The Role Of Phosphorylation And Signalling For Invasion Of Plasmodium Falciparum Into Human Erythrocytes.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
The intracellular signals that govern Plasmodium falciparum malaria invasion of the red blood cell are poorly understood. It is likely calcium dependent phosphorylation leads to recruitment and activation of a cascade of proteins. This study combines a break-through in purification of viable P. falciparum merozoites with proteomic analysis of phosphorylation states to assess intracellular signalling. It is expected the processes identified will be unique to P. falciparum and targetable by drugs.
Role Of The Microglial Adaptor Molecule TYROBP In Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$469,433.00
Summary
Immune activation characterizes Alzheimer’s disease (AD) brains; however, how it impacts AD progression is not understood. Our previous studies in AD brains identified the immune molecule TYROBP, pointing at both beneficial and detrimental effects triggered by this molecule. Here, we aim to understand in detail how TYROBP is involved in AD and how we can enhance its beneficial effects and decrease its unintended actions.
A Sweet Therapeutic For Vascular Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$685,453.00
Summary
This project will advance a new drug to treat pregnant women diagnosed with the disease preeclampsia, and prevent them and their baby from becoming seriously ill. It will investigate how a novel sugar compound acts directly on the mother's blood vessels to restore normal vascular function, and provide the necessary preclinical proof-of-concept data to proceed to clinical trials.
The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There ar ....The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There are three different types of Siah protein in mice and this study investigates the function of the each protein by creating mice that lack one or more of these proteins. Our work to date has revealed that the Siah genes are involved in growth and fertility of mammals. The genes are also important for cell division, which implicates them in proliferative diseases such as cancer.Read moreRead less
Receptor Signalling Through Intracellular Calcium Stores In Chromaffin Cells
Funder
National Health and Medical Research Council
Funding Amount
$461,000.00
Summary
The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modi ....The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modified by hormones and transmitters and in how these complex calcium signals are used by cells to control their function. This project will investigate how hormones and transmitters can produce different types of calcium signals in nerve cells, and how these signals affect different aspects of the nerve cell's function. In particular, it will establish how two different types of specialised calcium stores within nerve cells are used by different classes of hormone and transmitter, and the distinct cellular functions these two calcium stores can regulate. The results will provide fundamental new information on how nerve cells control their activity and may help identify potential new targets for drugs.Read moreRead less
Regulation Of PtdIns(3,4)P2 Signalling By Inositol Polyphosphate 4-phosphatase-1
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
Normally cells only divide when they receive a stimulus such as from a hormone or growth factor. One of the signaling pathways which responds to growth factor stimulation is the PI3-kinase pathway. This pathway has been implicated in many different human cancers which occur when cells divide uncontrollably and invade into the surrounding tissues. We have idenitified a novel enzyme called the inositol polyphosphate 4-phosphatase that appears to regulate cell proliferation and differentiation.
Signalling To Telomeres: Mechanisms Of Action Of TGFb
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is contro ....Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is controlled by another protein called c-myc. This work will determine how telomerase is controlled by a balance between TGFb and c-myc in order to find ways to control telomerase and therefore cancer. We will use a combination of sophisticated techniques of cell molecular biology and biochemistry to pinpoint and target different molecules implicated in the actions of TGFb. This study will serve as an important baseline for more applied research in controlling ageing and cancer from development.Read moreRead less
I am a molecular-cell biologist studying the genetic regulation of intestinal homeostasis in development and disease with the aim of identifying novel molecular targets for the treatment of disease and that can be validated in relevant preclinical mouse models.
C-Cbl-directed Leukaemogenesis: The Roles Of Core-Binding Factors And PI 3-kinase Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$636,199.00
Summary
Myeloid leukaemia remains a major health problem with only about one third of patients being cured. More effective treatments are therefore needed. For these treatments to be developed more knowledge is required about the genetic and biochemical changes that cause myeloid leukaemia. This project aims to increase this knowledge by studying how cancer-causing proteins are involved in the development of myeloid leukaemia and how targeting these proteins can be used to develop new treatments.