The Bcl-2 Life/death Switch - Why Do Some Bcl-2 Proteins Kill Cells Whilst Others Promote Their Survival?
Funder
National Health and Medical Research Council
Funding Amount
$375,510.00
Summary
The cells of all animals possess the ability to commit suicide. When this natural process of cell death is dysfunctional, diseases such as cancer arise. Our aim is to understand the molecular mechanisms that underlie this process by providing atomic resolution snapshots of key components of the cell death machinery. By understanding the fine details of cell death regulation we can develop new drugs that target and kill rogue cells such as those found in tumours.
Focus On Molecular Mechanisms By Which Cells Kill Themselves.
Funder
National Health and Medical Research Council
Funding Amount
$4,366,120.00
Summary
The main aim of this Fellowship is to enable me to further expand, enhance, and strengthen the study of cell death at La Trobe. I wish to establish a centre for bio-medical research at La Trobe that acts collaboratively with local, national and international researchers to conduct basic research and harness the results to develop new therapies. Since moving to La Trobe in January 2006 I have been able to build and expand the critical mass of cell death researchers by recruiting laboratory heads, ....The main aim of this Fellowship is to enable me to further expand, enhance, and strengthen the study of cell death at La Trobe. I wish to establish a centre for bio-medical research at La Trobe that acts collaboratively with local, national and international researchers to conduct basic research and harness the results to develop new therapies. Since moving to La Trobe in January 2006 I have been able to build and expand the critical mass of cell death researchers by recruiting laboratory heads, post-doctoral fellows and several PhD and Honours students. These have joined post-docs, who moved with me from WEHI. We continue to have very close links with the WEHI Cell Death NHMRC Program Grant I remain a Chief Investigator on that grant, renewed in 2006. Because many of the WEHI facilities are on the La Trobe campus at Bundoora, my lab has better access to new mouse strains, monoclonal antibody production, medicinal chemistry, and genetically modified mouse production than those at WEHI in Parkville. This Fellowship will allow me to accelerate the building of a research group that will make substantial collaborative contributions to the basic scientific study of the mechanisms of cell death, to identification of therapeutic targets, to testing and validation of novel pharmaceutical compounds in vitro, and to facilitate clinical trials in Australia. Australian research on the basic mechanisms of cell death is not just of international standard, it is world leading. While it is important that our research is funded to maintain this position, we do not see ourselves as competing with overseas groups, but participating in a joint scientific effort. The translation of basic findings into new treatments will require the input from pharmaceutical industry that Australia lacks. To shorten the time for clinical translation, and to benefit from these developments, we must retain our research credentials, and remain collaboratively integrated with the international effort.Read moreRead less
Cancers arise as a result of the impairment of critical cellular processes following the mutation of important regulatory genes. I am a molecular biologist and I study how the proteins of the Bcl-2 family regulate apoptosis, a process of cell death essential to maintain homeostasis in multicellular organisms, with the aim of designing drugs to kill cancer cells selectively. I am also interested in discovering new genes involved in the development of cancer using new genomics technology.
Deciphering Activation Of The Apoptotic Cell Death Program
Funder
National Health and Medical Research Council
Funding Amount
$577,109.00
Summary
Apoptosis is the cell death mechanism by which unwanted, damaged or excess cells are removed from the body. It is critical for normal development and immune system function, and is deregulated in a number of diseases including cancer, neurodegeneration and autoimmunity. We shall determine how apoptosis is controlled by a family of proteins called the Bcl-2 family, thereby providing insight for the development of novel therapies.
The balance between cellular survival and death must be tightly regulated. Cells respond to viral infection by self-destructing, thus limiting viral spread to other cells. Viruses have evolved ways to subvert this defensive cell suicide. This project will define and characterise viral factors that maintain host cell survival during infection. These may be targets for the development of new anti-viral therapies and vaccines.
Developing A New Treatment Method To Prevent Lymphopenia Associated With Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$435,939.00
Summary
Sepsis or blood poisoning kills more people than breast cancer, prostate cancer and HIV/AIDS combined. It has a huge economic burden, yet there is no proper diagnostics markers or treatment. One of the main reasons for sepsis-mediated mortality is lack of functioning immune system patients. We have been able to elucidate the molecular mechanism of sepsis-mediated immune cell death and through this project, we aim to develop diagnostics and therapy for treating sepsis-mediated immune suppression.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
Cell death is a normal process that permits the growth and defense of our vital tissues. One kind of cell death, necroptosis, is characterised by the swelling and bursting of cells, triggering inflammation. Necroptosis is a key feature of illnesses ranging from colitis to arthritis, and contributes to the brain and heart damage that follows strokes and heart attacks. Understanding necroptotic cell death will pave the way for new therapies for those who suffer from these devastating conditions.
Understanding how Plasmepsin V directs export of malaria virulence proteins to the host cell. This project aims to characterise how malaria parasites survive and manipulate infected host cells by exporting virulence proteins. This project may identify essential proteins that allow the malaria parasite to transform the host in order to survive, replicate and hide from the immune system and provide new data on protein export in liver-stages.