activation in response to infection or tissue damage. Inflammasomes enable immune defences to fight infection, but also drive unhealthy inflammation in a wide variety of human diseases, including hereditary fever syndromes, gout, diabetes, arthritis, asbestosis and Alzheimer’s disease. Pathway antagonists already show great clinical promise for the treatment of these debilitating diseases. The NLRC4 inflammasome mediates host defence against Gram-­‐negative pathogenic bacteria such as Salmonella, however the cellular mechanisms enabling this critical immune response are unclear. This project addresses this important knowledge gap, by cloning constructs encoding fluorescently tagged inflammasome components to enable imaging of inflammasome pathway activation in real time. Insight into such mechanisms of host defence may enable the future design of anti-­‐infective or anti-­‐inflammatory drugs. Primary Supervisor: Dr Kate Schroder Further info: Please contact Dr Kate Schroder on k.schroder@imb.uq.edu.au


Chemistry and Structural Biology Alewood group Project Title: Conotoxins that target chronic pain receptors Project duration: 10 weeks Description: Conotoxins are small bioactive highly structured peptides from the venom of marine cone snails (genus Conus). Over the past 50 million years these molluscs have developed a complex venom cocktail for each species with each venom comprised of 1000-­‐10000 distinct cysteine-­‐rich peptides for prey capture and defence. This project will focus on smaller conotoxins which were isolated from our transcriptome / proteome program and contain 2 or 3 disulfide bridges. In this project we will chemically synthesise two of these conotoxins and characterize them in vitro against a panel of ion channel receptors. Expected outcomes and deliverables: Applicants will gain skills in learning to use hplc chromatography, mass spectrometry, transcriptomics /proteomics analysis and solid phase peptide synthesis. This work will underpin future publications in this field. Students will also learn how to present their work in Group Meetings using Powerpoint presentations. Suitable for: This project is open to applications from students with a background in chemistry or biochemistry preferably in their 3rd or 4th year. Primary Supervisor: Professor Paul Alewood Further info: Please contact Paul Alewood beforehand at p.alewood@imb.uq.edu.au Project Title: Bioactive molecules, chemical protein synthesis and proteomics Project duration: 10 weeks Description: The research interests of our group include the discovery and total synthesis of peptide toxins from Australia’s venomous creatures, the chemical synthesis of proteins and bioactive peptides, development of new synthetic and analytical methods, heterocyclic chemistry, proteomics and bio-­‐organic and medicinal chemistry. Special emphasis is placed on determining the structure-­‐ function relationships of natural and/or designed molecules. Expected outcomes and deliverables: Applicants will gain skills in learning to use hplc chromatography, mass spectrometry, transcriptomics /proteomics


analysis and solid phase peptide synthesis. This work will underpin future publications in this field. Students will also learn how to present their work in Group Meetings using Powerpoint presentations. Suitable for: This project is open to applications from students with a background in chemistry or biochemistry preferably in their 3rd or 4th year. Primary Supervisor: Professor Paul Alewood Further info: Please contact Paul Alewood beforehand at p.alewood@imb.uq.edu.au


Cooper group Further information can be found at the Cooper Group website: http://cooper.imb.uq.edu.au Project title: Anti-­‐inflammatory small molecules for Alzheimers and Parkinsons Project duration: 8-­‐10 weeks Description: Interleukin 1β is a key component of the innate immune response vital for host protection against invading pathogens and aiding in cellular and tissue repair. However, IL-­‐1β is also a potent pyrogen and dysregulation leads to a wide variety of diseases including auto inflammatory disorders. We are developing a series of compounds which modulate IL-­‐1β through targeting the NLRP3 inflammasome signalling cascade. This project will involve synthesis of novel members of this compound series for testing against our lead compound with the aim to generate molecules with activity in disorders of the CNS (multiple sclerosis, Alzheimers and Parkinsons disease). Expected outcomes and deliverables: This project is oriented in the field of medicinal chemistry and will develop the synthetic and analytical skills of the successful applicant. The student will generate a number of small molecules using solution phase chemistry contributing to our series for future patent and/or publication. This project works across many disciplinary areas and molecules generated will be tested. The student can expect to complete the work with a good understanding of the underlying biology and the structure activity/property relationships within the series they are working. Suitable for: This project is open to applications from students with a background in chemistry, 3-­‐4 year students. Primary Supervisor: Dr Avril Robertson. Co-­‐supervisor: Professor Matthew Cooper Further Info: For further information please contact the Cooper group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application. Project title: Lipopeptide antibiotics to treat multidrug resistant bacterial infections Project duration: 8-­‐10 weeks Description: There is an urgent medical need for new antibiotics to treat infections caused by multidrug-­‐resistant (MDR) Gram-­‐negative pathogens, which is exacerbated by the paucity of drug candidates in the pharmaceutical


