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.
Structure And Composition Of The Pre-T Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
In order to recognize a wide variety of pathogens, humans produce many different T cell receptors (TCRs) by the process of gene-rearrangement. However, gene-rearrangement may not always lead to a functioning TCR. We are studying the pre-TCR protein that is responsible for monitoring the success of gene-rearrangement and is thus essential for the formation of a robust immune system. Understanding pre-TCR function will lead to new treatments for immune related diseases.
Matching Supply And Demand: How Does Metabolism Fine-tune Signal Transduction?
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Insulin controls nutrient traffic and disrupting its actions are linked to many diseases: type 2 diabetes, cancer, heart disease. Here, I will test a novel hypothesis that our cells’ metabolic rate, defined by the balance between nutrient supply and energy expenditure, controls how cells respond to insulin. These metabolic regulatory nodes would play a major determinant of many essential functions linked to human health, and thus provide novel therapeutic targets for numerous diseases.
Determining The Molecular Basis Of Tumour Cell Multidrug Resistance: Structural And Functional Analysis Of Breast Cancer Resistance Protein
Funder
National Health and Medical Research Council
Funding Amount
$325,396.00
Summary
Around 40% of human tumours develop resistance to chemotherapeutic drugs; a trait most commonly acquired by the increased expression of membrane proteins that remove a broad spectrum of molecules from the cell. This project aims to determine the structure of the human breast cancer resistance protein (BCRP), a protein of particular importance in this process. The structure of BCRP will provide a scaffold for the design of drugs aimed at inhibiting chemotherapy drug resistance.