Principal Supervisor name and department: Dr Ioannis Nezis, School of Life Sciences
Second Supervisor name and department: Professor Alfonso Jaramillo, School of Life Sciences
Where will the student be based? School of Life Sciences
PhD project title: Synthetic reprogramming of autophagy during ageing and neurodegeneration
Project description (max 500 words):
Autophagy is an evolutionarily conserved process where the cells degrade their own cellular
material. During autophagy, there is sequestration of cellular material into double-membrane
vesicles called autophagosomes. The autophagosomes fuse with lysosomes where the sequestered
cargoes are degraded by lysosomal hydrolases. The products of degradation are transported back
into the cytoplasm through lysosomal membrane permeases and can be reused by the cell.
Autophagy is implicated in tumor suppression and progression, neurodegeneration, myopathies,
lung and heart disease, diabetes, infections, and obesity. It is therefore very important to elucidate
the mechanisms of autophagy in normal and pathological conditions (1). 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 (2). The major aim of this project is to construct novel in vivo synthetically
controlled autophagic machinery using a combination of synthetic biology, cell biology, genetics and
bioinformatics. The main objectives of the project are:
1) To reengineer an autophagic machinery in Drosophila programmed against selected targets
in vivo.
2) To test whether the reengineered autophagic machinery can ameliorate disease-phenotypes
in Drosophila models of human neurodegenerative diseases
Key experimental skills involved:
 Molecular biology
 Drosophila genetics and cell biology
 Synthetic biology
 Confocal microscopy
References:
REFERENCES:
1) Yang Z, Klionsky DJ. (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol. 12:814-22.
2) Neufeld TP, Baehrecke EH. (2008) Eating on the fly: function and regulation of autophagy during
cell growth, survival and death in Drosophila. Autophagy 4:557-62.
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
Alfonso Jaramillo
Professor
School of Life Sciences
University of Warwick
Gibbet Hill Campus
Coventry CV4 7AL, UK
Phone: +44 (0)24 765 73432
Email: Alfonso.Jaramillo@warwick.ac.uk
Keywords: ageing, autophagy, protein aggregates, selective autophagy, synthetic biology