Job description

Background
The postholder will be a key researcher in an MRC-funded project to study the mechanisms of response and resistance to novel epigenetic therapies in Acute Myeloid Leukaemia (AML). This position will be supervised by Dr Lynn Quek, based in King's College London's Denmark Hill Campus.
AML is an aggressive bone marrow cancer which is incurable in the majority of patients. Our focus is to improve our understanding this disease with an ultimate aim to translate this knowledge to better treatments for patients. The focus of our research is to better understand the biology of leukaemia propagating cells in patient-derived AML which are mutated in isocitrate dehydrogenase (IDH) 1 and 2 genes. This important group of AMLs account for 20-30% of all AMLs.
Inhibitors of mutant IDH enzymes such as Ivosidenib and Enasidenib have recently been developed and FDA-approved to treat IDH-mutant AML. We have shown that IDH inhibitors restore blood function in AML patients by inducing differentiation of leukaemic cells previously unable to differentiate normally into mature blood cells (Amatangelo et al. Blood, 2017). We recently described the clonal dynamics of response and resistance to IDH inhibitor therapy in patients and demonstrated the impact of clonal heterogeneity on the function of AML cells in vivo (Quek et al. Nature Medicine, 2018).
We are looking for an ambitious research scientist with excellent computational skills and experience, who takes pride in performing scientific work to high technical standards. The successful candidate will have excellent organisation skills, who can demonstrate that (s)he is ready to take on new challenges. This postholder will be a key member of a team to study the metabolic and epigenetic events which underlie cell fate decisions in human patient IDH-mutant AML cells treated with IDH inhibitors, and be involved in analysis of clinical trial data.
This work requires expertise in analysis NGS data including WES, bulk and single cell RNA-seq and single cell ATAC-seq. Knowledge of methylation-seq would be an advantage. Previous experience of medical statistics and analysis of clinical data is desirable. The candidate should have a good understanding of laboratory techniques used to study haematopoiesis and leukaemia, including multi-omics and flow cytometry. The postholder will be expected to be self-driven in developing new skills. The postholder may be asked to co-supervise junior members of team and provide training in computational methods.
We are able to offer wider support and networking with computational teams within our network of collaborative research groups within KCL.
The successful candidate will have a good track record in Haematology research, demonstrate self-motivation, independent critical thinking, flexibility and good teamwork. This post will be ideal for a computational scientist who has a background in Clinical Haemato-oncology, especially in myeloid malignancies and allogeneic stem cell transplantation. There may be opportunities for additional clinical work that would attract additional clinical pay supplements (e.g. supporting outpatient clinics and clinical trials activity) for the suitably qualified individual.
Dr Quek is especially interested in helping promising researchers develop their career and will suit an early career clinical academic looking for post-doctoral experience prior to application for a post-doctoral intermediate research fellowship. This project will provide excellent scientific training, working in an area that has direct relevance to patient care.

This post will be offered as a full-time, fixed term contract for 24 months.

Key responsibilities

• Motivation to perform research to the highest standards, aiming for publication in high impact scientific journals
• Management of own academic research and administrative duties, planning, developing and executing experiments in discussion with Dr Quek. This involves project management, to co-ordinate multiple aspects of work to meet deadlines
• Contribute directly to scientific discussions with Dr Quek and other members of the group and collaborators
• Be able to adapt and develop new experimental approaches
• Coordination and running of the laboratory including supervisory responsibilities for laboratory staff and students
• Work as part of a team to prepare documentation e.g. grant applications, manuscripts for publication, scientific meetings; attend scientific meetings to present data
• Be a source of information and advice to other members of the group on computational and statistical methods.
• Ability to work flexibility to accommodate needs of the research programme.
• Undertaking other duties as may be that are commensurate with the grade and responsibilities of the post.

Technical expertise required for this post include:

• Computational analysis of genomic, transcriptomic, methylation and ATAC-seq data sets
• Adapting and developing novel computational tools and pipelines
• Statistical analysis of clinical data, including clinical trials
• Management of large data storage, including liaison with
• Data collection and analysis, preparation of formal reports in a timely manner, maintain clear laboratory/ database records
• Follow the KCL safety guidelines and adhere to risk assessments and COSHH regulations concerning the handling of chemical and biological substances

Communication & Networking: the postholder will

• Collaborate within King's College London and with collaborating centres, necessary for successful completion of the project. This will require prompt responses to work-related emails, and participation in teleconferences and in face-to-face meetings.
• Communicate conceptual and complex ideas to a variety of audiences using appropriate media and methods.

Decision Making, Planning & Problem Solving: the postholder will

• Be responsible for day-to-day decisions to ensure smooth running of the project and will be expected to discuss experimental plans with Dr Quek.
• Work independently in planning day to day activities in accordance with the project deadlines as agreed with Dr Quek.
• Be able devise and trouble-shoot work flows

Analysis & Research: the postholder will

• Work towards delivering agreed project goals.
• Give support to junior team members in dealing with queries and monitor objectives and standards
• Write or contribute to publications or disseminate research findings using other appropriate media.
• Make presentations at conferences or exhibit work in other appropriate events.

Teamwork & personal development: the postholder will

• be expected to collaborate and liaise with external collaborators.
• Be expected to supervise team members
• Act as a responsible team member, leading where agreed, and develop productive working relationships with others.
• Be self-motivated to improve their skills and knowledge, and keep up to date with developments in the field

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

Essential criteria

• PhD or MD in relevant area of Medicine, Cellular/ Molecular Biology or Biochemistry (or applicant should provide evidence of imminent submission of PhD, projected examination date and confirm award of PhD degree prior to starting the post)
• Bachelor of Medicine/ Surgery
• Experience in haematology and / or cancer research
• Experience in analysis of clinical data
• Expertise in analysis of whole exome sequencing and targeted re-sequencing variant calling, bulk RNA-seq
• Experience in analysis of sc-RNAseq and sc-ATAC-seq
• Friendly and open demeanour, evidence of being able to work effectively in a team
• Ability to work flexibly to accommodate needs of the research programme.
• Evidence of excellent organisation skills and working to deadlines
• Evidence of effective communication with academic, clinical and managerial colleagues
• Presentation skills, including evidence of presentation of research to national/ international audience
• Ability to follow the KCL safety guidelines and adhere to risk assessments and COSHH regulations

Desirable criteria

• Specialist Post-graduate Clinical Haematology qualification
• Experience in analysis of Methyl-seq e.g. WGBS or RRBS
• Experience in adapting and developing new computational approaches
• Experience in supervising junior team members
• Knowledge of cellular research techniques, including flow cytometry, cell culture, NGS library preparation and single cell techniques

Further information

Some relevant recent publications:

Quek L, David, Muriel., Kennedy, A., Metzner, M., Amatangelo, M., Macbeth, K., De Botton, S., Levine, R., Thakurta, A., Penard-Lacronique, V., Vyas, P. Clonal heterogeneity in Differentiation Response and Resistance to AG-221 in IDH2m AML. Nature Medicine 2018; 24(8):1167-77.
Amatangelo, M.A. et al., Enasidenib promotes hematopoietic differentiation to induce clinical responses in IDH2-mutant Acute Myeloid Leukemia that are modulated by co-occurring mutations. Blood. Aug 10;130(6):732-741(2017).
Goardon N et al. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011;19(1):138-52.
Quek, L. et al. Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. J Exp Med. 213(8):1513, (2016).

This advertisement does meet the requirements for a Certificate of Sponsorship under Home Office regulations and therefore the university will be able to offer sponsorship for this role.