Masters & PhD Projects

Project: Targeting tumour cell states for more effective treatment
Discipline:
Project level: PhD
Supervisor: Team led by Professor Joseph Powell
Project commencement: immediately
Project Outline: Significant obstacles hampering the development of effective brain cancer therapeutics include tumor heterogeneity, the persistence of incompletely understood cancer stem cells that give rise to cancer recurrence, and the plasticity of tumour cell states. Our brain cancer research program covers many cancer types, but is predominantly focused on IDH wild-type glioblastoma, the most common adult primary brain cancer, which exemplifies these obstacles. Following radiotherapy and chemotherapy, the median survival time is 14 months, and the 5-year survival rate less than 10%.
The tumour cells within a glioblastoma reside in a variety of distinct cell states. A cell state is a specific genomic profile that leads to differences in the way tumor cells behave. In IDH wild-type glioblastoma, these states are composed of two main compartments: a larger differentiated cell compartment that forms the basis of our understanding of the genomic and molecular underpinnings of the disease; and a smaller, less well-characterized compartment of cells with aggressive stem-like capabilities. The molecular and genomic heterogeneity, and the persistence of a subpopulation of cancer cells with stem-like properties following radiotherapy and chemotherapy, are believed to be the main causes of resistance to treatment and the associated extremely poor outcomes.
To add to the complexity of this disease, cancer cells can dynamically shift between the non-aggressive and the chemotherapy-resistant stem-like states. An important implication of this work is that the aggressiveness of a given carcinoma derives not only from its existing content of stem-like cells, but from the proclivity of the non-aggressive cells to generate stem-like cells.
This PhD project will leverage information gained from cellular genomics experiments that have identified specific tumour cell states in brain cancers. Analysis has uncovered the genomic drivers of those cell states, and predictions on if existing drugs are able to eradicate the more aggressive cell states, and prevent the plasticity that enables non-aggressive cells to spontaneously enter into the stem-like state. The research will utilize cell organoid models to investigate how specific cell states respond to treatments, developing pre-clinical evidence of the efficacy of new therapeutic strategies.
This PhD position is based in the Garvan-Weizmann Centre for Cellular Genomics, and will join a productive large-scale brain cancer research project.
This project is suitable for someone with a MBBS. In addition to the PhD project, it is envisioned that the student will also undertake a 0.2FTE (1 day per week) clinical position in St Vincent’s Hospital Oncology department.
Contact: Professor Joseph Powell on email j.powell@garvan.org.au
Project: Investigating glucose regulation in people living with obesity before and after bariatric surgery.
Discipline: Endocrinology, obesity reserach
Project level: PhD
Supervisor: Team led by Dr Dorit Samocha-Bonet
Project commencement: immediately
Project Outline: The study is a collaboration between researchers at the Garvan Institute of Medical Research and endocrinologists and bariatric surgeons from 5 hospitals across Sydney. The study will be performed at the Garvan Institute of Medical Research (Darlinghurst). Background in either health sciences or medicine are appropriate. The study is approved by the St Vincent’s Hospital Human Research Ethics Committee (reference 2020/ETH02405, “Reverse engineering insulin secretion in health and disease – Part 2”).
Contact: Dr Dorit Samocha-Bonet at d.samochabonet@garvan.org.au
Project: Discovering a cure for childhood inflammatory disease
Discipline: Biochemistry, Immunology, Pharmacology
Project level: PhD / Honours
Supervisor: Team led by Prof Mike Rogers and Dr Marcia Munoz
Project commencement: immediately
Project Outline: We are seeking enthusiastic and self-motivated PhD and Honours students for projects on an autoinflammatory disease called mevalonate kinase deficiency (MKD), a devastating disorder of the innate immune system that usually becomes apparent in early childhood and can be fatal. Using new mouse models as well as samples from humans, this is an exciting opportunity to discover new insights into the poorly understood genetic, molecular and biochemical features of MKD, as well as identify and test new therapeutic strategies. Projects will involve a wide variety of standard laboratory techniques including cell culture, microscopy, western blotting and quantitative PCR, as well as cutting-edge approaches including single cell RNAseq and intravital 2-photon imaging.
Contact: Professor Mike Rogers at m.rogers@garvan.org.au
Project: Decoding inherited heart disease
Discipline: Molecular Cardiology
Project level: Projects can be tailored to all levels
Supervisors: Professor Diane Fatkin & Dr Claire Horvat
Project commencement: Variable
Summary: This project will use cutting-edge whole-genome sequencing to identify disease-causing genetic variants in families with dilated cardiomyopathy and/or atrial fibrillation.
