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.
Proteins Involved In HIV Infection And Host Defense
Funder
National Health and Medical Research Council
Funding Amount
$323,244.00
Summary
I am a biochemist focused on answering the question: why is it that humans are susceptible to HIV infection, while certain monkeys are resistant? It is known that these monkeys have evolved proteins which can target and destroy the virus, but the equivalent human proteins don’t work against HIV. I intend to compare the monkey and human proteins to understand how the monkeys destroy the virus and why the human protein is defective. These studies will inform the next generation of HIV treatment.
Investigation Of Dendritic Cell Activation And Function In A Murine Model Of Plasmodium And Schistosoma Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$358,938.00
Summary
Malaria is responsible for over 2 million deaths annually, mainly in sub-Saharan Africa. Importantly, around 1 billion people in malaria endemic areas are infected with parasitic worms, thus malaria and worm co-infections frequently occur. This project will investigate how malaria and worm parasites interact to influence the immune response and clinical outcomes of each other in a mouse infection model. This will provide new strategies for the design of effective treatments in co-endemic areas.
The Regulation Of 14-3-3 Protein Function By Post-translational Modification
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
The cells of our body have control mechanisms that prevent them from growing abnormally. However, when cells become cancerous they escape the normal checks and controls and are able to survive, divide and grow uncontrollably. In the last decade the molecular basis of several of the control mechanisms involved in preventing cancerous growth have been uncovered. However, our understanding is far from complete and recent research reports suggest that we have thus far overlooked a whole level of reg ....The cells of our body have control mechanisms that prevent them from growing abnormally. However, when cells become cancerous they escape the normal checks and controls and are able to survive, divide and grow uncontrollably. In the last decade the molecular basis of several of the control mechanisms involved in preventing cancerous growth have been uncovered. However, our understanding is far from complete and recent research reports suggest that we have thus far overlooked a whole level of regulation of cell growth control. Signals that instruct a normal cell to divide are propogated by pathways of interacting molecules within the cell. These pathways are regulated by switch mechanisms that either modify the interacting molecules, thereby inactivating their activity or by controlling when and where the molecules are allowed to interact. This spatial and temporal control mechanism is mediated by a family of specialised molecules, called 14-3-3 proteins. Recent research indicates that the function of these 14-3-3 proteins is also tightly controlled, although as yet we don't understand how. This research proposal attempts to discover the molecular mechanism of regulation of 14-3-3 function. An understanding of this process may provide new molecular targets for the development of therapeutics against cancer.Read moreRead less
Insulin-regulated Aminopeptidase, Glucose And Memory
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
We have previously shown that inhibitors of IRAP improve performance in memory tasks in normal and memory impaired animals and are currently developing new treatments for memory loss using IRAP as a target. In this study, we will investigate the physiological roles of IRAP and its association with intracellular proteins. The knowledge obtained will provide insights of how the brain process memory and confirm the suitability of IRAP inhibitors as drugs for treating memory deficits.
The Role Of The EphA1 In The Normal Epithelial Organs And In Epithelial Tumour Progression.
Funder
National Health and Medical Research Council
Funding Amount
$564,500.00
Summary
The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in ....The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in the cells which form the skin, liver, kidneys, breast and prostate. These cells also form the lining of the mouth, stomach, bowel and lungs. Understanding how the EphA1 protein and other members of this family cooperate to control the development and maintenance of these organs will allow us to determine whether this protein might be involved in congenital defects and diseases in these organs (such as kidney failure, cirrhosis of the liver and skin diseases). A second main aim of this project is to explore further the observation that Eph proteins are abnormally highly expressed in a wide rangre of human cancers. This abnormal expression is directly correlated with the tumours spreading throughout the body. EphA1 is abnormally highly expressed in cancers of the bowel, lung, breast and prostate. These are the commonest cancers in man and some of the most difficult to treat. The work proposed asks how EphA1 contributes to the development and progression of these cancers. These results will have very direct implications for the development of therapies which target the EphA1 protein.Read moreRead less