Research Assistant in Epigenetic Regulation of Differentiation of IDH-mutant AML Progenitors
- Full Time
The postholder will be a key researcher in a new project funded by a research grant from Bristol Myers Squibb 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, who leads the Myeloid Leukaemia Genetics and Biology Group 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 Enasidenib have recently been developed and FDA-approved to treat IDH-mutant AML. We have shown that Enasidenib restores 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 Enasidenib 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 a early career researcher who takes pride in performing scientific work to high technical standards, has excellent organisation skills, is ready to take on new challenges. This postholder will be a key member of a team to study the genetic and epigenetic events which underlie cell fate decisions in human patient IDH-mutant AML cells treated with IDH inhibitors.
The ideal candidate will have knowledge or experience in flow cytometry, tissue culture, gene-editing techniques, in vitro functional assays, and genomics (including DNAseq, RNAseq, MethylSeq and ATACseq). Training in more advanced techniques (e.g. flow-sorting, single cell genomics) will be offered, and the postholder will be expected to be self-driven in developing new skills. The postholder will have the opportunity to acquire basic computational skills.
We are looking for a candidate who is enthusiastic about translational research and who is able to demonstrate self-motivation, flexibility and good teamwork. This post will be ideal for a recent graduate, looking for their first or second research position. S/he will gain most from this post by having a high level of commitment to this project and a true passion for furthering clinical scientific research. The successful candidate will also benefit from being able to work with a post-doctoral scientist in this project.
Dr Quek is especially interested in helping promising researchers develop their career. This project will provide excellent scientific and technical training, working in an area that has direct relevance to patient care. Although this post has a fixed term of 12 months, there is the possibility of extension for a further 12-24 months through other funding streams.
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 post will be offered on a fixed-term contract for 12 months
This is a full-time post - 100% full time equivalent
• Motivation to perform research to the highest standards
• Management of own research and administrative duties, planning, developing and executing experiments in discussion with senior team members
• Be highly organised and be able to work effectively to deadlines
• Contribute directly to scientific discussions with Dr Quek and other members of the group
• Work as part of a team to prepare data reports and documentation
• 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.
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
• Bachelor degree in relevant area of Genetics, Cellular/ Molecular Biology or Biochemistry
• Knowledge of genetics and basic concepts in blood cancers, generation sequencing technologies cell culture, basic molecular biology (PCR, qPCR) and cell separation techniques
• Evidence of good numerical and reasoning skills
• Expertise in basic IT (Word/ Excel/ Powerpoint) and data analysis tools
• 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 accurate and timely documentation and record-keeping
• Evidence of effective communication with team members/ colleagues
• Experience in working in a lab, tissue culture or handling of primary patient samples, basic molecular biology techniques, preparation of NGS libraries
• Experience in Illumina NGS platforms
• Evidence of self-motivated learning
Dr Quek’s group is part of a research programme at the Comprehensive Cancer Centre dedicated to translating research into better treatments for patients.
The other groups focused on blood cancers include: Leukaemia Stem Cell Biology (Professor Eric So), Gene & Cell based therapies (Professor Farzin Farzaneh), CAR-T Cell Programmes (Professor Ghulam Mufti), bone marrow failure syndromes (Professor Judith Marsh), post-transplant immunotherapies (Professors Francesco Dazzi and A. Pagliuca and Dr. Victoria Potter) and King’s College Hospital Heamato-oncology Molecular Diagnostics Centre (Robin Ireland).
These research programmes benefit from an extensive Biobank of blood cancers, and a recent investment in infrastructure and new equipment. Research groups at Denmark Hill will have on-site access to a BD Aria Fusion Flow Sorter, BD Lyric Flow Analyzers, a Helios CyTOF, an Illumina NextSeq Sequencing System, 10x Genomics Chromium platform and automated sample and nucleic acid handling systems.
These research programmes are closely linked to clinical services, where research activities are translated into novel therapies including CAR-T cells/immunotherapies (with specific emphasis on allogenic CART-T clinical trials in Lymphomas/ALL & AML).