Investigation Of The Role Of The ATM Protein In Peroxisome Function And Biogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$250,756.00
Summary
Ataxia-telangiectasia (A-T) is a complex multisystem disease characterized by extreme sensitivity to ionizing radiation (X-rays) and susceptibility to cancer, however the most debilitating symptoms are neurodegeneration and susceptibility to bronchial infections. The gene (atm) which is mutated in this disease has recently been cloned and current research is focussed on the function of the protein (termed ATM) that this gene encodes. We have localized the ATM protein to the nucleus, where it pla ....Ataxia-telangiectasia (A-T) is a complex multisystem disease characterized by extreme sensitivity to ionizing radiation (X-rays) and susceptibility to cancer, however the most debilitating symptoms are neurodegeneration and susceptibility to bronchial infections. The gene (atm) which is mutated in this disease has recently been cloned and current research is focussed on the function of the protein (termed ATM) that this gene encodes. We have localized the ATM protein to the nucleus, where it plays a role in monitoring DNA damage, and also to vesicles in the cytoplasm of the cell. We have demonstrated that some of these vesicles are peroxisomes, vital cellular organelles involved in a wide range of metabolic functions. The importance of peroxisomes is evidenced by the severe abnormalities in patients with disorders of peroxisome formation and function. Interestingly many of the neurological features of these patients overlap with those displayed by A-T patients. We propose that abnormalities in peroxisomal function in A-T may contribute to the development of neurological symptoms and we plan to examine the function of peroxisomes in cells from A-T patients, and in tissues from A-T mutant mice. This work may help design new treatments to ameliorate the most debilitating aspects of this disease.Read moreRead less
The Organisation Of The Chromosome Into Distinct Epigenetic Domains And Its Link With Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,591.00
Summary
This investigation will show that a key cellular mechanism that determines how the chromosome is organised into stable domains is by changing the make-up of chromosomal domains through the replacement of histone proteins with specialised forms of histones called variants . This fundamental research will provide important new information on how chromosomes become unstable in cancer.
Regulation Of The Histone Code By Histone Variants
Funder
National Health and Medical Research Council
Funding Amount
$589,425.00
Summary
A fundamental unanswered question in biology is how a single fertilized mammalian cell can differentiate into a multicellular organism when every differentiated cell type inherits the same DNA. Fundamental to this development process is that different sets of genes are expressed in different cell types. This investigation will show that a key mechanism to regulate gene expression is the way our DNA is covered with specifically modified and altered forms of histone proteins.
Genome Maintenance And HSSB1, A Novel Player In The DNA Damage Response Pathway
Funder
National Health and Medical Research Council
Funding Amount
$646,822.00
Summary
We propose to characterize a novel player in the DNA damage response pathway. This study is expected to pave the way for the possible treatment of diseases that are caused by a nonfunctioning damage response pathway. There is an international effort to identify new proteins involved in this pathway and the funding of this proposal will provide leadership in Australia.
Alzheimer's disease is the most common form of dementia and is the fourth biggest killer in developed countries. This proposal concerns the biochemical investigation of a protein implicated in Alzheimer's disease. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide an understanding of what the protein's normal function is in the body and may form the basis for the design of drugs to combat the disease.
Defining Mechanisms Of Follistatin-mediated Muscle Adaptation, For Treatment Of Frailty And Muscle-related Diseases
Funder
National Health and Medical Research Council
Funding Amount
$557,478.00
Summary
Physical frailty-weakness is one of the most common symptoms of serious illness and a key cause of death. I propose to study a new model of skeletal muscle growth, to learn more about the causes of wasting in muscle-related diseases. The work will identify cell mechanisms that cause loss of muscle strength, and will help develop novel treatment approaches to prevent or reverse physical frailty in illness. New therapies to combat frailty are vital to improve the health of our community.