pipeline. Based on our established methods, this project will use solid phase synthesis to make naturally occurring and novel octapeptin derivatives for testing using an in-­‐house collection of drug resistant bacterial strains as well as NDM-­‐1 producing Gram-­‐negative bacteria. Expected outcomes and deliverables: The successful applicant will generate a number of small molecules using solid phase chemistry in order to complete our set of molecules for publication. Molecules generated will be tested against a panel of bacteria but will also be tested for antifungal activity giving likelihood of 2 publications. The motivated student can expect to complete the work with a good understanding of the underlying biology and the structure activity/property relationships within the series they are working. This project is oriented in the field of medicinal chemistry and will develop the synthetic and analytical skills of the successful applicant. Suitable for: This project is open to applications from students with a background in chemistry, 3-­‐4 year students. Primary Supervisor: Dr Avril Robertson. Co-­‐supervisor: Professor Matthew Cooper Further Info: For further information please contact the Cooper group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application. Project Title: Natural product anti-­‐infective drug discovery Project duration: 8-­‐10 weeks Description: Natural products have been a valuable source of new drugs leads for hundreds of years. We have initiated a research collaboration to screen plants from South East Queensland, which is home to a large diversity of species, for anti-­‐infective activity. We will also undertake chemotaxonomy analyses of selected plant species using LC-­‐MS. Expected outcomes and deliverables: This project aims to identify new anti-­‐ infective active compounds from plants, as well as helping to resolve plant taxonomy issues using a chemotaxonomy approach. This project will enable the student to get hands on experience with analytical chemistry equipment and techniques, as well as undertake preparative scale compound isolation and structure elucidation with NMR and MS. Suitable for: This project is open to applications from students with a background in chemistry, 2-­‐4 year students. This project will suit students who are interested in natural products chemistry, analytical chemistry and/or anti-­‐ infective drug discovery.


Primary Supervisor: Dr Mark Butler. Co-­‐supervisor: Prof Matt Cooper Further info: For further information please contact the Cooper Group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application. Project Title: Tackling Gram-­‐Negative Bacterial Infections One Residue at a Time Project duration: 8-­‐10 weeks Description: The polymyxin (PMB) class of antibiotics (Polymyxin B and colistin), identified in 1947 as secondary metabolite nonribosomal peptides produced by the soil bacterium Bacillus polymyxa, are the last-­‐resort therapeutic option to treat Gram-­‐negative infections that fail to respond to all other currently available treatments. The polymyxins are cyclic hepapeptides highly decorated with diaminobutyric acid (Dab) residues that are important for the biological activity and solution-­‐state NMR has revealed that PMBs exhibit a conformational preference toward a type II’ b-­‐turn. This project will involve the solution-­‐phase synthesis of Fmoc-­‐protected amino acid peptidomimetics and their incorporation into PMB via solid phase peptide synthesis. Expected outcomes and deliverables: The applicant will apply several medicinal chemistry principles, namely organic/solid-­‐phase peptide synthesis, peptidomimetic design, and SAR analysis, to further our understanding of how this important class of antibiotics interact with their biological targets. This project will strengthen the applicant’s skills in the areas of organic synthesis and analytical analysis, and will allow the opportunity to see how chemistry and biology interface in a drug discovery setting. The research outcomes will lead to future publications, and will contribute to a high impact research area. Suitable for: This project is open to applications from students with a background in chemistry, preferably 3-­‐4 year students. Primary Supervisor: Dr Karl Hansford. Co-­‐supervisor: Prof Matt Cooper Further info: For further information please contact the Cooper Group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application. Project Title: Is Two Better than One? Vancomycin Dimers to Treat Glycopeptide-­‐Resistant Bacteria


