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.
This study aims to elucidate central pathways which can be manipulated to drive the storage of excess energy away from fat and instead directing it into the production of bone mass. Having identified leptin-responsive NPY neurons as important in the control of energy partitioning, we will focus on manipulating these neurons in the hypothalamus using innovative technology to alter body composition. This research has the potential to result in novel treatments for obesity and osteoporosis.
Identifying How The Enteric Nervous System Regulates Gut Permeability In Autism
Funder
National Health and Medical Research Council
Funding Amount
$448,643.00
Summary
This project aims to investigate causes of increased gut permeability in neurological disorders including autism and will apply neuroscience, immunological and microbiology techniques to clarify the causes of increased gut permeability in a well-characterised genetic mouse model of autism.
Harnessing The Dual Roles Of Pericytes To Improve Stroke Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$853,943.00
Summary
Pericytes are cells that are in the walls of capillaries - the smallest blood vessels. Pericytes control blood flow and help promote recovery after injury. In stroke, pericytes squeeze the capillary shut, limiting the amount of energy getting to the brain. This proposal will use innovative techniques to understand how pericytes limit blood flow and also how we can utilise pericytes to improve brain recovery after stroke. This will allow us to identify new potential treatment options for stroke.
Development Of An Intracellular Tau-specific Antibody Therapeutic For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$410,378.00
Summary
The protein, tau, is a promising therapeutic target for the treatment of Alzheimer's disease and related dementia's. Targeting tau is a challenge, however, as it is mostly localised within brain cells and a therapeutic must therefore be able to cross multiple barriers to engage and neutralise tau. This project overcomes this hurdle by using virus' to deliver a tau-specific antibody gene across the multiple barriers where it can be produced by brain cells and target intracellular tau.
Integrating Biology And Medicine To Develop 3D-structure Guided Drug Design For Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$978,832.00
Summary
Calcium channel inhibitors are commonly prescribed for the treatment of heart disorders such as angina, hypertension, arrhythmias and hypertrophic heart disease. This class of drugs is one of the leading causes of drug-related fatalities. The impediment to designing better drugs is a lack of understanding of the 3 dimensional (3D) structure of the calcium channel. We will enable for the first time a 3D structure blueprint for the design of safe and highly selective calcium channel therapeutics.
Characterisation Of Erusiolin - A New Peptide Hormone
Funder
National Health and Medical Research Council
Funding Amount
$547,202.00
Summary
Obesity and type II diabetes are epidemic diseases in Australia. Gut-derived hormones are key mediators in these diseases, due to their role in regulating appetite and blood glucose levels. Therapeutic modulation of these hormones also provides significant benefits for patients. In this proposal, we will determine the metabolic functions, such as appetite control, for a previously uncharacterised hormone, which is an unexplored therapeutic target for obesity and diabetes.
Investigating A New Regulator Of Cardiac Rhythm In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,704.00
Summary
Cardiac arrhythmias affect a high proportion of the population (2-5%) and can cause sudden death. Whilst the aetiology of arrhythmia can vary, there are clear genetic causes. Unfortunately, our knowledge of the genetic contributors is incomplete, hampering efforts to interpret genetic sequencing information. This project will undertake functional analyses of a novel arrhythmia gene and establish where, when and how it is required for correct cardiac rhythm.
A Cellular Identity Crisis: Deciphering How Mammary Epithelial Cells Form And Maintain Their Identity
Funder
National Health and Medical Research Council
Funding Amount
$843,826.00
Summary
The ability to regenerate human organs from adult cells efficiently and without error is a major goal of biomedical research in Australia, with significant economic benefits. As one of the most regenerative organs in a woman's body, the breast is an excellent model to study mechanisms that underpin tissue growth and regrowth. Moreover, as these pathways are often hijacked by cancer, this research has important implications for the development of new targeted therapies to treat breast cancer.
Oncogenic Determinants Of The Immune Response In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$588,144.00
Summary
There is an urgent need to develop new therapies for patients with AML. We have shown that the body's own immune system can target certain types of AML. We will determine how these types of AML change to escape control from the immune system and how this can be reversed to re-engage the anti-AML immune response. Using patient samples, we will determine how the anti-AML immune response changes during the course of standard therapy in order to best combine it with immune-targeted therapies.