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