THE WELLCOME TRUST CENTRE FOR HUMAN GENETICS Job Description Job Title: Post Doctoral Research Scientist in Statistical Genetics Tenure: 24 months in the first instance. Grade: Grade 7, £28,983 to £35,646 with a discretionary range to £38,951 Funded By: The Wellcome Trust SUMMARY The groups led by Dr Andrew Morris, Dr Cecilia Lindgren and Prof Mark McCarthy at the Wellcome Trust Centre for Human Genetics, and by Dr Eleftheria Zeggini at the Wellcome Trust Sanger Institute plan to make a joint appointment for an experienced statistical geneticist. The main focus of the work will relate to transethnic fine-mapping efforts in type 2 diabetes, making use of data and resources arising from the NIH-funded T2D-GENES study. This international collaborative effort has access to extensive genome- wide association data from multiple ethnic groups, and is generating substantial genome-scale next- generation sequence data. The person appointed will take a leading role in the analysis of these data. The successful candidate will have a PhD in a relevant subject, experience of analysing genome-scale association data from diverse ethnic groups, a thorough understanding of imputation procedures, familiarity with diabetes genetics, and previous involvement in international research efforts. The post will be based at the Wellcome Trust Centre for Human Genetics, but the candidate will be expected to spend part of the project at the Wellcome Trust Sanger Institute. We anticipate substantial interactions with colleagues in the US and elsewhere. BACKGROUND The environment: The Wellcome Trust Centre for Human Genetics The WTCHG (Director: Professor Peter Donnelly, FRS) is one of the leading international centres for the study of the genetic basis of common human diseases. As well as hosting a number of high-profile groups pursuing the genetic basis of diabetes, cardiovascular disease and neuropsychiatric phenotypes (amongst others), the WTCHG has led the efforts of the Wellcome Trust Case Control Consortium and been responsible for advancing the application of large-scale genetic analysis to the dissection of common human phenotypes. The centre provides a unique integrated environment – including core genomics facilities, bioinformatics and statistical genetics. Since 2005, there have been 40 publications in Nature, Science, Nature Genetics, Nature Medicine, Nature Immunology, Nature Structural and Molecular Biology, Cell, or Molecular Cell on which Centre scientists have earned either first or last author positions, and a further 34 papers in these journals on which Centre scientists have collaborated. The WTCHG provides an extremely strong computing infrastructure for genetic analysis and has recently invested heavily in high-throughput next-generation resequencing. The WTCHG currently has installed 7 Illumina and 2 Roche/454 high-throughput (HT) sequencers. The WTCHG forms part of the Nuffield Department of Medicine at the University of Oxford, one of the strongest departments of clinical academic medicine in the country (see www.ndm.ox.ac.uk for further details). The project: Trans-ethnic fine mapping in type 2 diabetes This post is funded through grants from the US National Institutes of Health and the Wellcome Trust, and will be focused around the trans-ethnic fine mapping of type 2 diabetes loci. Though genome wide association scans have identified ~40 loci influencing T2D-risk, in very few cases have the variants causal for the association been characterised. Extensive linkage disequilibrium typically means that, even after exhaustive sequencing has been performed, within any given population, a number of highly-correlated SNPs show indistinguishable evidence for association. It has long been suspected that one might be able to refine the associations further if one had access to data from diverse ethnic groups (particularly, but not exclusively, those of African origin) since differences in the patterns of LD and haplotypes might allow the effects of variants that are closely-correlated in one population to be distinguished. The availability of large-scale GWAs data for many different major ethnic groups, together with increasingly comprehensive surveys of common and low frequency variation (arising from the 1000 Genomes Project for example) means that it is now possible to conduct transethnic fine mapping studies of this kind, and the position being advertised will be involved in efforts to do precisely this for T2D. The work will take place in the context of the T2D-GENES consortium, funded by NIDDK to a total of $25M through the U01 mechanism in 2009. The consortium includes many of the major groups worldwide working on T2D genetics, and provides access to many T2D case-control samples of diverse ethnic origin (many of which have already been GWAS’d). The consortium is using its funding to undertake a number of targeted and exome-sequencing projects designed to identify low frequency and rare variants influencing T2D risk, but it is also devoting efforts to perform fine-mapping of the original common variant signals using a range of in silico approaches. These efforts are broadly based around taking existing GWAs data, performing imputation from 1000 Genomes, and then using a range of different analytical approaches to identify putatively causal variants (under a range of different possible models). Whilst the person in post will likely be involved in several different aspects