Masters & PhD Projects

Project: Tracking B cell fate decisions in time and space

Discipline: Immunology

Project level: PhD/Honours

Supervisor: Conjoint Associate Professor Tri Phan

Project Commencement: January 2019

Summary: B cells make antibodies that protect us from infection. However, B cells can also make antibodies that attack us and cause autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. By using state-of-the-art intravital two-photon microscopy and single cell sequencing technologies, this project aim to track the fate of B cells as they make the cell fate decision to become an antibody secreting plasma cell in the setting of vaccination and autoimmunity. By understanding how this process is regulated in space and time we hope to develop new strategies to make better vaccines and treat autoimmune diseases.

Contact: Conjoint Associate Professor Tri Phan at t.phan@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: Using genomic technology to study the rogue cells that cause autoimmune disease

Discipline: Immunology

Project level: PhD/Honours

Supervisor: Prof Chris Goodnow & Dr Joanne Reed

Project commencement: Variable

Summary: Autoimmune disease occurs when immune cells "go rogue" and attack healthy parts of the body, instead of attacking infectious microbes. There are over 100 different autoimmune diseases, which affects 5-10% of the population and are a major cause of chronic disease in our society. Without a cure, individuals afflicted by these diseases face ongoing clinical care based on suppresing the whole immune system. Current clinical practice treats the symptoms of disease rather than the cause because we don't have a way to identify and eradicate the idividual cells of the immune system that have gone rogue. Our group has developed innovative cellular genomics technology incorporating single cell sequencing and multi-parameter flow cytometry to identify and isolate rogue B cells from patients with the autoimune diseases Sjogren's syndrome and lupus. This research has uncovered therapheutic targets and allowed us to trace the evolution of these disease causing cells.

We are currently recruiting enthusiastic students who are interested in using cutting-edge genomic technology to learn about fundamental mechanisms of the immune system and impact treatment strategied and outcomes in patients with autoimmune diseases.

Contact: Dr Joanne Reed at j.reed@garvan.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

 

Project: Abrreviated Breast MRI for breast cancer detection 

Discipline: Medical Imaging, Oncology

Project level: Honours/Masters/PhD

Supervisors: Dr Linda Borella & A/Prof Elgene Lim

Project commencement: Variable

Summary: Abbreviated Breast MRI i(AB-MR) is a new application of Breast MRI for breast cancer detection. Breast MRI is the most sensitive imaging test available for breast cancer detection, able to detect up to three times more cancers than mammograms. Until recently MRI has not been widely used for breast cancer screening due to limitations with availability, cost, length of scans (up to 30 minutes) and misperceptions about sensitivity and specificity. AB-MR is a new short protocol MRI that takes less than 10 minutes to perform. Studies have shown it to be equally effective as traditional long protocol MRI scans for breast cancer detection in women at average to mildly elevated risk. St Vincent’s Clinic Medical Imaging is the first practice in Sydney to offer this examination. There is good international data to support use of AB-MR as a screening test in women at average and mildly elevated risk of breast cancer. There is lacking data on the use of AB-MR for women at high familial risk and the use of AB-MR to determine extent of disease in women being currently managed for proven breast cancer. This study aims to add to the international research pool to support the use of AB-MR as a screening and diagnostic test. Study parts include: (1) Analyse and publish outcomes from early experience of AB-MR at SVCMI&NM (2) Retrospective comparison of AB-MR to long protocol MRI scans performed for women at high risk and those being currently managed for breast cancer (3) Establish a database for breast MRI patients from which trends can be identified and future studies may arise. This study has been Ethics Approved.

Contact: Dr Linda Borella at lborella@svmi.com.au