Putting the brakes on ageing
Summary
We will investigate why damaged material accumulates in ageing cells and examine ways to stimulate the defence mechanisms of the cell.
Supervisor(s)
Research Location
Heart Research Institute, Camperdown, Sydney
Program Type
Masters/PHD
Synopsis
Background: The diseases of ageing represent one of the major health challenges this century. Despite their rapidly increasing incidence, our understanding of the underlying causes of many of these diseases is still limited. Ageing is characterized by a progressive accumulation of molecular damage to proteins, lipids and nucleic acids. The failure of the maintenance, repair and turnover pathways in ageing cells results in the accumulation of damaged material. Overview of Studies: Toxic free radicals are produced as a natural result of aerobic metabolism. Young cells and organisms can deal efficiently with the damage caused by these reactive species. In ageing cells oxidised proteins accumulate and can impair cell function. A key feature of our studies is the generation of ‘oxidised proteins’ in cells by the biosynthetic incorporation of oxidised amino acids. This is a novel approach we have developed. We will focus on the early stages of oxidised protein accumulation in cells to identify the initiating events. We will examine the mechanisms by which cells recognise damaged proteins and chaperone them to the proteolytic systems. We will investigate the phenomenon of ‘hormesis’ in which exposure to low levels of oxidative stress can protect the cells against otherwise harmful oxidants. Manipulation of these mechanisms could provide an alternative strategy for limiting the damaging effects of oxidised protein accumulation in ageing and in age-related diseases.
Additional Information
The techniques used in these studies will include HPLC, cell culture, real-time RT-PCR, microarray analysis, Western blotting, enzyme assays.
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Keywords
Ageing, degenerative diseases, oxidation, protein, proteolysis, Biochemistry, microarray, Chronic diseases & ageing, Human body
Opportunity ID
The opportunity ID for this research opportunity is: 183
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