Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
The Role Of Intracellular Protein Trafficking In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is a progressive neurological disorder and is the most common cause of dementia. The development of therapies must be preceded by a thorough understanding of the molecular processes that underpin the disease. In this project we will examine the interactions between the Alzheimer’s precursor protein (APP) and the molecular machinery that controls its intracellular localization and breakdown to the toxic A? peptide that is central to disease pathology.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Innovative Use Of Hydrogel Technology To Recapitulate And Investigate Cardiac Pathology.
Funder
National Health and Medical Research Council
Funding Amount
$716,162.00
Summary
Hypertrophic cardiomyopathy is the leading cause of sudden death in the young. No treatment exists that can reverse or prevent it, primarily because the underlying mechanisms of the disease have not been fully elucidated. I will use innovative hydrogel technology to simulate the disease state. I will use this as a tool to identify the mechanisms involved with development of the disease. This will enable identification of potential therapeutic targets for prevention of the disease.
The Role Of Dynamin In Spermatogenesis, Sperm Maturation And Sperm-oocyte Interactions
Funder
National Health and Medical Research Council
Funding Amount
$551,950.00
Summary
Male infertility is an extremely common condition affecting 1 in 20 Australian men. One of the major reasons for this pathology is that the spermatozoa have lost their ability to interact with the egg and penetrate its outer vestments. In this project we shall investigate the role of dynamin in the regulation of these events. This research will provide new and powerful insights into the causes of male infertility, with practical implications for diagnosis and treatment of this condition.
In Vivo Analysis Of The Molecular And Neural Mechanism That Underly An Association Of MiRNAs With Mental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$593,778.00
Summary
Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor b ....Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor behavior in transgenic zebrafish.Read moreRead less
Protective Role Of The Depressor Arm Of The Renin-angiotensin System During Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$633,384.00
Summary
The motivation for unveiling the normal hormonal and molecular mechanisms involved in the extraordinary vasodilatation associated with pregnancy is that understanding these fundamental processes may provide novel insights into the pathophysiology of preeclampsia and intrauterine growth restriction, as well as potential therapeutic strategies for not only the treatment of these pregnancy specific conditions but also cardiovascular and renal diseases in non-pregnant women and men.
Investigation Of The Mechanisms Underpinning HSPA2 Dysfunction In The Spermatozoa Of Infertile Patients
Funder
National Health and Medical Research Council
Funding Amount
$481,563.00
Summary
Male infertility is an extremely common condition, that is frequently associated with the production of sperm that have lost their ability to recognize the egg. We have shown that this defect is frequently associated with a deficiency in a specific protein (HSPA2). By determining the mechanisms underpinning the loss of HSPA2, this project will provide powerful insights into the causes of male infertility, with practical implications for prevention, diagnosis and treatment of this condition.
Therapeutic Approaches To Circumvent NO• Resistance In The Type 2 Diabetic Heart And Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$563,337.00
Summary
Type 2 diabetes (T2D) is Australia’s fastest growing chronic disease, affecting almost 2 million Australians (who face poor cardiovascular health outcomes). We have discovered an exciting new avenue that may potentially more effectively counteract heart and blood vessel disorders in T2D patients in an acute cardiovascular emergency, of substantial clinical importance.