Refining haematopoietic stem cell populations and their gene modification as a therapy for rare inherited disorders

Developments from academic and biotech sectors have driven gene and stem cell therapy to the clinical setting, with data demonstrating an encouraging long term safety profile and durable correction of several inherited genetic blood disorders such as ADA-SCID (Strimvelis) and X-CGD (OTL-102). Despite this progress, there is an urgent need to improve manufacturing processes for therapeutic gene modified cells in order to reduce the associated production costs, as this presents a major barrier to sustainability of access to patients. As production of sufficient quantities of viral vectors required to genetically modify a patients’ stem cells incurs the most significant costs, this studentship project will focus on approaches to reduce vector use, with an emphasis on identifying optimal therapeutic stem cells, and increasing their susceptibility to lentiviral transduction.

Specific aims
i) To identify a refined population of true long-term repopulating haematopoietic stem cells from within peripheral blood stem cells, which are capable of delivering a therapeutic effect, and evaluate clinically applicable methods for their isolation (Years 1 & 2, industry placement).
ii) To examine the efficiency of gene transfer to stem cell subsets using lentiviral vectors and apply targeted approaches to improve cell transduction (Years 2 & 3).
iii) To demonstrate the function and therapeutic potential of optimally transduced and selected stem cell subsets in a preclinical model of stem cell transplantation (Years 3 & 4).
Candidates will develop core laboratory skills in immunological, vector, gene transfer and cell biology techniques, in addition to working with directly translational research methods, using preclinical models and clinical grade platforms.

How to Apply
To apply to the MRC DTP iCASE Studentships visit our webpages (https://kcl-mrcdtp.com/icase-studentship-application-process/) to submit an online application via King’s Apply. Further information can be found on our ‘Frequently asked Questions’ pages (https://kcl-mrcdtp.com/icase-studentships-faq/).

Industrial Collaborative Awards in Science and Engineering (iCASE) Studentships
This PhD project is fully-funded PhD 4 year position available to start in October 2019, with the successful candidate joining the MRC Doctoral Training Partnership. They will start immediately on their PhD project in October 2019 and will participate in all other training and cohort activities of the MRC DTP.

About Us
The objective of our Doctoral Training Partnership (DTP - https://kcl-mrcdtp.com/) is to select motivated and curiosity-driven students and provide them with outstanding training, tailored flexibly to their individual needs and interests. We will equip them with the intellectual and technical skills that are needed for undertaking cutting-edge biomedical research and complement this with key transferable skills (including public engagement, business development and entrepreneurship) to ensure that they emerge as well-rounded scientists, prepared for their next career stage (whether in research or outside). Our excellent clinical setting will ensure all students benefit from an understanding of the context of medical research, helping develop scientists with a strong translational ethos.

Eligibility
https://kcl-mrcdtp.com/icase-studentships/
The MRC funding available supports Home/EU students within standard research council restrictions (http://www.legislation.gov.uk/uksi/2007/779/regulation/6/made). EU students are only eligible for a full studentship if they have lived, worked or studied within the UK for 3 years prior to the funding commencing. Unfortunately, we cannot accept applications from non-EU candidates.
https://mrc.ukri.org/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

If you have any questions, please get in touch with [Email Address Removed].

Applications Open: Monday 4th March
Application Deadline: Friday 5th April