UCL CONSORTIUM FOR MITOCHONDRIAL RESEARCH

PhD Studentship Position available

Deadline for applications is June the 6th 2012

Title

Targeting Mitophagy: The Activity Of Keap1 and Its Cell-Protecting Reversible Inhibitors

Supervisors

Dr Geoff Wells (UCL School of Pharmacy)

Dr Michelangelo Campanella (UCL CfMR and Royal Veterinary College)

Project

Preservation of the quality of cell components is essential to cellular homeostasis. ‘Autophagy’ - the process by which specific malfunctioning organelles are self-digested is crucial to this cellular 'quality control’. In particular, autophagy targeted to mitochondria, known as ‘mitophagy’, is paramount to ensuring proper mitochondrial function. Such processes are important because defective mitochondrial quality control, mediated by mitophagy, is linked to some types of neurodenerative disease including Parkinson’s Disease.

A number of natural products that interact with the protein Keap1 have broad cytoprotective activity including vascular and neuro-protective effects. These compounds have general effects on the cellular redox environment, in addition to specific activity relating to proteins involved in mitochondrial function.

Our aim is to develop a new series of Keap1 interactive small molecules that enhance the expression of antioxidant genes (including redoxins and glutathione synthesis and conjugating enzymes) and increase sequestosome-1/p62 protein (a crucial arbiter of autophagy and mitophagy) activity.

The project will focus on the development of new compounds with potent and selective activity and the detailed biological evaluation of their effects on mitophagy and related processes. The project will be multidisciplinary and span the interface between chemistry and biology.

Profile of the Candidate

We seek a talented applicant with a background in chemical biology, pharmaceutical sciences or a related disipline interested in contributing the pharmacology of a biological process at the basis of mitochondrial physiology. The practical training will span chemical synthesis through to detailed pharmacological and cell biological assays. This will enable the succesful candidate to develop a fundamental understanding of the science of mitophagy together with a solid knowledge of techniques involved in drug discovery, translational research.

Key References

1. Narendra, D. et al. J. Cell Biol. 2008, 183, 795-803; Jin, S-M. et al. J Cell Biol. 2010, 191, 933-942

2. Geisler, S. et al. Nat. Cell Biol. 2010, 12, 119-131

3. Hancock, R. et al. Free Radical Bio. Med. in press.

4. Seneviratne, M. et al. Curr Mol Med. 2012 May 1;12(4):476-82.

Applications forms and details about how to apply are available fromRegistry

The School of Pharmacy , University of London, 29/39 Brunswick Square , London WC1N 1AX

United Kingdom; E: phd@pharmacy.ac.uk; T: +44 (0) 207 753 5831

W: http://www.pharmacy.ac.uk/apply_phd.htm

--------------------------------------------------------

There is a faculty position advertised at University College London for a lectureship (a tenured position) in metabolism and metabolic disease. 

for details of the position please see 

http://www.jobs.ac.uk/job/AEF284/lecturer-in-metabolism-or-metabolic-diseases/

--------------------------------------------------------

Two 3 year studentships are available in the Duchen lab. Deadline for applications, Friday 16 March.

All enquiries to Professor Michael Duchen m.duchen@ucl.ac.uk, tel 020 7679 3207, to whom applicants should please send a CV and names and contact details of two referees.  A 2:1 or better is required according to UCL eligibility criteria. 

The students will join a lively group focused on various aspects of mitochondrial biology and cell signalling, as the core of the UCL consortium for mitochondrial research (UCL CfMR: http://www.ucl.ac.uk/mitochondria/)

Post One:

Eisai funded studentship: 'Defining the role of mitochondrial calcium uptake in cell life and death' in collaboration with Gyorgy Szabadkai (UCL) and Rosario Rizzuto (University of Padova, Italy). The work will explore the role of the newly discovered mitochondrial calcium uniporter in neuronal energy homeostasis and its specific role in glutamate induced cell death.  Work will primarily involve live cell imaging of primary neuronal cultures. 

Open to UK/EU citizens only

Funding for 3 years includes Tuition Fees and Stipend (Year 1: £23,188, Year 2: £23,652, Year 3: £24,125) References: 

1. Duchen MR, Szabadkai G. Essays Biochem. 2010;47:115-37.

2. Gandhi S.,…, Duchen MR, Abramov AY. Mol. Cell. 2009;33(5):627-38.

3. Abramov AY, Duchen MR, BBA 2008;1777(7-8):953-64.

4. De Stefani D… Rizzuto R. Nature 2011;476(7360):336-40.

Post Two:

Studentship jointly funded by the Muscular Dystrophy Campaign and the UCL Impact studentship scheme: ‘Mechanisms of mitochondrial dysfunction in the core myopathies’ in collaboration with Professor Francesco Muntoni (ICH).

The work explores the role of impaired calcium sigalling pathways in congenital muscle diseases, the core myopathies, which involve mutations affecting calcium signalling pathways of excitation contraction coupling and the impact of altered calcium signalling pathways on mitochondrial function. For the project, we will use human cells from patients with Central core disease available from the biobank of the MRC Centre for Neuromuscular Diseases and we also have a knockin transgenic mouse model available.  

Open to UK/EU citizens only

Funding for 3 years includes Tuition Fees and Stipend (Year 1: £15,980, Year 2: £16,380, Year 3: £16,790) 

References:  1. Duchen MR, Szabadkai G. Essays Biochem. 2010;47:115-37.

2. Brini M,.. MacLennan DH, Carafoli E. J. Biol. Chem. 2005;280(15):15380-9. 

-------------------------------------------------------

You may also wish to view the UCL vacancies website.