Honours Projects at Other Institutes
Prince of Wales Hospital
Dr Tim Brighton
Project 1: Investigation of a case of acquired von Willebrand’s Disease. This project revolves around a patient with apparent acquired VWD. The project involves purification of patient immunoglobulin, proving patient’s antibody reproduces the phenotype, and establishing new assay to detect auto-antibodies to VWF. Genotyping the patient to exclude heritable Type II VWD will be required. The work would be completed by literature review and preparing a manuscript for publication.
Project 2: Investigation of Type III VWD.The Dept of Haematology has 5 known kindreds of Type III von Willebrand’s Disease. This project would involve detailed family investigations of phenotype and laboratory assays. DNA would be collected, extracted, amplified and direct sequenced to identify mutations in the cases and parents. The size of the VWF gene makes it more efficient to screen for mutations in and deletions of exons by PCR amplification and denaturating gradient gel electrophoresis prior to sequence analysis of exons in which mutations are suspected.
Project 3: Characterisation of Familial Thrombocytopenia.
Candidate genes carrying mutations account for approximately 50% of cases of familial thrombocytopenia described in the existing literature. The project will focus on characterising the gene(s) involved in several kindreds of familial thrombocytopenia within the Department. Linkage analysis using single nucleotide polymorphisms will be used to identify/exclude candidates in these families, followed by sequence analysis of relevant genes. Genome-wide snp analysis may be required where no clear candidates emerge from the initial analysis.
Project 4: Characterisation of Platelet Dysfunction in Patients with ITP.
Occasional patients with immune thrombocytopenia have unusually severe bleeding given their platelet count and platelet dysfunction. In these cases the autoantibody inhibits platelet function. This project will focus on 2 cases and involve total Ig and IgG preparations from patient’s serum, platelet aggregation experiments to reproduce the platelet aggregation defect, and determination of the specificity of the autoantibodies.
Project 5: Characterisation of Scott Syndrome Platelets. Scott Syndrome is a rare poorly characterised but fascinating inherited platelet membrane disorder. This project will continue ongoing research into kindreds with bleeding who may have Scott Syndrome or other functional platelet defects. The work will involve a variety of functional platelet assays (aggregation, thrombin generation), flow cytometric analysis, and novel laboratory assays to be established. If individuals with Scott Syndrome are found, characterisation of the gene(s) involved would potentially make a significant contribution to platelet physiology.
Dr A Graudins / A/Prof P Thomas (Department of Emergency Medicine)
Project 1: Characterisation of novel neurotoxins from the venoms of Australian snakes. Assessment of in-vitro toxicity and efficacy of current antivenoms in toxicity reversal of lesser known snake venoms. Current work includes isolation and characterisation of PLA2 neurotoxins from Australian Death Adder venoms. Projects aim to expand to other snake families which contain venoms where there has been little work to assess neurotoxic potential.
Project 2: Novel uses for 'old' antidotes in an animal model of cardiac drug toxicity. Assessment of the efficacy of established antidotes not commonly used in the treatment of toxicity resulting from poisoning with various cardiotoxins where there may not be a response to currently accepted therapies for these poisons (specifically including cyclic antidepresants, calcium channel blockers- verapamil, and other membrane-active drugs such as venlafaxine).
Dr Jonathan Howard (Department of Microbiology, Virology Division)
Project: Congenital viral infections Cytomegalovirus is the leading cause of congenital viral infection. However, its role in stillbirth has not yet been thoroughly investigated. The projects will investigate (1) novel methods to detect congenital CMV infections in asymptomatic and symptomatic babies (2) role of CMV in the regulation of cellular proteins expressed during placenta development (3) screen other possible aetiological agents related to congenital infections.
Skills learnt: Multiplex PCR, total nucleic acid extraction, cell culture.
Dr KC Leung (Department of Microbiology, Virology Division)
Project: Molecular mechanisms for viral destruction of insulin-producing cells. 1 place available
This project investigates the mechanism by which enteroviruses induce cell death and/or functional impairment of pancreatic beta-cells. A wide range of molecular techniques will be applied to study the viral ability to cause cellular and functional damages of insulin-producing cell cultures.
A/Prof W Rawlinson (Department of Microbiology, Virology Division)
Pathogenesis of viral diseases including human cytomegalovirus (HCMV) and the animal model murine CMV, Hepatitis C virus, noroviruses, and respiratory virus infections. Role of viruses in congenital infection, hepatitis, breast cancer, gastroenteric disease, and resistance to antiviral treatments.
