Investigating the molecular mechanisms involved in the generation of new insulin-producing beta cells from stem/progenitor cells

Four year PhD studentship available
A four year PhD studentship is available in Rocio Sancho’s Laboratory, Centre for Stem and Regenerative Medicine, King’s College London investigating the molecular mechanisms involved in the generation of new insulin-producing beta cells from stem/progenitor cells.

Project Background
Diabetes is caused by the irreversible loss of insulin-producing beta cells in the pancreas. Recent research has revealed that the adult pancreas is capable of surprising cellular plasticity, opening new possibilities to reprogram adult stem/progenitor cells into insulin-producing cells (Bayens et al. 2014, Sancho et al. 2014; Ben-Othman et al. 2017). Three key transcription factors are sufficient to initiate a beta cell fate program when artificially introduced into adult stem/progenitor cells: Ngn3, Pdx1 and MafA. However, the tight regulation of these factors makes the process inefficient, and the beta cells generated are often not fully functional.

Project Summary
The main goal of the proposed PhD project is to delineate how the pro-endocrine factors Ngn3, Pdx1 and MafA are regulated in stem cells (both adult and iPS cells), to enable us to optimise the regulating pathways to improve the efficiency of beta cell generation and achieve fully functional beta cells. The PhD student will perform a genomic Crispr/Cas9-based screening to identify novel regulators of Ngn3/Pdx1/Mafa, and proteomics analysis to identify interactors of Ngn3/Pdx1/Mafa. The student will benefit of the state of the art technology within the CSCRM and in King’s core facilities (e.g. Genomics Centre, Proteomics, Nikon Imaging Center and Flow Cytometry & Cell Sorting Facility) to study the top screen hits in vitro. Once validated, functional assays will be performed to assess the physiological function of the newly generated beta cells. In vivo functional assays will be done in collaboration with Dr Nikolay Ninov in Technische Universität Dresden (TUD) and Professor Peter Jones/ Dr. Aileen King (King’s College London).

Timeline, Funding and Training
Starting in September 2017, the student will initially register as an MPhil student and transfer to PhD status following a successful upgrade meeting at 9 months. Studies in this thesis will be conducted as part of the International Research Training Programme (IRTG) on Immunological and Cellular Strategies in Metabolic Disease (ICSMD). This IRTG is a joint doctoral training programme between King’s College London (KCL) and the Technische Universitat Dresden (TUD). The successful student will conduct research relevant to the scientific mission of the IRTG, in collaboration with TUD. In addition to the Thesis Training Committee and Supervisors allocated at KCL, there will also be input into the project on a regular basis from expert(s) in TUD, and an expectation of collaborative work being conducted, including in Dresden. In the case of this project, it will be linked to the IRTG project theme “From stem cells to regeneration and cell replacement” and the TUD supervisor will be Dr Nikolay Ninov. In addition to thesis work, the student will benefit from a rich research culture at KCL including internal and external seminars, graduate school training opportunities and career development. The studentship will finish in September 2021.

Interested applicants should email Dr Rocio Sancho ([Email Address Removed]) their:
• Cover letter (explaining why you want to do this particular PhD).
• CV including the names of two referees, their email addresses and their relationship to you – preferably they have supervised you in a laboratory setting. Reference letters may be solicited prior to interview.

The closing date for applications will be 14:00, 26 May 2017.