Contact: Professor Diane Fatkin at d.fatkin@victorchang.edu.au
Project: Genotype-phenotype correlations in families with dilated cardiomyopathy
Discipline: Molecular Cardiology
Project level: Projects can be tailored to all levels
Supervisors: Professor Diane Fatkin & Dr Renee Johnson
Project commencement: Variable
Summary: This project involves genetic analysis of families with dilated cardiomyopathy and correlation with genetic variants with clinical status. The potential impact of background genetic variation and lifestyle factors on the disease phenotypes will be investigated.
Contact: Professor Diane Fatkin at d.fatkin@victorchang.edu.au
Project: Gene-environment interactions in familial dilated cardiomyopathy: insights from zebrafish models
Discipline: Molecular Cardiology
Project level: Projects can be tailored to all levels
Supervisors: Professor Diane Fatkin & Dr Inken Martin
Project commencement: Variable
Summary: This project will use genetically-engineered zebrafih models to evaluate the functional effects of human genetic variants and the potential modifying effects of environmental factors. It involves the use of cutting-edge tools to assess heart function in embryonic and adult fish.
Contact: Professor Diane Fatkin at d.fatkin@victorchang.edu.au
Project: The role of the TGFb superfamily cytokine MIC-1/GDF15 in the regulation of inflammatory responses
Discipline: Immunology, metabolism, inflammation
Project level: PhD
Supervisor: Team led by Prof Samuel Breit
Project commencement: immediately, contingent on PhD scholarship funding
Contact: Prof Samuel Breit at s.breit@amr.org.au
Project: The role of the TGFb superfamily cytokine MIC-1/GDF15 in regulation of tumor immunity
Discipline: Immunology, metabolism, inflammation, cancer biology
Project level: PhD
Supervisor: Team led by Prof Samuel Breit
Project commencement: immediately, contingent on PhD scholarship funding
Contact: Prof Samuel Breit at s.breit@amr.org.au
Project: The characterisation of biological pathways and other biomarkers for the development of treatment and diagnostic strategies in MS and neurodegenrative diseases.
Discipline: Neurology
Project level: Project can be tailored to all levels
Supervisor: Bruce Brew AM, Dr Michael Lovelace & Dr Gayathri Sundaram
Project commencement: Variable
AMR PhD scholarship topups are available to bring tax free scholarships to a maximum of $33,800.
Other Projects:
1) Pathophysiological characterisation of Kynurenine pathway activation and dysregulation in Multiple Sclerosis. (Tissue microarray)
2) Genetic characterisation of Kynurenine pathway activation and dysregulation in Multiple Sclerosis. (Taqman array)
3) Single cell RNA profiling of mouse & human induced pluripotent stem cells during precursor phase and differentiation - discovery of therapeutic strategies for neurodegenerative diseases.
4) A putative blood brain barrier permeable kynurenine 3-monooxygenase inhibitor intervention in a Multiple Sclerosis Mouse Model.
5) Adaptive and behavioural changes in KMO and QPRT conditional knockout mice: Relevance to Multiple Sclerosis.
6) Does the MS drug Laquinimod regulate Kynurenine pathway in mouse and human neural stem cells during neuroinflammation?
7) How does the neurotoxin Quinolinic acid affect the regenerative capacity of human neural stem cells?
8) Role of Kynurenine Pathway in Monocytes in Multiple Sclerosis.
Contact: Prof Bruce Brew at Bruce.Brew@svha.org.au, Dr Michael Lovelace at m.lovelace@amr.org.au or Dr Gayathri Sundaram at g.sundaram@amr.org.au
Project: Implementing a novel genomic mainstreaming care model.
Discipline: Clinical Genetics
Project level: Honours/Masters
Supervisor: Dr Kathy Wu
Project commencement: Variable
Contact: Dr Kathy Wu at kathy.wu@svha.org.au
Project: Informing resource needs of pharmacogenomics-guided therapy in patients with mental health illnesses and drug/alcohol addictions: for SVHA campus-wide implementations and beyond.
Discipline: Clinical Genetics
Project level: Honours/Masters/PhD
Supervisor: Dr Kathy Wu
Project commencement: Variable
Contact: Dr Kathy Wu at kathy.wu@svha.org.au
Project: Antimicrobial Therapeutic Drug Monitoring (TDM)
Discipline: Microbiology and Infectious Diseases
Project level: ILP/Honours/Masters/PhD
Supervisor: Professor Deborah Marriott
Project commencement: Variable
Contact: Professor Deborah Marriott at dmarriott@stvincents.com.au
Project: Understanding biology and outcomes of thyroid cancer
Discipline: Cancer Biology, Endocrine Surgery
Project level: Projects can be tailored to all levels
Supervisor: Dr Anthony Glover
Project commencement: Variable
Contact: Dr Anthony Glover at an.glover@garvan.org.au