Dr G Scott / A/Prof W Rawlinson (Department of Microbiology, Virology Division)
We have projects investigating the pathogenesis of cytomegalovirus (CMV) infection in neonates and transplant recipients. In particular, we are investigating the mechanisms of CMV transplacental transmission, as well as the viral and host factors that influence outcomes of CMV infection in transplant recipients.
Project 1: Replication of CMV in placental trophoblast cells - influence of strain variation
Project 2: Characterisation of CMV mutations that confer antiviral resistance
Dr Sacha Stelzer-Braid, (Department of Microbiology, Virology Division)
Project: An estimated 3% of the world population (or 200 million people) and 1% of Australians are infected with HCV. Approximately 70% of all people with HCV cannot clear the virus naturally, and develop a chronic infection that can lead to liver cancer and death. HCV is difficult to treat or develop a vaccine for because HCV exists within an individual as a spectrum of minor variants termed quasi-species, which help HCV evade the host immune system. A project is available on analysis of viral quasispecies and analysis of viral genetic change over time with treatment.
Skills learnt: PCR, sequencing, genome assembly, mutation analysis
Victor Chang Cardiac Research Institute
A/Prof D Fatkin (Molecular Cardiology Program)
Project 1: Identification of novel disease genes for familial AF. This study is examining DNA from AF patients for mutations in candidate genes.
Project 2: Characterisation of the atrial ³environment². This study will use cell models to evaluate the effects of mechanical stress on atrial wall properties and AF development.
Skills learnt: DNA and RNA extraction, PCR, sequencing, mutation analysis, genome analysis, cell culture, molecular and cell biology techniques, stretch studies.
Prof M Feneley / Dr J Yu (Cardiac Mechanic Research Program)
The overall research strategy is to employ a series of different transgenic/knockout mouse models to dissect the different candidate pathways to the induction of left ventricular hypertrophy (LVH) in low-renin and high-renin LV pressure overload by cardiac-targeted inhibition of critical steps in each pathway.
Project 1: /TgGqI mouse/. This mouse has inhibition of Gq receptor function. This project will examine relative role of activation of Gq receptors in the induction of pressure overload LVH in the presence and absence of elective renin levels.
Project 2: /GSK3//b// mouse/. This mouse has effective blockade of the calcineurin-mediated pathway to LVH induction. This project will explore the relative role of the calcineurin pathway in induction of pressure overload LVH in the presence and absence of elective renin levels.
Dr M Wouters
Project 1: Development of a bioinformatic tool for candidate gene prediction. The project involves development of a module of our
candidate gene prediction system, GenTrepid, to further enhance its prediction capabilities. Modules available for development are
* Extension of the system to predict drugs suitable for targetting
candidate genes
* Use of the system to evaluate data of medium significance in
genome-wide association studies
Skills learnt: Programming in perl, use of the Unix operating system
The Children’s Hospital at Westmead
Dr Jennifer Byrne (Oncology Research Unit)
The molecular basis of mitotic deregulation by D52-like proteins
Dr D Catchpoole (Oncology Research Unit)
Project 1: Examination of the association of morphological, molecular and genetic prognostic indicators in different cell types within the childhood neuroblastoma tumours using laser capture microdissection
Project 2: Molecular diagnosis of childhood malignancy using microarray technology
St George Hospital
Dr N Chapman (Thrombosis and Bleeding Disorders Research Unit)
Project 1:A prospective observational study of thrombosis prophylaxis in surgical patients. This project involves interacting with patients following surgical procedures for their consent to the study and a study follow up interview, and includes medical chart review, database design, data entry and analysis and will expose the student to the ethical processes required to conduct clinical research. It may also be conducted in conjunction with a qualitative study of surgeons attitudes to thrombosis prophylaxis and will result in recommendations for ways to improve Australian surgical patient care.
Bioanalytical Mass Spectrometry Facility
Dr V.Wasinger
Project :Proteomic biomarkers in the assessment of Inflammatory Bowel Disease; severity and prediction of treatment response.
Skills learnt: Application of proteomic technologies for elucidation of novel markers using in-house developed technologies, fractionation, liquid chromatography and 'state of the art' mass spectrometry techniques, quantitative and qualitative data evaluation and multivariate stat analysis. Project will involve liasing with clinicians at Bankstown and Concord Hopsitals in association with A/Prof Rupert Leong.