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The majority of stroke results from focal brain infarction, followed by substantial secondary excitotoxic damage in the surrounding areas. Tau has been shown to contribute to excitotoxicity and neurodegeneration in mouse models of Alzheimer’s disease (AD). Preliminary data show that tau reduction also protects against excitotoxic damage after experimental stroke. We aim to dissect the molecular mechanisms of stroke using a tau-deficient mouse model.
Despite the clear epidemiological evidence that physical activity can reduce breast cancer recurrence and risk, little is know about the mechanisms. The aim of this project is determine the metabolic pathways and immunological effects of exercise in preclinical breast cancer models and in breast cancer patients, and to determine if there are synergistic effects with current systemic therapies.
Defining The Cellular Basis For Therapeutic Angiogenesis: Characterisation Of Endothelial Progenitor Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$100,943.00
Summary
Cardiovascular disease is the leading cause of death in the Australia. Endothelial progenitor cells (EPCs), similar to stem cells, have strong self-renewal capabilities and the ability to mature further. There has been immense interest in using EPCs as they are believed to have a role in the growth and repair of blood vessels. This research systematically studies two candidate EPCs, the early EPC and the outgrowth EPC (OEC), and potentially paves the way for using EPCs to treat heart disease.
Understanding And Manipulating The Epigenetic Networks That Define Osteosarcoma
Funder
National Health and Medical Research Council
Funding Amount
$80,467.00
Summary
Osteosarcoma is the most common type of bone cancer and the fifth most common form of cancer in children. Although osteosarcoma begins in bones, the cancer often spreads to other parts of the body. Patients have a very poor chance of survival if their cancer has spread. We will use mouse and human models of osteosarcoma to improve our understanding of how the cancer is different from the normal bone forming cells. This information will help us to find new treatments to improve patient outcomes.
The Role Of Th17 And Tregs In The Development Of Tolerance And Rejection In A Murine Model Of Renal Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$110,068.00
Summary
In clinical transplantation, rejection remains the greatest problem in determining both short and long-term patient outcomes. Tolerance, the ability of the body to accept a transplant without immunosuppressive drugs, remains an as yet unattained goal. The aim of this project is to examine the mechanisms by which the initial immune response (innate immunity) affects the development of tolerance or rejection in a mouse model of kidney transplantation.
Pro-apoptotic Therapies For The Treatment Of Mycobacterium Tuberculosis Disease And Latent Infection
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Programmed cell death has an important role in our ability to fight organisms. Upon infection, processes result in activation of death-inducing cascades, resulting in death of cell and pathogen. M. tuberculosis, an escalating health problem, has developed mechanisms to prevent this, leading to latency. This study, which uses mouse M.tb models, hypothesises that reversal of these mechanisms, using drugs currently in trial in leukaemia (ABT-737 & BV6), may lead to clearance of infection.
Hypothalamic Regulation Of Appetite And Energy Homeostasis In Prader-Willi Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$39,987.00
Summary
Prader-Willi syndrome (PWS) is a genetic disease affecting 1/~15 000 people. It causes insatiable appetite and often morbid obesity, as well as other developmental problems. It is thought that there is a defect in the way that the brain regulates eating behaviour in PWS, but the exact mechanism is still unknown. This study proposes to explore metabolic and genetic factors contributing to the appetite disorder in PWS. It will also explore new ways of treating excessive appetite.
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
Cell Survival Pathways As Potential Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$142,914.00
Summary
Cancer cells are characterised by their capacity for relentless growth, survival and evasion of cell death. This proposal will use patient derived xenograft models of primary breast cancer to test the hypothesis that addition of BH3-mimetics could improve response to anti-HER2 therapy. This technique involves transplantation of patient tumours into immune-compromised mice. This represents a useful method for testing new agents.
Investigating The Role Of Mucosal Associated Invariant T (MAIT) Cells In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$122,566.00
Summary
Tuberculosis (TB) is a deadly infectious disease that kills 2 million people per year worldwide. If we are to eliminate this disease, we urgently need a new TB vaccine. I plan to look at what role a newly discovered type of T cell might play in TB infection and to see whether these cells can be manipulated by vaccination. This work will help us to understand more about the body’s first response to TB infection and how we can use this response in the design of new TB vaccines.