Mitochondrial protein quality control - Interaction of prohibitins with m-AAA proteases at the inner mitochondrial membrane
Protein quality control is an essential mechanism by which the cell ensures its viability and growth. Defects in protein quality control lead to the accumulation of damaged proteins, which plays a role in many diseases (e.g. cancer, diabetes, various neurodegenerative diseases) and ageing. This PhD studentship will be part of a larger project that aims to elucidate prohibitins’ role in premature cellular ageing by investigating how prohibitins interact with m-AAA proteases at a molecular level, and thus help to maintain healthy mitochondrial morphology and cellular metabolic capacity. Interactions between the proteins as well as their assembly in the membrane will be investigated using in-solution and soft matter techniques such as Small Angle Neutron and X-ray Scattering, lipid monolayer techniques, as well as biochemical assays. Data analysis with different pieces of software will be an important part of the PhD work.
Recombinant protein production and preparation will mainly be carried out in Dr. Anja Winter’s lab at the Department for Life Sciences, Keele University, but also in the labs of the Life Sciences group at Institut Laue-Langevin (ILL) in Grenoble, France. SANS measurements will be carried out at the ILL under supervision of Dr. Sylvain Prévost, using recombinantly expressed deuterated protein produced in the Deuteration Laboratory of ILL’s Life Sciences group. SAXS and X-ray crystallography will be carried out at ESRF, Grenoble, France and Diamond Light Source, Oxford, UK.
Keele University will be providing the stipend for the 1st year of the project, during which time the student will be mainly located at Keele University. In years 2 and 3 the studentship will be administered by ILL, and the student will be mainly located in ILL’s Life Science group, with strong links to the Large Scale Structure group established through the main ILL supervisor, Sylvain Prévost.
Applicants must be UK or EU nationals to be eligible for thestudentship. MSc in biochemical/ biophysical/ chemical
/natural sciences - minimum degree classification 2i orequivalent. An interest in both laboratory and
computational work (protein production and biophysicaltechniques) is essential - full training will be provided.
Applicants should provide a CV, personal statement and two referees.
Informal enquiries about the project should be made to the Project Leads [ Anja Winter ] [email protected]
and [Sylvain Prevost] and should include a CV and a personal statement.
Full applications including a personal statement to: http://www.keele.ac.uk/pgresearch/studentships/
Please quote FNS GS 2019-10 on your application.
The position will be based at Keele University for year 1 of 3 year period. For years 2 and 3 the student will be based full-time
at Institut Laue-Langevin (ILL) in Grenoble, France. Funding for year 1 at Research Council rates (2018/19 £14,777 per annum)
provided by Keele. For years 2 and 3 the student will be salaried at the ILL (salary €28,800 - from which tax and social charges are paid). For all three years 100% UK/EU tuition fees for 3 years commencing Academic year 2018/2019 will be covered by Keele. Funding for consumables and conference attendance available.
Arnold, I. and T. Langer, Membrane protein degradation by AAA proteases in mitochondria. Biochim Biophys Acta, 2002. 1592(1): p. 89-96.
Merkwirth, C. and T. Langer, Prohibitin function within mitochondria: essential roles for cell proliferation and cristae morphogenesis. Biochim Biophys Acta, 2009. 1793(1): p. 27-32.
Winter, A., O. Kamarainen, and A. Hofmann, Molecular modeling of prohibitin domains. Proteins, 2007. 68(1): p. 353-62.