Principal Supervisor: Dr Ioannis Nezis, School of Life Sciences
PhD project title: Autophagy during cardiac ageing
Project description:
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). Cardiac ageing is the
progressive decline of heart function. It contributes to increased cardiovascular mortality in elderly
humans, and because human lifespan is continuously rising, mortality associated with heart disease
is dramatically increasing. It is therefore critical to understand the mechanisms of cardiac ageing.
However, studying the mechanisms of cardiac ageing in mammals has limitations. First, heart
function is absolutely critical for mammalian viability. Second, the long life span of mammals makes
them impractical for studying the genetics of ageing. To address the role of autophagy during cardiac
ageing we will use the fruit fly Drosophila melanogaster as an excellent genetically tractable model
organism. Interestingly, many genes controlling heart development have been shown to be
conserved from flies to mammals (2). The aims of the project are:
1) To elucidate the role of autophagy during normal cardiac ageing in Drosophila.
2) To test whether induced expression of autophagy in Drosophila adult heart can promote
resistance to stress and prolong life span
3) To examine whether selective autophagy of protein aggregates or damaged organelles
ameliorates age-related cardiac dysfunction.
Key experimental skills involved:
 Basic cell and molecular biology
 Drosophila genetics and cell biology
 Confocal microscopy
 Electron microscopy
References:
REFERENCES: 1) He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of
autophagy. Annu Rev Genet. 43:67-93.
2) Bier E, Bodmer R (2004) Drosophila, an emerging model for cardiac disease. Gene. 342:1-11.
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
BBSRC Remit area: Molecular systems biology (including Gene expression, Clock systems,
Molecular mechanisms, and Neurosciences)
Keywords: ageing, autophagy, heart, protein aggregates, selective autophagy
Please state below which hazards may be connected with this studentship:
The studentship will entail work involving:
Chemicals – high toxicity and category 1 or 2 substances
Organo-phosphate or carbamate pesticides
Skin or respiratory sensitising agents (e.g. insect parts, organic
dusts from animals, spores, pollen, antibiotics, fibres, chemical
sensitisers, wood dust etc)
Radionuclides
Significant manual handling
Mechanical repetition where the frequency and duration are
significant
Working in areas where there are temperature extremes
Driving vehicles (tractors, fork lifts, ATVs etc)
Crop planting, harvesting, recording or grading
Working in close proximity to bees or other stinging insects
Working at height [>2 m] (using various types of access
equipment)
Working with noisy or vibrating equipment
Working at night (between 11.00pm and 6.00am)
Food handling
Other significant hazards (specify)
Research Areas
√ if applies
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Approved by Head of School or representative: YES/NO
Comments if not approved:
Name:…Ioannis Nezis………………… Signature:…
Date:…23 October 2012………
………………………………