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Graduate Studentships

 PhD studentship/Early Stage Researcher (ESR) - TRANSMIT - TRANSlating the role of Mitochondria in Tumorigenesis

As part of the Horizon 2020 project TRANSMIT, the Frezza lab at the MRC Cancer Unit has an opening for an ESR for 36 months. The  laboratory focuses on understanding the role of the mitochondrial enzyme and component of the tricarboxylic acid (TCA) cycle Fumarate Hydratase in tumorigenesis. The group has recently demonstrated that fumarate, accumulation in FH-deficient cells, elicits a powerful epigenetic reprogramming that leads to the suppression of miRNA200, and induction of epithelial–to-mesenchymal transition (Sciacovelli et al, Nature 2016). This epigenetic and phenotypic switch makes FH-deficient cells more motile and invasive, predisposing to metastasis. Although it has been demonstrated that fumarate has a role as epigenetic modifier, its effects on chromatin structure and function are still unknown. The avertised project will help to elucidate the link between TCA cycle dysfunction, accumulation of fumarate, and downstream epigenetic changes involved in tumorigenesis. To this aim the ESR will investigate the hypothesis that fumarate controls the activity of histone and DNA demethylases involved in DNA and histone methylation, causing broad epigenetic changes. The ESR will first generate a 3D cellular model of FH-deficiency by deleting FH in human renal cell lines obtained using CRISPR technology. He/she will then perform comprehensive subcellular metabolomics analyses to study the metabolic changes induced by the loss of FH in a compartment-specific manner, focusing in particular on the accumulation of fumarate in the nucleus. Then, the ESR will perform an extensive epigenetic analysis aimed at understanding how fumarate modulates genes expression and chromatin structure by altering DNA methylation and histone marks deposition. To assess DNA methylation, genome scale bisulfite sequencing and liquid chromatography analyses will be performed. Further, ESR will also perform Chip-bisulfite sequencing analyses to evaluate changes in histones binding to chromatin and their association to methylated DNA. These epigenetic changes will be merged with RNA-seq experiments to find the link between epigenetic modification and gene expression.

Subject area of PhD program in which the ESR will be enrolled and PhD program duration: 3-year enrollment to a PhD Medical Science, University of Cambridge

PhD program starting date: 01/10/2017

Required Educational Level

Degree: Applicants should hold a Masters level Degree in Biological Sciences in the field of Biochemistry, Cell Biology, Cancer Biology.

Skills: The ideal candidate should be familiar with the field of cancer metabolism and have a clear understanding of cellular metabolism and mitochondrial physiology. He/she will have proven experience with cell culture and several lab techniques, including western blotting, molecular biology. The ideal candidate should also be familiar with the basics bioinformatics tools and be familiar with software for data analysis. A distinct advantage will be previous experience with metabolomics experiments and work in the field of caner metabolism, and familiarity with epigenetics.

Additional requirements: Team spirit, good communication skills, and trans-national mobility

Languages: English

Eligibility: The applicants must be in possession of a degree in Biological sciences at the date of recruitment - an ‘early stage researcher’ (i.e. in the first four years of his/her research career and not have a doctoral degree). The applicants must not have resided in the country where the research training activities take place for more than 12 months in the 3 years immediately prior to the recruitment date and not have carried out their main activity (work, studies, etc.) in that country.

The applicant may be a national of a Member State, of an Associated Country or of any other Third Country.

Benefits

  • Enrollment in a PhD school in Medical Science
  • A highly multidisciplinary, cross-cultural and competitive training program in the field of metabolism in cancer
  • Secondments and a specific training program
  • Vacation days/year: 33 days + bank holidays
  • 3-year employment contract: The successful applicant will receive the full Marie Sklodowska-Curie Early Stage Researcher allowances as set by the European Commission: €52,095 per annum before employer costs (indicative £ sum: £33,248 per annum gross salary, using estimated £:€ rate of 1.22, after employer costs deducted).  Additional annual allowance available for eligible fellows with family dependents: €6,000 before employer costs.

Selection criteria

Applications, in English, should include a CV, a covering letter, detailed academic transcripts, a copy of the master’s thesis and a letter of reference - all to be submitted by email to Christine Fox (cf208@MRC-CU.cam.ac.uk)

First selection step: Curriculum evaluation. Numerical scores will be awarded for various grading criteria such as study marks obtained, duration of study, scientific publications in peer reviewed journals, reference letters. Only those candidates who are shortlisted from this step will be contacted by e-mail for the second selection step.

Second selection step: Skype or face-to-face interviews in which candidates will be required to give a short presentation of their master’s thesis and to discuss a scientific paper that they will receive three weeks before the interview. The interview panel will include the principal investigator and other members of the host laboratory.

 

Application deadline: 30th April, 2017

For further information and to apply online for this vacancy go to: http://www.jobs.cam.ac.uk/job/13193/

 


 

 

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