Genetics & Molecular Medicine (Research Division)

The Division consists of four Departments, all of which focus on investigation of the molecular basis of human disease, and how such knowledge can be applied to improved diagnosis and therapy.As an indication of the quality of our research programme, of the four KCL researchers named in the 2014 global list of the most highly cited researchers, 3 are members of the Division. This prestigious list, published by Thompson Reuters, recognises ‘the best and brightest scientific minds of our time’, by determining which researchers have produced work that is most frequently acknowledged by their peers. Tim Spector, Professor of Genetic Epidemiology, Christopher Mathew, Professor of Molecular Genetics, and Tim Hubbard, Professor of Bioinformatics, are included in the list which identifies them as being among the world’s leading and most influential experts in their respective fields.

The Department of Medical & Molecular Genetics aims to identify genes, their functions, and variants, implicated in both Mendelian and complex common disorders, with a strong emphasis on translational medicine. Current studies use new-generation high-throughput DNA sequencing and genotyping technology to identify genetic variants associated with common inflammatory disorders such as inflammatory bowel disease, psoriasis and systemic lupus erythematosus, and to find causal mutations in a range of rare and severe genetic syndromes.

There is also a strong cancer genetics group studying the molecular origins of breast cancer, leukaemia and oesophageal cancer. Further substantial research programmes exist in neurogenetics, including basic and translational aspects of Huntington's disease, while other work explores epigenetic effects such as imprinting, the control of gene expression, and epistatic interactions between genes. Several research groups are involved in development of statistical approaches to whole genome association studies and the integration of emerging biological databases with genomic studies. The Department has close links with our NHS Department of Clinical Genetics and its associated diagnostic laboratories, which provide genetic services to a large patient base in the south-east of England.

The Department has state-of-the-art laboratories and equipment, including a core Genomics facility, which, in partnership with our Biomedical Research Centre, houses next-generation DNA sequencers and microarray facilities for high-throughput DNA sequencing, genotyping and analysis of gene expression. There is also a substantial computing infrastructure for bioinformatics, and an imaging laboratory for confocal and laser dissection microscopy.

The research strategy of St John's Institute of Dermatology seeks to improve the diagnosis and management of severe skin diseases through a better understanding of the basic pathogenetic mechanisms that cause and sustain these conditions. It targets four key areas: cutaneous oncology, genetic skin disorders, inflammatory and autoimmune skin disorders, and photomedicine. Research methods extend from molecular genetic analysis to therapeutic intervention studies. Work in progress embraces both collaborations within King's College London and external collaborations world-wide.

The close relationship between scientists, clinicians and clinical resources allows for shared knowledge, flow of patient material (eg skin biopsies, blood samples) to the laboratories and dissemination of scientific knowledge to clinicians, fostering an atmosphere of science-based clinical practice and translational research. Members of the department belong to an MRC cooperative group (FRET/FLIM microscopy in cell migration). Research facilities within the Institute are designed to enable translational human skin biological research and include cell biology (including cell transfection), immuno-labelling and photomicroscopic facilities, molecular genetic facilities and in vivo sampling techniques (phototesting, skin biopsy, DNA sampling), with appropriate storage techniques. The department is situated in 850m2 of new laboratories, together with appropriate facilities, on the Guy's Campus, adjoining the Department of Medical & Molecular Genetics.

The Department of Twin Research and Genetic Epidemiology (DTR), headed by Professor Tim Spector, hosts one of the largest twin databases in the world (TwinsUK), with a total of 13,000 twins, with the most detailed phenotype and 'omic information on twins available worldwide, allowing collaborative work with a range of scientists from different specialities and disease areas. The TwinsUK Registry, funded by the Wellcome Trust, has been responsible for demonstrating the genetic heritability of a number of diseases that were believed to be caused by age and environment alone. The DTR has also set up a unique cohort of 1003 aging women followed for 18 years (the Chingford study), which produced valuable data on the natural history and progression of age-related and musculoskeletal diseases. The DTR has participated in a number of FP6 and FP7 EU projects and was the coordinator of a number of EU projects involving seven other institutions looking at the genetics of clotting and strokes; it has also coordinated an FP7 project which included nine other partners and looking at Translational Research in Europe Applied Technologies for Osteoarthritis (TreatOA). Current projects co-ordinated by the DTR, funded by the EU, include the “EpiTwin” project which is looking at the epigenetic markers within 5,000 twins, “EuroBATS” which is looking at a number of ‘omics’ techniques including transcriptomics, “EurHEALTH” which is looking at many aspects of ageing, and the Marie Curie ITN project, EpiTrain, which is a Europe-wide network set up to provide training to young researchers in epigenetics. In addition the DTR is a partner on PainOMICS, looking at biomarkers for pain. The principal focus of research uses an ‘omics’ approach to study common complex diseases of aging (including cardiovascular disease, metabolic syndrome and type 2 diabetes), healthy ageing and eyes. This ‘omics’ approach incorporates the use of genomic, epigenomic, transcriptomic, metabolomic, glycomic, proteomic and gut microbiome data.

The Centre for Stem Cells and Regenerative Medicine is led by Prof Fiona Watt FRS. She is particularly interested in how stem cells interact with their local environment, or niche, and believes that an understanding of these interactions is important for developing effective cell therapies in the clinic. Located on the Guy’s Hospital campus, the Centre acts as a focus for cutting-edge stem cell research taking place across the College and its partner NHS Trusts, as part of King’s Health Partners. There are currently four groups in the Centre, with expertise encompassing stem cells in adult epidermis, human induced pluripotent stem cells, hepatocytes for liver repair and analysis of Wnt signalling at single cell resolution.

Graduates work with a particular research group, under the guidance of a primary supervisor. They also have a second supervisor, who follows the work closely and is involved in upgrades, thesis writing, and scientific mentoring. They meet regularly with their supervisor(s), usually on a weekly basis, and his/her group, and will attend weekly laboratory meetings, where they will be expected to participate and present their work.

All students are required to produce six-monthly progress reports, which are submitted to the School's Postgraduate Research Committee. All graduate students are expected to attend the regular laboratory and Divisional meetings and the annual Graduate Research Showcase Event held by the School. The Division holds monthly Polani Seminars with prestigious speakers, and has a weekly seminar programme which alternates between GMM seminars designed to showcase the work of specific research groups, and a Student Seminar programme at which postgraduate students make short presentations on their work. These are intended to develop new collaborations, strengthen selected areas of research (particularly in areas given high priority by the government, research councils, the Wellcome Trust and NHS), implement further translational research between academic and clinical colleagues, and develop facilities for new technologies.

In 2015/2016, subject to approval, the Department of Medical and Molecular Genetics will be introducing a one-year taught MSc in Genomic Data Analysis, which is intended to provide biomedical graduate students with the knowledge and skills needed to engage and analyse large 'omic' datasets - in particular those arising from next-generation sequencing. This is a practical, hands-on data analysis course. The emphasis throughout will be on the analysis of real, large-scale genomic data, to answer questions of translational value in medical research.