Regulation Of The Signalling Efficiency Of The T Cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$456,557.00
Summary
An immune response starts with activation of the T cell antigen receptor (TCR). How T cell receptor signalling begins, however, is not well understood. We have developed a novel imaging approach that allows us to directly observe what happens after an antigen binds to the receptor. The research will provide mechanistic insights into how T cells sense and discriminate antigens. This knowledge will aid the development of cancer immunotherapies and vaccines.
Understanding The Molecular Basis Of Epididymal Maturation: How Does The Epididymis Modify Spermatozoa, Allowing Them To Recognise The Egg ?
Funder
National Health and Medical Research Council
Funding Amount
$585,898.00
Summary
Male infertility is a significant clinical problem affecting one in twenty Australian men. A common feature of this condition is the sperm’s inability to recognize the egg. Sperm gain this property as they transit an organ known as the epididymis. We have produced genetically modified mice with a specific epididymal defect that prevents sperm-egg recognition. This study will examine the structure of these defective sperm to generate new insights into the molecular basis of sperm-egg interaction.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.
The Novel CXCR4/CCR7 Heterodimeric Chemokine Receptor Is A Key Determinant Of Breast Cancer Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$461,252.00
Summary
Novel cellular receptor has been identified that works as a switch to turn on cellular functions that are responsible for the metastatic dissemination of cancer cell to distant organs. The make-up and regulatory mechanisms of this novel receptor will be studied together with its potential utility as the marker of metastatic breast cancer.
Membrane Attachment And Components Of The Ca2+ -triggered Release Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$386,498.00
Summary
Understanding and harnessing the fundamental cellular process of secretion will provide a wealth of new approaches to addressing problems associated with aging & disorders that are major health care burdens (e.g. neurodegeneration & diabetes). Understanding the vesicle docked state, and the contributions of different molecular components to the release process provides for unique insights into the underlying molecular mechanisms, thereby enabling safe, targeted control of this critical process.
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
New Mediators Of GPCR-growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$607,842.00
Summary
Hormones bind to receptors on the surface of cells. Receptors can modify each other’s function and this “cross-talk” is important for the receptors for a peptide hormone (termed angiotensin) and a growth factor receptor (EGFR), which are major regulators of the cardiovascular system. We have identified a number of mediators of the angiotensin-EGFR crosstalk and this current grant aims to use molecular and cellular and in vivo approaches to examine the molecular basis of their actions.
Mechanism Of Epidermal Growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. We believe that the same cell processes are also involved in cancer cell growth and by understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease and its relationship to uncontrolled growth will evolve.
The neuronal synapse is very tightly regulated by proteins that control both the timing and the amount of neurotransmitter release and neuronal stimulation. Defects in this synaptic signal are linked to diseases including epilepsy, autism and dementia. In this study we will determine the molecular details of how proteins called SNAREs control neurotransmission in the human brain.