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Unravelling How Protein Signalling Networks Integrate To Control T Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Rational design of drug combinations to manipulate the immune response requires an understanding of how different signals work together to control cell behaviour. The PIM kinase proteins are known to regulate important properties of immune cells, including division and death and when dysregulated can lead to cancer. I will perform a comprehensive, unbiased investigation of how the PIM kinases interact with other protein signalling pathways to control the immune response in health and disease.
The initial step of T cell activation of how the external ligand binding is translated to an increase of receptor phosphorylation at the cytoplasmic side is remain poorly understood. It is believed that the loss of immune recognition in cancer and over reactivity in auto-immune diseases are caused by abnormality of this transmembrane signalling transduction. Clarification of this molecular machinery can provide a molecular basis of those diseases and guidelines of more effective therapies.
The Role Of Self Reactive T Cells In The Normal TCR Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$363,601.00
Summary
The immune system is highly regulated and sophisticated in order to distinguish foreign invaders from our own body. Once control is lost in this system, mistakes can happen, and autoimmunity, attack of ones self may result. Surprisingly potentially dangerous ‘fighter’ T cells can be readily found in healthy individuals whom are free from autoimmunity. The aim of this project is to understand how we can survive with these potentially harmful T cells around and what may activate them.
The Effect Of Follicular Helper T Cells (TFH) On AID Regulation And Selection Of High Affinity Germinal Centre B Cells.
Funder
National Health and Medical Research Council
Funding Amount
$430,964.00
Summary
An integral component of an immune response to foreign pathogens is the production of antibodies by B cells. However, if antibodies react to self-antigens (human molecules rather than bacteria or viruses) they may also cause autoimmune diseases such as lupus. This research project is investigating the mechanisms that control antibody generation by B cells, and how these are dysregulated in autoimmune diseases, such as lupus.
Investigation Of Small Molecule Interactions With The Human Leukocyte Antigen And Their Role In Non-infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The Human Leukocyte Antigens (HLA) play a key role in the immune system helping the body differentiate healthy from diseased cells. Numerous autoimmune diseases and adverse drug reactions are associated with specific HLA variants. This study seeks to unlock the mechanisms behind these diseases, investigating how small molecules including drugs interact with the HLA to make healthy body cells seem foreign. This research has the potential to inform strategies for disease avoidance and management.
T-cells: The Key To Unlocking Immunity Against Aggressive Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
By investigating several aspects of patients’ immune defenses against the cancer cells in Diffuse large B-cell lymphoma, this project will provide critical insights on ways to harness the patient’s own immune system to effectively mount anti-tumour responses. These results will pave the way for future therapeutic strategies to successfully treat and prevent lymphoma.
Molecular Regulation Of Tim3 Signalling In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Chronic inflammatory diseases like multiple sclerosis and cancer can be rectified via interventions of T cell checkpoint pathway. Tim3 is a T cell checkpoint molecule that is gaining extreme interest in these diseases. Here, we aim to identify molecular mechanism(s) to suppress or enhance Tim3 signalling in effector T cell, potentially leading to the development of therapeutic intervention to treat autoimmune disorders and cancers.