Masters & PhD Projects

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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

Summary: Currently there is a lack of effective treatments for a broad spectrup of acute and chronic neurological diseases. In many neurological diseases such as Multiple Sclerosis (MS), Motor Neurone Disease (MND) and Alzheimer’s disease, there is no cure, and the majority of patients continue to deteriorate over time. There are some similarities between the diseases in that the overall symptoms are generally driven by the death of neurons or associated oligodendrocytes (cells which envelop adjacent neurons in layers of insulating myelin protein needed for the successful transmission of nerve impulses between neurons).
Our research group is interested in a number of research areas including how we can:
* Modulate the kynurenine pathway to promote mobilization of adult brain stem cells.
* Understand the kynurenine pathway in different phases of Multiple sclerosis to predict disease progression.
* Design potential therapies for Multiple Sclerosis including antibodies directed at specific targets in the kynurenine pathway.
* Investigate novel biomarkers in neurodegeneration (i.e. BCL11b protein) to explore underlying molecular or pathological activity.

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

Summary: Maturity Onset Diabetes of the Young (MODY) is the most common genetic form of diabetes. It represents a good disease model for implementation of genomic mainstreaming, as its point-of-care diagnosis will guide tailored management in those newly diagnosed with diabetes. Under this novel care model, patients attending Diabetes Clinic on campus will be screened via a questionnaire, to identify those who fulfil the criteria for MODY genomic testing. Those fulfilling the criteria will be offered, counseled, and consented by their Endocrinologists (supported by the CGU team if necessary), and testing arranged in the Diabetes Clinic. Results will be given by their treating Endocrinologist, with a referral made to the CGU for those tested positive for follow-up of family implications. Psychosocial stress associated with testing will be evaluated through validated questionnaires at 2 weeks after undergoing testing, and 2 weeks after result disclosure.

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

Summary: There is increasing evidence for pharmacogenomics (PG)-guided psychotropic therapy in patients with mental health illnesses; and increasing evidence for addiction-PG in patients undergoing D&A rehabilitation, in achieving better response/remission compared with conventional therapy. However, the knowledge and acceptability of the Australian clinicians involved in the care of these patients remain unknown. Phase 1: We aim to investigate the knowledge/acceptability and the resource needs of the relevant clinicians to inform wider clinical implementation across both Sydney and Melbourne campuses. Phase 2:  PG testing will be implemented with support needs developed from data generated from Phase 1, in two pilot patient cohorts  – patients with mental health illnesses and patients with D&A addictions. Data from Phase 2 will be prospectively collected, and implementation outcome measured against a set of parameters, including patient response and remission rates, patient and clinician satisfaction. Phase 3 - Cost-saving analysis will be performed, including cost of implementation, number/cost of hospital admissions/adverse drug reactions potentially avoided/aborted had therapy not been guided by PG. Data collected will form part of evidence for future government lobby into Medicare rebate for PG testing.

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

Summary: Therapeutic drug monitoring of antimicrobial agents.

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

Summary: The incidence of thyroid cancer has increased rapidly in the past few decades and is now the 7th most common cancer in Australian women. Thyroid cancer has a low mutation rate but a wide range of natural history from small cancers which can be observed to those which rapidly develop metastatic disease. Our group seeks to improve the knowledge of thyroid cancer biology using sequencing and to understand the clinical outcomes of thyroid cancer. Projects offer the opportunity to collaborate with the University of Sydney Endocrine Surgery Unit based at Royal North Shore Hospital which is the largest treatment centre for thyroid cancer in Australia.

Contact: Dr Anthony Glover at an.glover@garvan.org.au