Research Associate in Molecular and Genome Editing Therapeutics Group
The Dr. Jacków lab has an opportunity for a Postdoctoral Research Associate to join their Molecular and Genome Editing Therapeutics Group at King’s College London. The post, which is a FTE fixed term contract for 1 year (in the first instance with possibility for extension for 2 more years), will utilise cutaneous squamous cell carcinoma (cSCC) tissue from severe recessive dystrophic epidermolysis bullosa (RDEB) patients to investigate a molecular mechanism driving RDEB-cSCC development. RDEB is a currently incurable inherited skin disorder characterised by severe blistering of the skin. RDEB patients have a propensity to develop early and aggressive cSCCs, the current mechanism of which is not fully understood. Novel insights into this process could also help to explain wider cSCC formation.
This new postdoctoral position will build on previous work from the lab to better understand the mechanism of action of Ruxolitinib ( Jacków et al., JID 2021), an inhibitor that can reduce RDEB-cSCC tumor growth. We will use iPSCs reprogramming and differentiation technologies that our lab developed as a model to study RDEB-cSCC tumorigenesis ( Rami et al ., Int. J. Mol. Sci. 2021). The work will also dissect the relationship between the inflammatory/stromal microenvironments and RDEB-cSCC cancer progression.
The project will have access to skin biopsies from patients with RDEB-cSCCs from our clinic at the St John’s Institute of Dermatology, the largest tertiary referral Centre in the UK for RDEB. Advanced techniques such as single cell RNA sequencing, flow and mass cytometry, imaging mass cytometry and diagnostic histology will probe epithelial and inflammatory cells from patient cSCC tissue.
The project aims to profile how inflammation causes RDEB-cSCC development and progression through its interactions with the surrounding microenvironment and additionally explore the synergy of ruxolitinib inhibition with and without immunotherapy to achieve better control of tumour growth.
The post will be based on the Guy’s Campus within the School of Basic and Medical Biosciences at St John’s Institute of Dermatology. The candidate will work closely with the principal investigator Dr Joanna Jacków and support a collaboration with Dr James Arnold ( https://www.kcl.ac.uk/lsm/research/divisions/cancer/research/groups/tig). We will also closely work with Prof John McGrath and Prof Jemima Mellerio, both of whom are world-renowned experts in Epidermolysis Bullosa and will be the key clinical personnel to guide with RDEB patient selection and provision of samples. The postholder also will benefit more broadly from the vast interdisciplinary research and academic networks at King’s College London.
The successful candidate must have (or be about to receive) a PhD relating to cancer and/or Immunology. Candidates should be proficient in primary cell culture and phenotyping of cell subsets using flow cytometry. Experience with organoid culture and skills in bioinformatics analysis will be highly valued but not a prerequisite for this position. In addition, some experience in skin biology will be of benefit.
This post will be offered on a fixed-term contract for 1 year. This is a full-time post – 100% full time equivalent
- The day to day running of the project
- Isolate primary SCC, keratinocytes and fibroblasts from skin biopsies from patients with RDEB-cSCC
- Using induced pluripotent stem cells (iPSCs)reprograming and differentiation technologies
- Generation of RDEB-SCC-iPSC and RDEB-SCC-iKCs
- Using CRISPR-Cas9 technology to correct mutations
- Perform isolation of high-quality RNA from human cells and tissue and RT-PCR analysis.
- Work flexible hours as required by the experiments (e.g. being available for iPSCs cell culture and drug dosing at weekends)
- Work through close interactions with the clinical team supporting the project (Prof John McGrath and Prof Jemima Mellerio)
- Assists the Lab Head in managing the project
- Work closely and collegially with Dr James Arnold and his research group
- Contribute to general laboratory tasks
- Support other members of the group and contribute expertise to other projects within the Molecular and Genome Editing Therapeutics Group, as appropriate
- Contributions to writing of reports, grant applications, new patent applications and publications for appropriate scientific journals and present research findings at scientific meetings.
- Facilitate and maintain effective communication within immediate research group and with clinical and academic groups within the Institute/School
- Liaise regularly and effectively with clinical, research and admin colleagues within the Institute to ensure work is performed in accordance with Health and Safety and Human Tissue Act regulations
- Work effectively to specific deliverables and to strict deadlines
- Help with supervision of PhD students, placement students and junior staff.
- Trouble-shoot and optimize experimental protocols, including flow cytometry panels and cell culture protocols, iPSCs reprograming and differentiation methods
- Keep up with research developments in the field of Immunotherapy, Epidermolysis Bullosa and its cancer treatment options and apply knowledge to experimental interpretations
- Record, analyse and write up the results of experiments maintaining an up to date and comprehensible electronic record of laboratory work and store it securely.
- Prepare and present findings of research activity to colleagues for review purposes
- Present work and other material at laboratory meetings
- Present work and other material at meetings with collaborators as required
- Present research findings at scientific meetings as required
- Prepare progress reports on research for funding bodies as required
- Prepare data for and contribute to writing of manuscripts and grant applications as required
- Being an excellent team player able to work as part of an interdisciplinary team
- Always work in compliance with the Ethical regulations imposed by King’s College London, Guy’s and St Thomas’ NHS Trust and the
- Human Tissue Act.
- Always work in compliance with the Data Protection Act 1998.
- Carry out tasks that require the learning of certain skills
- Required to be aware of the risks in the laboratory and clinical work environment
The above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.
Skills, knowledge, and experience
- A PhD in a relevant area
- A good track record of research in a relevant area
- Research experience in a Tumour and/or Immunology and/or Inflammatory skin diseases-related project
- Experience using in vitro 2D and 3D models; ideally relating to cancer
- Experience with primary human samples (isolation and culture of cells from blood and tissues)
- To be competent in flow cytometry and its analysis
- Skilled in molecular biology techniques (PCR, RT-PCR)
- Experience in data analysis, including statistics
- With a track record of publication in high quality scientific journals
- Willing to work flexibly in accordance with the needs of the project to meet milestones
- Organised, highly motivated, able to take initiative in problem solving and working independently
- Experience in bioinformatic analysis of large datasets
- Experience with ethical approvals for human subjects
- To have a publication in a respected journal
*Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.
Interviews will be held remotely by the end of May and will include a 10 minute presentation of a previous research project that the applicant has conducted.
This post is subject to Occupational Health clearance.