The Bloomsbury Colleges | PhD Studentships | Studentships 2016 | Flirting in the little space: Homeostatic Regulation of the Mitochondria and Cytoskeleton Interplay via the Tubulin-Vdac-Tspo Pathway (RVC) & (Bbk)
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Flirting in the Little Space: Homeostatic Regulation of the Mitochondria and Cytoskeleton Interplay Via the Tubulin-Vdac-Tspo Pathway

Principle Supervisor: Dr Michelangelo Campanella (RVC)

Co-Supervisor: Professor Carolyn Moores

The overall aim of this studentship is to investigate the interplay between the microtubule and the mitochondrion by dissecting the interaction between Tubulin and the Voltage Dependent Anion Channel (VDAC) and its binding/regulatory molecule: the 18kDa Translocator Protein TSPO.

Mitochondria associate with the microtubules via which they move around the cells fulfilling their roles in energy provision and cell signalling (1). Recent literature has demonstrated that Tubulin –the most abundant of the cytoskeleton filaments- acts as a uniquely potent regulator of the VDAC which is the most abundant channel of the mitochondrial outer membrane of which constitutes the major pathway for metabolites exchange with the cytosol(3). TSPO, which is readily up-regulated under various pathological conditions, interacts and forms complexes with the VDAC via which signaling and regulatory transduction of core cellular events is influenced thus playing part in the mitochondrial and cellular homeostasis (4,5).

Nothing is known whether regulation of the VDAC by TSPO impacts the recruitment of free Tubulin on the channel and so the mitochondrial and cytoskeleton interplay. TSPO overexpressing cells do accumulate mitochondria that escape the quality control suggesting their movement on the cytoskeleton could be impaired as it is their function (4,5).

Via this studentship project we shall address whether and to what extent the molecular and pharmacological regulation of TSPO influences the interplay between VDAC and Tubulin. This endouver will be achieved by adopting  a combined and balanced experimental work based on cutting edge approaches of biochemistry, structural and molecular biology and pharmaco-functional assay.

This project will therefore inform on aspects of biology little explored despite the relevance these may have in unveiling how eukaryotic cells adapt to pathological cues, developing and ageing conditions.

It will do so by providing an attractive and competitive training opportunity for a student desired to be formed in the principles and applications of molecular cell biology, in vitro pharmacology, biochemistry and structural biology.

Candidate Requirement:

 

Key References:

  1. William M. Saxton, Peter J. Hollenbeck. The axonal transport of mitochondria J Cell Sci 2012 125: 2095-2104; doi: 10.1242/jcs.053850
  2. Nicol Birsa, Rosalind Norkett, Nathalie Higgs, Guillermo Lopez-Domenech, Josef T. Kittler. Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins. Biochemical Society Transactions Dec 2013, 41 (6) 1525-1531; DOI: 10.1042/BST20130234
  3. Rostovtseva TK, Sheldon KL, Hassanzadeh E, Monge C, Saks V, Bezrukov SM, Sackett DL. Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration.Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18746-51. doi: 10.1073/pnas.0806303105. Epub 2008 Nov 24.
  4. Gatliff J, East D, Crosby J, Abeti R, Harvey R, Craigen W, Parker P, Campanella M. TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy. 2014;10(12):2279-96. doi: 10.4161/15548627.2014.991665.
  5. Gatliff J and Campanella M. TSPO: kaleidoscopic 18kDa amid biochemical pharmacology, control and targeting of mitochondria. Biochemical Journal in press.

Further details about the project may be obtained from:

Principle Supervisor: Dr Michelangelo Campanella (mcampanella@rvc.ac.uk)

Co-Supervisor: Professor Carolyn Moores (c.moores@mail.cryst.bbk.ac.uk)

Further information about PhDs at the Royal Veterinary College is available from:

http://www.rvc.ac.uk/study/postgraduate or by e-mail researchdegrees@rvc.ac.uk

Application forms and details about how to apply are available from:

http://www.rvc.ac.uk/study/postgraduate/phd/how-to-apply

Closing date for applications is:

Sunday 17th April 2016