To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that c ....To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that can kill tumour cells more effectively by directly triggering the normal death switch of the cell.Read moreRead less
Characterising The Beneficial Effects Of Estrogen On The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$594,722.00
Summary
Prostate cancer is hormonally regulated and currently managed by androgen ablation. This application seeks to study the potential benefits of estrogen action for the treatment of prostate disease, including PCa. We will show estrogen hormone action causes prostatic cell death, targeting the stem-progenitor cells so the treated prostatic tissue does not regenerate. This project will provide pre-clinical proof of the efficacy of estrogenic compounds as a potential therapy for prostate disease.
The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.
Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and ea ....Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and early dyschondroplastic lesions, in order to identify the sequence of molecular events leading to induction of disease. The basic understanding of joint development obtained from this work will assist in the development of strategies to prevent and diagnose dyschondroplasia in horses.Read moreRead less
Centre For Translational Pathology Research And Training
Funder
National Health and Medical Research Council
Funding Amount
$2,677,639.00
Summary
The Centre for Translational Pathology Research and Training is a collaborative network involving nine hospitals and research institutes affiliated with The University of Melbourne. It's goal is train a cadre of molecular pathologists experienced in collaborative multidisciplinary research who can effective translate research discoveries and inventions in to clinically useful diagnostic tests that will enable oncologists to individualise treatment decisions for patients with cancer, based on the ....The Centre for Translational Pathology Research and Training is a collaborative network involving nine hospitals and research institutes affiliated with The University of Melbourne. It's goal is train a cadre of molecular pathologists experienced in collaborative multidisciplinary research who can effective translate research discoveries and inventions in to clinically useful diagnostic tests that will enable oncologists to individualise treatment decisions for patients with cancer, based on the unique biology of the individual's tumour.Read moreRead less
The Effect Of Hepatic Pseudocapillarisation Of Old Age On The Disposition Of Chylomicron Remnants And Chylomicrons
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the li ....Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes have profound effects on the transport of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain in part the fact that old age is the major risk factor for many diseases and adverse drug reactions. In this study we are interested in the transfer of fats called chylomicron remnants from blood into the liver. Chylomicron remnants are lipoproteins rich in triglycerides that are produced after meals and broken down by the liver. In order to be metabolised, chylomicron remnants must pass through pores in the liver blood vessels called fenestrations. In old age, we have found that these fenestrations are reduced substantially, which will impair the uptake of chylomicron remnants by the liver, leading to marked increases in fat in the blood stream after meals. In this study, we will examine the effects of old age on the ability of the liver to metabolise chylomicron remnants, in particular focussing on the effects of the age-related loss of fenestrations on chylomicron remnant uptake. As well as providing an understanding of the crucial link between ageing and atherosclerosis, the studies will provide a potential new therapeutic target for the prevention of atherosclerosis in older people.Read moreRead less
All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these ....All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these components of the cytoskeleton are able to control the structure of cells. In addition, we have found that variants of these two components (called isoforms) are used to build structures in different parts of cells. This has led us to think about the anatomy of cells and tissues in a new way. In some ways its like building a city. You create different kinds of buildings to suit their purpose. Each building uses a combination of building blocks which suit the structural demands of rooms and the overall building. In this study, we are proposing to dissect out genes, or parts of genes, which supply specific types of building blocks. To do this, we plan to change these genes in mice and then examine the impact on cell and tissue anatomy. This promises to contribute to the conversion of anatomical science and pathology from descriptive to experimental-mechanistic disciplines.Read moreRead less