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  • PhD studentship: Coenzyme Q10 a potential therapeutic target for ataxia: Evaluation of therapeutic strategies

PhD studentship: Coenzyme Q10 a potential therapeutic target for ataxia: Evaluation of therapeutic strategies

18 June 2014

Applications are invited for a PhD studentship at the Department of Molecular Neuroscience, UCL Institute of Neurology, and the Institute of Pharmaceutical Science, King’s College London. The supervisors for this project will be Dr. Iain P. Hargreaves, Dr. Jane Preston and Prof. Simon R.J. Heales.

The anticipated start date is 6th October 2014

Background:

Cerebellar ataxia is the most common clinical presentation of coenzyme Q10 (CoQ10) deficiency with 94 of 149 reported cases of this disorder presenting with this clinical phenotype. However, only 49% of patients with the cerebellar ataxic phenotype have been reported to demonstrate improvement/stabilisation in their ataxic symptoms following CoQ10 supplementation [1].

The reasons for the refractory nature of these neurological symptoms to CoQ10 supplementation remain unknown. However a major contributory factor may be the poor transfer of CoQ10 across the blood brain barrier (BBB) resulting in insufficient CoQ10 availability for the deficient neurons.

Project:

This study will assess the permeability of an in vitro human BBB model [2] to CoQ10 in comparison with other analogues of CoQ10, idebenone and duroquinone. A co-culture system of BBB and CoQ10 deficient neurons [3,4] will be established to evaluate neuronal uptake/intracellular distribution of CoQ10 following supplementation. This project will also evaluate the effect of CoQ10 supplementation upon mitochondrial electron transport chain function and cellular oxidative stress. A CoQ10 deficiency will also be induced in the BBB to assess the effect of this deficiency upon BBB permeability to CoQ10.

[1] Emmanuele V, Lopez LC, Berardo A, Naini A, Tadesse S, et al: Heterogeneity of coenzyme Q10 deficiency: patient study and literature review. Arch Neurol 2012; 69: 978-83.

[2] Patabendige A., Skinner RA., Morgan L., Abbott NJ. A detailed method for preparation of a functional and flexible blood–brain barrier model using porcine brain endothelial cells. Brain Res. 2013; 1521(100): 16–30.

[3] Duberley K, Abramov A, Chalasani A, Heales S J, S Rahman S, Hargreaves I P. Human neuronal coenzyme Q10 deficiency results in a global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and a reversal of ATP synthase activity: Implications for the pathogenesis and treatment. Inherit Metab Dis 2013; 36 (1): 63-73.

[4] Duberley KE, Heales SJ, Abramov AY, Chalasani A, Land JM, Rahman S, Hargreaves IP. Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells. Int J Biochem Cell Biol. 2014 May;50:60-3.

Environment:

The student will be integrated into the world leadings labs both at UCL and King`s College London. At UCL the student will be primarily supervised by Dr. Iain P. Hargreaves, and Dr. Jane Preston at Kings. The student will have the opportunity to attend UCL/Kings courses in relevant subject area, as well as interact with students and postdoctoral researchers from other departments.

Funding

The studentship is jointly funded for 3 years by a UCL Impact Studentship award co-funded by Ataxia UK, and will cover UK/EU university tuition fees and an annual stipend of £15, 863 (tax free).

Note all overseas candidates (i.e. non EU/UK) can only be considered if they provide formal proof, at the time, of a scholarship to fund the additional overseas tuition fees.

Person Specification

  • A first class or upper second class bachelor’s degree in biochemistry or a biological sciences subject (or equivalent EU/overseas degree), or a distinction or merit in a masters degree in biochemistry or a biological sciences subject.
  • An interest in mitochondrial energy metabolism and cell biology.
  • Experience of laboratory research, cell culture work and/or HPLC analysis preferred but not essential.
  • Good communication skills, both oral and written English.
  • A strong work ethic, with the ability to think creatively and work independently.

Duties and Responsibilities.

  • Establish BBB cell model under direction of Dr. Jane Preston.
  • Maintain accurate and up to date records.
  • Prepare progress reports and presentations on research as required.
  • Prepare manuscripts for submission to peer reviewed journals.
  • Travel for training, meetings or conferences.
  • Contribute to overall activities of the research team and departments as required.
  • Maintain an awareness and observation of Fire, and Health and Safety regulations at UCL and King`s. Actively follow UCL/King`s policies including Equal Opportunities and Race Equality policies.

Informal enquires

Please e-mail Dr. Iain P. Hargreaves for further information about the project (i.hargreaves@ucl.ac.uk).

Application is by CV and covering letter (including motivation for applying) e-mailed to ion.educationunit@ucl.ac.uk.

Closing Date: 18th August 2014, 5pm

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