of the evolving T2D-GENES consortium effort, the primary responsibility in the first year at least will be to support the common- variant fine-mapping analyses described above. This particular subproject is currently being run by a group of investigators based in Oxford, Sanger and Singapore, each of which has developed or is championing an alternative analytical approach. As well as comparing these different approaches through simulations, we are also gathering data from GWAS’d cohorts of diverse transethnic backgrounds so we pipe these through the various analytical approaches and determine how well they correspond in terms of their findings. WE are initiating this project through analysis of five T2D- susceptibility loci of particular interest, but expect to expand the project more widely over the course of the next year (ultimately to genome-wide analyses). The group leaders Mark McCarthy is Robert Turner Professor of Diabetes at the Oxford Centre for Diabetes, Endocrinology and Metabolism and Group Head at the Wellcome Trust Centre for Human Genetics. He heads one of the leading international groups working on the genetics of type 2 diabetes and related conditions. Andrew Morris is a Wellcome Trust Senior Fellow at the Wellcome Trust Centre for Human Genetics. He has interests in the development of novel statistical approaches to genetic analysis, and in their application to genome-scale data. Cecilia Lindgren is a Wellcome Trust Career Development Fellow at the Wellcome Trust Centre for Human Genetics. She is vastly experienced in the analysis of genetic and genomic data, and has a particular interest in the genetics of obesity and fat distribution. Eleftheria Zeggini is an Investigator at the Wellcome Trust Sanger Institute, with extensive experience in the development and application of novel statistical methods for the analysis of genome-scale data. She has particular interest in the evaluation of the contribution of low frequency variants to common disease etiology. All four groups work extremely closely on a variety of common projects including the T2D-GENES consortium projects on T2D fine-mapping. The Post We are looking to appoint a postdoctoral scientist with the skills already in place that will allow them to contribute substantively to the work outlined above. The research will involve the manipulation and analysis of very large (genome-scale) data sets (eg GWA data sets, 1000Genomes imputation), so existing experience in this area will be absolutely essential. As well as generating data from existing T2D case-control GWA analyses, the person in post will be involved in the collation of such data from multiple ethnic groups, and then for the analysis of those data using some of the analytical approaches that the group collectively plans to apply (these include TRANSMAP, AMELIA and CAUSAL-SEEK). As results emerge, the person in post will have responsibility for comparing the outputs of the different programs, to identify putatively causal alleles that can be put forward for further validation and/or functional evaluation. In addition to this work on the common variant transethnic mapping project, we expect the person in post to become involved with other efforts of the T2D-GENES consortium, as well as other major projects underway in the Oxford and Sanger groups. These include the GOT2D project which is currently obtaining genome-wide sequence data on ~1500 t2D cases and 1500 controls as a means to evaluate the role of low frequency variants on T2D risk. Given the nature of the project (and the short time-lines for implementation), we will be looking to appoint only those individuals who can demonstrate considerable relevant experience. We expect this to include a PhD or equivalent in a relevant subject (natural sciences, mathematics, statistics, computer science, genetics, biology), though, exceptionally, we would consider applications from those without a PhD if they can demonstrate a significant body of work of post-doctoral quality, or extensive industrial experience in the management of large, complex data sets. The post will be based at the Wellcome Trust Centre for Human Genetics in Oxford, though we anticipate that at least part of the project will be undertaken at the Wellcome Trust Sanger Institute (where the person in post would be granted a Visiting Fellowship). There will also be extensive interactions with other groups in the T2D-GENES consortium and other major projects ongoing in the department. Responsibilities Main responsibilities To report to Prof McCarthy and Drs Morris, Zeggini, Lindgren, meeting regularly to ensure that appropriate work is performed; To develop, implement and maintain software pipelines required to pursue the objectives of the project; To manage data generated by the project; To participate in group meetings, generate high-quality manuscript, and contribute to discussions of the aims and objectives of the group; To contribute ideas and communicate effectively with all project participants including international travel where required; To keep abreast of the relevant literature and methodology developments as they pertain to the work; To hold frequent discussions with other members of the T2D-GENES consortium and other groups that may be relevant to pursuit of the objectives of the research; To perform any other comparable duties as may reasonably be required to ensure the efficient running of the project. General