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Multiple sclerosis: understanding genetic and environmental susceptibility

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About the Research

Professor Lars Fugger leads a neuroinflammatory research group (www.ocni.co.uk), with the primary research focus being to understand the genetic and environmental risk factors that cause multiple sclerosis. Multiple sclerosis (MS) is a common neuroinflammatory autoimmune disease that effects the brain and spinal cord, leading to reduced coordination, visual impairment and eventual permanent paralysis. The disease typically occurs in young adults and has no known cure.

Genetic analysis of patients with MS has revealed over 100 genetic risk loci attributed to increasing risk to developing the disease, in addition to a number of environmental stimuli, including infections, vitamin D levels and smoking. Despite all of this knowledge, the mechanisms and pathways that cause the disease are still unclear and we are unable to predict who will or will not develop the disease or how best to treat patients once diagnosed. The aim of our lab is to interrogate genetic risk for MS using a platform of new technologies that enable a power of resolution within these genomic risk regions at a level that has not been possible previously.

As part of a DPhil studentship, you will gain extensive experience working with human samples, including blood samples from healthy control and MS patients as well as post mortem tissue. Processing of samples will require the use of several cutting-edge techniques, such as ATAC-sequencing, chromatin conformation capture, and single cell RNA sequencing, in addition to the use of standard laboratory techniques such as cell culture, molecular biology and flow cytometry.

Our research group has a strong local, national and international collaborative network of biologists, clinicians and statisticians, where novel and emerging techniques are continually introduced into our experimental and analytical platforms. A DPhil project will therefore encompass the use of both current and newly developing technologies in which to conduct a research project, which aims to take us a step further towards understanding the complexity of why people develop MS and to identify novel disease pathways that can be targeted for new treatments.

 

Training Opportunities

Our lab consists of highly experienced scientists, including 3 senior-postdoctoral and 3 postdoctoral researchers, 2 senior postdoctoral statisticians and a research assistant. Research projects in the group involve multidisciplinary skills and therefore our projects require continuous team involvement within the lab. You will receive training for the techniques required for your research project within the group and any further skills required will be achieved on a collaborative basis with other labs, if needed. 

 

Students will be enrolled on the MRC WIMM DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

 

Publications

Cortes A, Dendrou CA, Fugger L, McVean G. Systematic classification of shared components of genetic risk for common human diseases. 2018. Science: under review

Cortes A, Dendrou CA, Motyer A, Jostins L, Vukcevic D, Dilthey A, Donnelly P, Leslie S, Fugger L, McVean G. Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank. Nat Genet. 2017 Sep;49(9):1311-1318

Kaur G, Gras S, Mobbs JI, Vivian JP, Cortes A, Barber T, Kuttikkatte SB, Jensen LT, Attfield KE, Dendrou CA, Carrington M, McVean G, Purcell AW, Rossjohn J, Fugger L. Structural and regulatory diversity shape HLA-C protein expression levels. Nat Commun. 2017 Jun 26;8:15924

Dendrou CA, Cortes A, Shipman L, Evans HG, Attfield KE, Jostins L, Barber T, Kaur G, Kuttikkatte SB, Leach OA, Desel C, Faergeman SL, Cheeseman J, Neville MJ, Sawcer S, Compston A, Johnson AR, Everett C, Bell JI, Karpe F, Ultsch M, Eigenbrot C, McVean G, Fugger L. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med. 2016 Nov 2;8(363):363ra149

Fugger L, McVean G, Bell JI. Genomewide association studies and common disease--realizing clinical utility. N Engl J Med. 2012 Dec 20;367(25):2370-1

Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, Poschmann G, Kaur G, Lambert L, Leach OA, Prömel S, Punwani D, Felce JH, Davis SJ, Gold R, Nielsen FC, Siegel RM, Mann M, Bell JI, McVean G, Fugger L. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012 Aug 23;488(7412):508-511


Supervisors