Structural And Biochemical Investigation Of The Bloom�s Complex, Defective In Bloom�s Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$184,661.00
Summary
Bloom�s Syndrome is a rare inherited disorder that results in greater than 90% risk of developing cancer by the age of 25. The gene that causes Bloom�s Syndrome, called BLM, protects cells from cancer-causing mutations hence affected individuals develop the same types of cancers as the general population, only much faster. We will investigate the properties of the BLM gene product and understand how it protects us from cancer, and may influence some forms of cancer treatment.
Understanding And Controlling PAS Domain Interactions In Basic Helix-loop-helix Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$599,918.00
Summary
We want to understand how particular proteins control the activity of genes that are a crucial part of the body's ability to respond to environmental stresses, such as low oxygen, seizure and environmental pollutants. The knowledge gained will help decipher the events that result in correct function in the cell, and the misregulation that leads to toxic outcomes and disease states. We will search for new compounds with potential application as therapeutics for cancer, heart disease and stroke.
Multi-domain Regulation Of DNA Damage Response Kinases
Funder
National Health and Medical Research Council
Funding Amount
$313,427.00
Summary
DNA damage plays a key role in the onset of cancer and the response to cancer therapies. Mutations in the Chk2 DNA damage response kinase are associated with increased cancer risk. We will study detailed mechanisms how phosphorylation of Chk2-like kinases contributes to normal copying of our DNA every time a cell divides, and how it regulates how Chk2 is activated. The studies will improve our understanding how cancer may originate and how cancer cells respond to chemo- or radiation therapy.
FHA Domain-dependent Functions Of Cell Cycle Checkpoint Kinases
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Human chromosomes as carriers of the genetic information are constantly subjected to DNA damage. This usually occurs spontaneously, simply as a result of oxidation of DNA residues as a byproduct of cellular energy consumption or as a result of errors during chromosome duplication in growing cells, and is compounded by chemical or physical agents, for example carcinogens, UV rays or X-rays. DNA damage can have severe consequences if not properly repaired, leading to genomic instability with loss ....Human chromosomes as carriers of the genetic information are constantly subjected to DNA damage. This usually occurs spontaneously, simply as a result of oxidation of DNA residues as a byproduct of cellular energy consumption or as a result of errors during chromosome duplication in growing cells, and is compounded by chemical or physical agents, for example carcinogens, UV rays or X-rays. DNA damage can have severe consequences if not properly repaired, leading to genomic instability with loss of vast tracts of DNA or inappropriate genome rearrangements, that may ultimately give rise to cancer. To prevent such dire consequences, all organisms from yeast to man contain molecular checkpoints that sense the presence of DNA damage and then activate a cellular response program that includes damage repair and prevention of cell division while damage persists. These molecular checkpoints are highly conserved throughout evolution which allows us to analyse the details involved in simple organisms such as yeast, to draw general conclusions on their function in more complex human cells. Along these lines, we are studying the function of two yeast proteins that are similar to the human Chk2 protein, a tumour suppressor that is mutated in a subset of families suffering from the Li-Fraumeni multi-cancer syndrome. We have identified new pathways by which these proteins contribute to the survival of cells after treatment with DNA damaging agents and will further charaterise these in the present proposal.Read moreRead less
Role Of FHA Domains As Protein-protein Interaction Modules In Cell Signalling
Funder
National Health and Medical Research Council
Funding Amount
$191,973.00
Summary
The proper processing of information in cells involves the association of different proteins to signalling complexes. We will decipher the role the so-called FHA module plays in the formation of protein complexes. FHA modules are present in several proteins that are important for the repair of damaged DNA and the stability of chromosomes. Understanding the structure and function of this module will be relevant for various forms of cancer where DNA is damaged.
A Single-stranded DNA Binding Protein Implicated In The Cellular Response To DNA Damage.
Funder
National Health and Medical Research Council
Funding Amount
$503,816.00
Summary
Humans have evolved multiple mechanisms to ensure the integrity of their genetic information, which is carried by DNA. Each cell suffers more than 100 000 insults a day to its DNA; therefore an effective DNA damage response is crucial for the maintenance of genetic integrity and for survival. This research proposal aims to explore the molecular actions of hSSB2, a newly discovered player in the cell's arsenal for repairing harmful DNA damage.
Molecular Mechanisms Of Disease In The Collagen VI-related Muscular Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
The inherited muscular dystrophies are an important cause of disability in Australia. This project concentrates on the second most common group of congenital muscular dystrophies - those caused by mutations in collagen VI and its interacting partners. We will determine how mutations affect the structure of the protein and how the muscle is disrupted by the mutations. This work will open the way for research into potential therapies. We will also find new genes that cause muscular dystrophy.
Dietary Protein-induced DNA Damage In Colon And Consequences For Colorectal Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$604,797.00
Summary
This research will explore the effects of dietary protein on genetic damage to cells lining the large bowel and risk of developing colorectal cancer. We will determine the degree and type of DNA damage resulting from increased protein, the cellular response to this DNA damage, whether it increases risk for developing bowel cancer and whether it can be minimised by other foods in both an animal model and humans.