responsibilities To be accountable for your professional conduct within the Group and the Centre To undertake such other duties as may be required from time to time that are commensurate with the grade and responsibilities of this post. To ensure such that all conduct is with due regard to the University Equal Opportunities and Data Protection policies Relationships The primary responsibilities for line management will rest with Prof McCarthy and Dr Morris, though the person in post will also interact closely with Dr Lindgren and Dr Zeggini and other members of their teams. Other relationships will include: Prof Peter Donnelly (as Director of the WTCHG) Dr Mike Boehnke (as leader of the T2D-GENES consortium) Selection criteria Essential PhD in a relevant subject Proven experience in the genetic analysis of multifactorial traits Experience in analysing genome-scale association data Practical understanding of imputation procedures Desirable Experience in analysing genome-scale association data from diverse ethnic groups Experience of working on the genetics of type 2 diabetes Practical experience of working as part of an international collaborative team A good understanding of other aspects of the project including epidemiology, genomics and/or molecular biology, and project management Working for the University of Oxford At the University of Oxford, we’re naturally very proud of our outstanding reputation for scholarship and research. But we’re also proud to say that we’re one of the region’s biggest and best-established employers, with a diversity of staff helping to sustain our success – from laboratory assistants, cleaners, technicians and secretaries, to IT, finance and administrative professionals. Join us, and you can expect to find yourself working in a friendly, open-minded atmosphere where your ideas will be welcomed, with an interesting and satisfying job to do, and with plenty of opportunities to learn new skills, or maybe even get some extra qualifications. As well as pay and other benefits such as generous holidays and excellent pension scheme, we may be able to help you with: Training – We train our staff, both in the skills needed for starting the job, and to help them develop afterwards. If you don’t have all the skills we are looking for (e.g. computer packages), but you know you are a quick learner, its worth asking if training might be available. Working Hours – We may be able to be flexible about working patterns to help you combine work with responsibilities at home. Even for full-time jobs, we can often adjust starting and finishing times, or even sometimes consider term-time-only working: if this is important to you, let us know. Disability – If you have a disability, we have specialist staff who can help you to start and stay in work. Childcare – We have several subsidised nurseries for under-fives, a holiday play scheme, tax and national insurance savings schemes, and are looking to expand our facilities. For further information see www.admin.ox.ac.uk/eop/child. Parenting – As well as providing childcare facilities, we have generous maternity; paternity and adoption leave schemes to help new parents on our staff. Cultural and Religious needs – We respect the cultural and religious lives of our staff. If you need time away from work, or special facilities, and can give plenty of notice for arrangements to be made, this will always be considered. Travel Arrangements – We offer an interest free-season ticket loan scheme for bus or train season tickets. Annual passes for Oxford Bus Company routes are available at discounted rates. Use of University Facilities – All University staff can use the study facilities provided by the University libraries and museums; join the University Club, a sports and social club which has its own bar, café, and reading room; and make use of the University Sports Complex and the Pulse fitness centre. Discounts – A number of discounts are available to University staff e.g. for insurance, holiday travel, and computer equipment. The range of benefits is continuously reviewed and extended. For further information see www.admin.ox.ac.uk/ps/staff/benefits/ If you come from outside the area, you may be interested to know that as well as the famous tourist attractions such as the ‘dreaming spires’ of all the lovely old buildings, the river and a number of attractive parks and gardens, Oxford also has a busy shopping centre and a lively nightlife, particularly during term time. Housing is relatively expensive within the city, but nearby areas are more reasonable priced. Although car parking is difficult during the day, there are good train and bus services, including several ‘Park and Ride’ routes; and of course, lots of cycle paths. The University has a generous maternity leave scheme and also offers paternity leave to expectant fathers and partners, and adoption leave. It offers subsided nursery places, a holiday playscheme, and tax and National Insurance savings schemes. For further information see www.admin.ox.ac.uk/eop/child Pay and Benefits The salary offered for full-time appointment to this job will be grade 7 (£28,983 to £35,646, with a discretionary range to £38,951). There is an annual ‘cost of living’ salary review, which normally takes place in summer each year. Pay and benefits for part-time appointments are worked out on a ‘pro rata’ basis. For a full-time appointment, the annual holiday entitlement will be 