Understanding The Activation Of Pro-apoptotic Bcl-2 Family Proteins For The Development Of Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$627,805.00
Summary
Programmed cell death is a process by which the body protects against rogue cells, eg cells potentially cancerous or infected by viruses. Dysregulation of the process occurs in cancer and can also lead to degenerative diseases. This work will discover the molecular mechanisms by which key proteins control the life/death switch in cells and will develop compounds capable of regulating their activity, setting the foundation for developing therapeutics aimed at regulating these processes.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
Structural Studies Of The Molecular Machinery Regulating Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Our bodies use a process called Programmed Cell Death to remove unwanted or dangerous cells. This work aims to understand the machinery that regulates this process at the molecular level. These insights will inform the development of drugs aimed at either initiating cell death when required, for example in cancer, or at inhibiting it when excessive cell death causes disease.
Structural Investigations Of The Bcl-2 Family Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
Programmed Cell Death is a process by which dangerous cells are removed from the body. Sometimes it goes wrong and causes disease, e.g. cancer cells stay alive when they should die. This project will study a group of proteins that regulate cell death, the Bcl-2 family of proteins, in order to understand the mechanism by which they control the balance of cell life and death. The findings will inform the development of new drugs aimed at regulating cell death in a variety of disease states.
The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a funct ....The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a functional, signalling role. The research will determine how these fibrils form and how the structures confers biological function. It could identify features in these fibrils that can be targeted as a means of ultimately preventing tissue damage after heart attack and stroke.Read moreRead less
Inhibiting protein-protein interactions involved in neural development and disease. This project will determine the molecular mechanisms by which the protein LMO4 (a regulator of brain development) binds to DEAF1 (which also regulates neural development) and CtIP (which protects against tumour formation). This will allow a set of reagents to be developed to help determine the functions of LMO4, and may ultimately be used to treat disease.
Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from c ....Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from cancer to heart disease. This project endeavours to advance our understanding of the proteins that interconnect autophagy and apoptosis. The results are expected to explain how cells determine their fate and inform future development of strategies to treat disease.Read moreRead less
Protein-protein interactions in the transcriptional regulation of neural development. Combinations of transcription factor protein regulate the expression of genes, but just how different combinations of these proteins specifically up or down regulate specific genes is poorly understood. This project will focus on the LIM-homeodomain transcription factors, which act in combination to form the so-called "LIM code" that specifies cell type specification during development. Using a series of biophy ....Protein-protein interactions in the transcriptional regulation of neural development. Combinations of transcription factor protein regulate the expression of genes, but just how different combinations of these proteins specifically up or down regulate specific genes is poorly understood. This project will focus on the LIM-homeodomain transcription factors, which act in combination to form the so-called "LIM code" that specifies cell type specification during development. Using a series of biophysical and structural approaches. This project will unravel the networks of protein-protein interactions that form the basis of the LIM code. This will help address a major issue in the field: How do interactions between transcription factors regulate DNA-binding specificity. Ultimately, this work may also lead to regeneration of nerve tissue.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100584
Funder
Australian Research Council
Funding Amount
$424,636.00
Summary
DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into ....DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into DNA damage. Insights into these processes will have the potential to improve preventative and therapeutic approaches to diseases such as cancer and neurodegeneration. Read moreRead less
Dissecting the mitochondrial pathway of apoptotic cell death. This research aims to identify each step in cell death regulation by the Bcl-2 family of proteins. Each step is a potential target for drugs that may help cancer cells die, or that may help normal cells such as heart and brain cells recover from damage.