Project Duration: 8-­‐10 weeks Description: Glycopeptide antibiotics such as vancomycin are a last line of defence in the treatment of serious infections caused by drug resistant Gram-­‐ positive bacteria such as MRSA. They inhibit a key step in the biosynthesis of the bacterial cell wall peptidoglycan. Mutations in the peptidoglycan structure have led to widespread vancomycin resistance in recent years. We have developed novel vancomycin derivatives containing additional functional groups that are highly active against Gram-­‐positive bacteria. One recent analogue incorporated two vancomycin molecules and exhibited a very different antibacterial profile, with selectivity for vancomycin resistant species. Expected outcomes and deliverables: The project will focus on the design and synthesis of analogues of this novel vancomycin dimer. The applicant will apply several medicinal chemistry principles, namely organic/solid-­‐phase peptide synthesis, characterisation, drug design, and SAR analysis, to increase our understanding of what structural features contribute to overcoming vancomycin resistance. While primarily synthesis-­‐focused, the student will have the opportunity to observe and learn antimicrobial testing and mode of action studies. The research outcomes will lead to future publications, and will contribute to a high impact research area. Suitable for: This project is open to applications from students with a background in chemistry, preferably 3-­‐4 year students. Primary Supervisor: Dr Mark Blaskovich. Co-­‐supervisor: Prof Matt Cooper Further info: For further information please contact the Cooper Group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application. Project Title: Synthesis of compounds used as fatty acid tales for antibiotic development. Project duration: 8-­‐10 weeks Description: One of the main areas of expertise in the Cooper Group is the development of new antibiotics to treat multidrug-­‐resistant (MDR) gram-­‐ negative pathogens. The aim of the summer research project will be to synthesize a variety of small molecules to be used as fatty acids tales for the polymyxin cyclopeptide antibiotic scaffold. Changing the fatty acid moieties is one of the most direct routes to modify activity and cytotoxicity. Expected outcomes and deliverables: After 8-­‐10 weeks of work the student will be expected to deliver a set of compounds in order to complete a small library of Polymyxin derivatives. After the summer research project is complete,


the student can expect to have a basic knowledge of synthetic chemistry, analytical techniques used in chemistry: Thin Layer Chromatography (TLC), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography Mass Spectrometry (LCMS) among others. This project is oriented in the field of Organic Chemistry/Medicinal Chemistry. Suitable for: This project is open to applications from students with a background in chemistry, 2-­‐3 year students. Primary Supervisor: Alejandra Gallardo-­‐Godoy, Ph.D. Co-­‐supervisor: Prof Matt Cooper Further info: For further information please contact the Cooper Group enquires email: info-­‐coopergroup@imb.uq.edu.au Please ensure contact is made prior to submitting an application.


Craik group Project Title: Disulfide-­‐rich peptides as templates for the treatment of amyloidosis Project duration: 8 weeks Description: Alzheimer's disease is the primary form of dementia, a disease that affects the cognitive faculties of over 250,000 Australians but has no effective cure. The disease, and others including diabetes, is associated with the aggregation of proteins in the body. A possible strategy to treat the disease is to prevent the aggregation of those proteins. In this project, the aim is to use peptides, a promising class of compounds that offers many advantages over small molecules, such as specificity and low toxicity. In particular, the project will focus on the use of cyclic disulfide-­‐rich peptides because they can be used as ultra-­‐stable templates for drug design. The approach is to use a rational structure-­‐informed approach to design inhibitors of aggregation. The project will involve chemical synthesis and purification of peptides, NMR spectroscopy to characterise their structures, and in vitro assays to characterise their activity. Expected outcomes and deliverables: Scholars may gain skills in use of equipment for the purification and characterisation of peptides (i.e. reverse-­‐ phase HPLC, NMR spectroscopy, fluorescence spectrometer), data collection and analysis. Students will also have the opportunity to produce an oral presentation at the end of their project. Suitable for: This project is open to applications from students with a background in chemistry, 3-­‐4 year students, UQ enrolled students only. Primary Supervisor: Dr Conan Wang Further info: Please contact me if you require further information at c.wang@imb.uq.edu.au