38 days (including 8 public holidays). Your hours of work are such as are reasonably required to carry out your duties to the satisfaction of your head of department. The appointment is subject to satisfactory completion of a 6 month probationary period, during which the notice period will be one month on either side. Once the appointment has been confirmed, the notice period will be three months either side. The position is available for 24 months in the first instance and will be funded by the Wellcome Trust. Staff The age of retirement for university appointments is 65. Staff are eligible to join the Universities Superannuation Scheme (USS) which is a contributory scheme. Subject to the Statement of Pensions Policy, which will be issued to the successful candidate, the appointee will be deemed to be in membership of the USS until such time as he or she gives notice in writing to exercise the right not to be a member of the scheme. The Wellcome Trust Centre for Human Genetics has a NO SMOKING policy. How to apply To apply, please write a letter of application and send a detailed CV and return it to: Personnel Administrator Wellcome Trust Centre for Human Genetics Roosevelt Drive Oxford OX3 7BN or by fax to 01865 287516 or email to firstname.lastname@example.org by no later than Friday 30th July 2010. Applicants received after this date will not be considered. Please make sure you quote reference number H5-10-042-CL at the beginning of your application. The list of duties and the ‘selection criteria’ for this job describe the sort of skills, experience, knowledge or abilities which we are looking for. We will interview those whose applications best meet these criteria, so it is very important that you should use your application to explain how you can match them. Remember that you will have gained abilities, experience and skills from many aspects of your life; some may come from education or work, and others from home or community life. Tell us about which schools or colleges you went to and any qualifications you have. List employment, voluntary work, hobbies, or family responsibilities which help to show you meet the selection criteria. Please give the names, addresses and telephone numbers of two people you are prepared to give you a reference for this job. If you have previously been employed, your referees should be people who have direct experience of your work through closely working with you for a considerable period, and at least one of them should be your formal line manager in your most recent job. Otherwise they can be people who know you from recent college, school, or voluntary experience. It is helpful if you can tell us briefly how each referee knows you (e.g. ‘line manager’. ‘Work colleague’, ‘college tutor’). Your referees will be asked to look at the job details and tell us if, in their opinion, you could do the job. We will assume that we can approach them at any stage unless you tell us otherwise when you apply. So, if you wish us to ask for your permission before approaching a particular referee, or to contact them only under your circumstances (for example if we are calling you for a interview, or if we have made you a conditional offer), you must state this explicitly alongside the details of the relevant referee(s). Your appointment will be subject to (i) the return of a completed medical questionnaire which is acceptable to the University, (ii) the provision of original documentation which indicates your right to work in the UK, and (iii) the completion of an initial probationary period of 6 months. Please note that due to the volume of applications we receive it will only be possible for us to contact those who have successfully been shortlisted to attend interview. Equal opportunities at the University of Oxford As an Equal Opportunity employer, we positively encourage applications from people of different backgrounds. All our jobs are filled in line with our equal opportunities code of practice, which helps us make sure that men and women, people of different races, and those with disabilities are all treated fairly. If you have any questions about equal opportunities at the University of Oxford, please visit our website at www.admin.ox.ac.uk/eop General Responsibilities To participate and support public engagement activities on behalf of the Centre, working with the Centre’s Public Engagement and Communications Officer. This is anticipated to be around 2 days per year. Data Protection All data supplied by applicants will be used only for the purpose of determining their suitability for the post, and will be held in accordance with the principles of the Data Protection Act 1998 and the University’s Data Protection Policy. POLICY STATEMENT The policy and practice of the University of Oxford require that all staff are afforded equal opportunities within the employment and that entry into employment with the University and progression within employment will be determined only by personal merit and the application of criteria which are related to the duties of each particular post and the relevant salary structure. In all cases, ability to perform the job will be the primary consideration. Subject to statutory provisions, no applicant or member of staff will be treated less favourably than another because of his or her sex, martial status, sexual orientation, racial group, or disability.
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