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.
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.
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.
Restoring Defective Protein Homeostasis In Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
Frontotemporal dementia (FTD) is associated with pathological accumulation and aggregation of toxic proteins in affected brain regions. This project will employ a novel high throughput drug screening platform technology, FTD patient-derived nerve cells and genetic mouse models to screen drugs to improve clearance of toxic proteins and nerve cell health. This approach should accelerate discovery of agents to potentially treat the underlying cause of FTD in an effort to slow disease progression.
Deciphering Mechanisms Of Disease Evolution In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$845,093.00
Summary
In many patients, cancers are ever-changing, even after they have formed. This explains why many cancers can spread beyond the point of cure by surgery and why they can become resistant to treatments. This project will use patient melanomas and laboratory modelling to understand how melanomas change as they grow and spread. The results will be used to identify the nature of evolutionary changes in cancer in order to predict and even exploit them in treatment.