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Targeting Vitamin-reactive T Cells For Enhanced Immunity
Funder
National Health and Medical Research Council
Funding Amount
$2,590,576.00
Summary
A specialised set of T cells called mucosal-associated invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are often breached, e.g. respiratory tract and intestinal mucosa. This study seeks to define the molecular signals driving the function of MAIT cells, particularly during infections. This information may lead to methods tailored to manipulating MAIT cells therapeutically.
Characterization And Targeting Of Precursor Exhausted T Cells (TPEX) For The Treatment Of Chronic Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,009.00
Summary
The recent discovery of precursor exhausted CD8 T cells (TPEX) has not only allowed us to conceptualize our understanding of how chronic T cell responses are maintained over long periods of time, but also resulted in a new understanding of the mechanisms underpinning checkpoint inhibition. I will undertake critical characterization of these TPEX in chronic viral infections with the goal to reveal phenotypic and functional properties, which will serve as potential novel targets for immunotherapy.
The Role Of Mucosal-Associated Invariant T Cells In Protective And Aberrant Immunity
Funder
National Health and Medical Research Council
Funding Amount
$620,205.00
Summary
Despite their prevalence and potential therapeutic value, MAIT cells remain the least studied of all T cells. This program seeks to do paradigm shifting research into the role of MAIT cells in protective immunity to microbes and allergies. Thereby this project will significantly advance fundamental knowledge on MAIT cell biology and could furnish novel immunotherapeutic agents with an enormous potential as alternatives to microbial and allergy treatments, areas of tremendous clinical need.
Improving The Diagnosis, Treatment And Prevention Of Infectious Diseases In Children
Funder
National Health and Medical Research Council
Funding Amount
$2,410,857.00
Summary
I am a clinician scientist whose research team bridges the gap between laboratory and clinical research to reduce the impact of childhood infectious diseases worldwide. The two main themes within my research program are: 1. Improving the diagnosis of childhood tuberculosis (TB) in resource-poor settings. 2. Understanding how BCG, the vaccine used to protect against TB, reduces other childhood illnesses, including non-TB infections, allergies, eczema and asthma.
Defining The Role Of B Lymphocytes In Breast Cancer At Single-cell Resolution
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
B cells, a type of immune cells, are likely protective against breast cancer, albeit through unknown mechanisms. Over the next 5 years I will apply high-resolution profiling and imaging of B cells within breast cancer biopsies to understand their contribution and identify novel clinical targets, leading to better patient outcomes.
Mechanisms Of Cell Death Driven Inflammation In The Skin
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Inflammatory skin conditions are a leading cause of disease. Current therapies treat symptoms not causes of inflammation. Skin cells constantly interact with cells of the immune system, and with a diverse array of helpful and harmful microorganisms. My data suggest a role of the skin flora and resident immune cells in the initiation and progression of skin disease. I will investigate how the microbiota and immune cells can initiate cell death and drive excessive immune responses in the skin.
Developing Novel Therapeutic Approaches To Treat Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,173,545.00
Summary
Progression of chronic kidney disease (CKD) to endstage is characterised by inflammation and fibrosis. No current treatment effectively halts CKD progression. We are using protective immune cells to treat CKD and have invented a genetically-engineered immune cell which uses damaging inflammatory signals to switch them into protective cells which reverse inflammation and fibrosis where they occur, to prevent progression of CKD and other diseases, such as those of heart, lung and liver.
Tailoring Dendritic Cell Diversity To Advance Effective Immunotherapies
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Dendritic cells (DCs) constitute the first line of defense against infection and cancer. To achieve this feat, DC have evolved into a sophisticated network of specialized subtypes, although how this diversification process occurs is yet to be fully clarified. We have uncovered a new molecule, termed DC-SCRIPT, which has a key role in establishing the DC network, specialization and function. This offers crucial new clues as to how to manipulate DCs to either boost or dampen the immune system.
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
Deciphering Mechanisms Underlying Breast Cancer To Improve Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$3,314,215.00
Summary
Breast cancer is a highly heterogeneous disease. Patients are often treated in a ‘one size fits all’ approach, but response to therapy remains disparate. To more effectively personalise therapy, there is a pressing need to define the precise cell types and initiating genetic events that give rise to breast cancer. This application is centred on understanding mechanisms of breast cancer initiation and progression, with the potential of identifying new prognostic markers and therapeutic targets.