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Advances in modern medicine have led to a significant increase in human life expectancy. A consequence of this however, has been the increase of the frequency of age-related diseases and in particular, neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. Recent studies have indicated that dysfunction in autophagy has been implicated in neurodegeneration. Autophagy is the process by which a portion of the cytosol and organelles are sequestered by phagophores. The phagophore engulfs portions of the cytoplasm and forms a double-membrane-layered organelle called the autophagosome. The autophagosome can fuse with a lysosome and generate the autolysosome that has a single limiting membrane, where the sequestered material is degraded (Yang and Klionsky, 2010). The study of pathogenic human tissue is only giving very limited experimental possibilities. Therefore, model systems have to be used to study the functional aspects in neurodegenerative diseases and ageing in vivo.
To address the role of autophagy during ageing and neurodegeneration, the fruit fly Drosophila melanogaster will be used as a genetically modifiable model organism (Neufeld and Baehrecke, 2008). The first aim of this project is to develop molecular markers for monitoring autophagy in vivo and to examine their expression pattern during Drosophila neuronal development and ageing and in Drosophila models for human neurodegenerative diseases. With this approach we will try to uncover the involvement of autophagy during neurodegeneration and ageing in Drosophila. The second aim of this study is to identify the molecular mechanisms of autophagy in neurodegeneration and ageing. The major goal of this project is to obtain basic knowledge in the molecular details of the autophagic machinery that will facilitate the development of methods of treatment against neurodegenerative and ageing-related diseases.
Key experimental skills involved:
Basic cell and molecular biology; Drosophila genetics and cell biology; Confocal microscopy; Electron microscopy
Keywords: Ageing, Alzheimer’s disease, apoptosis, autophagy, Drosophila, Parkinson’s disease, neurodegeneration
Funding Notes:
The PhD will be funded by the School of Life Sciences, University of Warwick and will provide a stipend equivalent to UK Research Councils (at least £13,590 per annum) and Tuition fees at the UK/EU level paid in full.
Please see the School of Life Sciences webpage for more information about eligibility.
References:
Neufeld, T.P., and Baehrecke, E.H. 2008 Autophagy. 4:557-62.
Yang Z and Klionsky DJ. 2010 Nat Cell Biol. 9:814-822.
Research Assessment Exercise (RAE) 2008 Results