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.
Identifying Novel Antimalarial Targets Using ENU Mutagenesis In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$760,170.00
Summary
Malaria is estimated to cause 1.2 million deaths per year. The malarial parasite has developed resistance to most drugs and new drugs are needed. We aim to mimic the protective red blood cell diseases common in human populations in malarial endemic areas by identifying host targets that are important in parasite growth.
Molecular Regulation Of Pluripotency In The Mammalian Germline
Funder
National Health and Medical Research Council
Funding Amount
$611,935.00
Summary
Germ cells generate sperm in males or oocytes in females. In males, germ cell numbers are tightly controlled in the embryo, with too few germ cells causing infertility, and unrestrained germ cell numbers leading to testicular cancer. We have discovered a molecular mechanism that regulates germ cells in the embryo, and propose to study in mice how this regulation is accomplished and the consequences of defective regulation, in order to learn more about how infertility and testis cancer arise.
Precision Epigenetics: Targeting The Epigenome To Treat Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,940,576.00
Summary
Epigenetic marks are changes made to the DNA that allow genes to be switched off in some cells and switched on in others. These marks are critical to normal development and often go wrong in disease. We aim to find genes that add epigenetic marks to the DNA and understand how they co-operate at the molecular level to switch genes off. Our focus is on one such gene, SMCHD1. We are developing new drugs against SMCHD1 to treat incurable neurodevelopmental disorder PWS and muscular dystrophy FSHD.
6% of Australian men are infertile. Of these cases 50% are thought to be genetic in origin. Within this project we will replicate high-confidence genetic variants associated with human male infertility in the mouse. Doing so will allow the assignment of definitive genotype-phenotype correlations and the formulation of high confidence advice for clinicians and patients. It will also provide a means to define the mechanism of action and the tools for future pro-fertility treatments.
Defining The Genes That Dictate The Cellular Response To Tumour Protein TP53 Activation
Funder
National Health and Medical Research Council
Funding Amount
$784,896.00
Summary
The tumour suppressor TP53 prevents the growth of abnormal cells by activating processes such as cell death and irreversible growth arrest. A cell will undergo only one of these possible responses, but it is not known why some cells die and others only stop growing. We will use innovative methods to define the genes that dictate the cellular response to TP53 activation. This research has implications for cancer, as many therapeutics aim to permanently kill cancer cells by activating TP53.
Investigation Of The Molecular Basis Of Frailty And Development Of Frailty Biomarkers In A Novel Mouse Ageing Model
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Frailty is a state of high vulnerability for adverse health outcomes, and the prevalence of frailty increases with increasing age. There is very little known about why frailty develops, and there is also no widely accepted, efficient method of determining if someone is frail. This project will test blood markers for frailty, that will allow for optimization of treatment for older frail people and use mouse models of frailty to learn more about why frailty develops.
Asbestos-induced cancer is a big problem in the world. This Centre of Research Excellence application is to continue our highly successful National Centre for Asbestos Related Diseases, widely acknowledged as the world leader. We will ‘crack the cancer genetic code’, generate vaccines, discover better blood tests and new cancer imaging techniques and therapies. We will continue to train the next generation of researchers through our strong program and international collaborative network.