Hankamer group Project Title: Structural studies of endosomal sorting complexes hijacked during enveloped virus infection. Project duration: 10 weeks Description: Endsomal sorting complexes (ESCRTs) are a family of multi-­‐ protein assemblies, conserved from yeast to higher eukaryotes, that regulate three fundamental biological processes: the terminal stages of cytokinesis; the biogenesis of multivesicular bodies, and the fission of nascent enveloped viruses from the plasma membrane of infected cells. In all three processes, the ESCRT machinery mediates the deformation of cell membranes, leading to the formation of a budded membrane structures, and ultimately membrane fission. This project is focused on using structural and molecular biology techniques to acquire a better understanding of the molecular mechanisms that drive this membrane remodelling process. A particular focus is on understanding how a wide range of enveloped viruses (including HIV) hijack the ESCRT machinery during infection, opening up the potential to develop novel anti-­‐viral therapies. Expected outcomes and deliverables: A number of functionally important ESCRT complexes are currently being targeted, and it is expected that scholars would be given the opportunity to focus their studies on one such complex of interest. Scholars will develop skills in recombinant protein expression, protein purification and biophysical analyses of protein-­‐protein interactions and multi-­‐ protein complex formation. It is also expected that students will work closely with microscope technicians to analyse the structure of these complexes using high resolution electron cryo-­‐microscopy (Cryo-­‐EM), which will then give the students opportunities to develop skills in image processing and protein structure determination. Suitable for: Suited to 3rd year students with a background in Biochemistry and Molecular Biology, although students from other backgrounds are also welcome to apply. Primary Supervisor: Dr Michael Landsberg Further info: For further info, please contact Michael Landsberg m.landsberg@imb.uq.edu.au


King group Project Title: Venoms to drugs: translating venom peptides into human therapeutics Project duration: 10 weeks Description: The primary focus of this project will be structure-­‐function characterisation and therapeutic development of venom peptides that modulate the activity of neuronal ion channels involved in pain signalling in humans. Molecules that antagonise these ion channels have the potential to be developed as analgesics without the side-­‐effects of current-­‐generation pain killers. Expected outcomes and deliverables: Students will gain skills in a wide variety of biochemical and biophysical techniques, including recombinant protein production, HPLC, NMR and electrophysiology, and they will have an opportunity to generate publications from their research. Students will be required to produce a brief report and an oral presentation at the end of their project. Suitable for: This project is open to UQ-­‐enrolled students only, with a background in chemistry and biochemistry. Primary Supervisor: Professor Glenn F. King Further info: Only one position is available for this project. Applicants must contact Prof. King by email at glenn.king@imb.uq.edu.au


Smythe group Project Title: The Development of HPGD2S Inhibitors for Asthma Project duration: 8 weeks Description: The prevalence, complexity and severity of allergic disease and asthma are increasing worldwide, particularly in developed countries. Currently, most asthma patients manage the disease through a combination of fast-­‐acting relief, including beta2-­‐agonists, and long term medications, such as corticosteroids. However, these therapies provide non-­‐specific, anti-­‐ inflammatory treatment of the underlying disease and only offer patients symptomatic relief. Prostaglandin D2 (PGD2) is a well recognized pro-­‐ inflammatory modulator of asthma and allergic disease. Hematopoietic prostaglandin D2 synthase (HPGD2S) is the enzyme responsible for the overproduction of PGD2 and is a well validated target for therapeutic intervention. Expected outcomes and deliverables: Our research team is focused on drug design using a plethora of medicinal chemistry techniques. Successful applicants will synthesize an array of small molecule inhibitors using a combination of synthetic organic chemistry and peptide chemistry techniques. Students will test these inhibitors in an enzyme assay and develop a structure-­‐activity relationship between the molecules and their biological activity. Throughout the project, students will be given the opportunity to develop and design their own inhibitors. The overall aim of the project will be to improve the potency of a lead compound. Suitable for: The project is open to applications from motivated students with a background in chemistry. Primary Supervisor: A/Prof Mark Smythe Co-­‐supervisor: Dr Christina Kulis Further info: Please contact Christina Kulis c.kulis@imb.uq.edu.au before submitting an application.


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