Principal Supervisor name and department: Dr Ioannis Nezis, School of Life Sciences
PhD project title: Selective autophagy during ageing and neurodegeneration
Project description (max 500 words):
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 an evolutionarily conserved catabolic process that involves the
degradation of cytoplasmic material through the lysosomal pathway. It is a cellular response in
nutrient starvation but it is also responsible for the removal of aggregated proteins, damaged
organelles and developmental remodeling. Dysfunction in autophagy has been implicated in an
increasing number of diseases from bacterial and viral infections, to cancer and more recently, in
neurodegeneration and other ageing-related diseases.
Although it was initially believed that autophagy occurs randomly inside the cell, during the last years
there is growing evidence that sequestration and degradation of cytoplasmic material by autophagy
can be selective through receptor and adaptor proteins. To address the role of selective autophagy
during ageing and neurodegeneration, the fruit fly Drosophila Melanogaster will be used as a
genetically modifiable model organism. The aim of this project is identify novel selective autophagy
modulators in Drosophila, and to examine whether induced expression of autophagy and selective
autophagy adaptor proteins can rescue the disease phenotype in Drosophila models for human
neurodegenerative diseases and promote well-being.
Key experimental skills involved: basic cell and molecular biology, Drosophila genetics, confocal
microscopy and electron microscopy
References: He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of
autophagy. Annu Rev Genet. 43:67-93.
Contact details for application enquiries:
Dr. Ioannis P. Nezis
Associate Professor
School of Life Sciences
University of Warwick
Gibbet Hill Campus
Coventry CV4 7AL, UK
Phone: +44 (0) 24 76 150400
E-mail: I.Nezis@warwick.ac.uk
Keywords : Ageing, Autophagy, Drosophila, neurodegeneration