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Postdoctoral Research Scientist in Immunology and Gene Regulation Reference number: RR-PRS-LTC Control of higher-order genome organization and enhancer function by transcription factors in CD4+ T cells. Job description We wish to recruit a highly motivated Postdoctoral Research Scientist to work in an energetic and collaborative multidisciplinary research team studying how enhancer-binding transcription factors drive sequence-dependent establishment of higher-order inter- and intra-chromosomal interactions to control CD4+ T cell differentiation and function under physiological conditions and during infections, autoimmunity and cancer. T cells coordinate immune function by differentiating into highly specialised cellular lineages that either promote or suppress immune reactions. Whereas effector T cells cause immune activation and can drive clearance of infections and cancer, regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, suppress their function, preventing excessive autoimmune and allergic reactions but promoting deleterious immunosuppression in cancer. Thus, T cells play a pervasive role in health and disease but mechanisms that control the induction and maintenance of effector and regulatory cell characteristics are incompletely elucidated. Their discovery could enable development of a powerful new class of therapies. Enhancers form higher-order looping structures with often distant genes to regulate gene transcription and programme cell-specific transcriptional outputs [1]. Genetic variations that contribute to risk of autoimmune and allergic diseases are highly enriched at enhancers, indicating their potential involvement in regulation of immune function [2]. We have recently discovered that the transcription factor, BACH2, functions as a pervasive regulator of immune activation, promoting Treg cell development while suppressing the differentiation and function of multiple effector lineages [3]. Genetic polymorphisms within the BACH2 locus are associated with susceptibility to several autoimmune and allergic diseases in humans and deletion of BACH2 in mice results in spontaneous lethal inflammation. We have found that BACH2 predominantly binds enhancers [4], but mechanisms of its action at enhancers are unclear. Based on preliminary evidence, this project will investigate how BACH2 controls inter- and intra-chromosomal interactions between enhancers and their regulatory targets in CD4+ T cells to enable appropriate control of T cell differentiation and function in response to extrinsic signals. Consequences for immune homeostasis and responses to infections and cancer will be explored. The successful applicant will join the laboratory of Dr Rahul Roychoudhuri within the Lymphocyte Signalling and Development ISP (http://www.babraham.ac.uk/our-research/lymphocyte/rahulroychoudhuri) and will work in close collaboration with the group of Dr Peter Fraser and Dr Mikhail Spivakov within the Nuclear Dynamics ISP at the Babraham Institute. The applicant will utilise cutting-edge experimental approaches in mouse immunology, molecular biology and functional genomics, including genome-wide chromosome conformation capture Hi-C, ChIP-Seq and ATAC-Seq. Highly self-motivated individuals who wish to continue their career in academic science and have the intention of eventually establishing their own independent research groups are encouraged to apply. Experience in mouse immunology, functional genomics and molecular biology, and an understanding of immunology and epigenetic regulation of gene expression and chromatin structure are advantageous as are basic skills in or an interest to learn bioinformatics. For more information on the work of the laboratory, please visit: http://www.babraham.ac.uk/ourresearch/lymphocyte/rahul-roychoudhuri Informal enquiries may be made to [email protected] Recommended reading: 1. Maurano, et al. (2012). Systematic localization of common diseaseassociated variation in regulatory DNA. Science 337:1190-5. 2. Nagano, et al. (2013). Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502:59-64. 3. Roychoudhuri, et al. (2013). BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature 498; 506-10. 4. Vahedi, et al. (2015). Super-enhancers delineate disease-associated regulatory nodes in T cells. Nature 520:558-62. 5. Schoenfelder et al. (2015). Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome. Nat Genet. Ahead of print. The position is funded by the Wellcome Trust and available for an initial period of up to 3 years. Postdoctoral Research Scientist in Immunology and Gene Regulation Reference number: RR-PRS-LTC Person Specification Education/Qualifications/Knowledge PhD in Biological Science Good knowledge of molecular biology Good knowledge of basic informatics Essential Essential Desirable Experience Experience in protein biochemistry Experience in mouse immunology Experience in functional genomics, including promoter-capture Hi-C An understanding of immunology and epigenetic regulation of gene expression and chromatin structure Desirable Desirable Desirable Desirable Skills/Abilities Excellent comprehension and communicate in the English language Ability to work independently and as part of a team Ability to communicate effectively with staff at all levels, both orally and in writing Good scientific writing skills Good presentation skills Essential Essential Essential Essential Desirable Personal Characteristics Passionate for science, in particular life sciences Curious and always try to understand before seeking help Enthusiastic and highly motivated Ability to work independently while considering the needs of others Essential Essential Essential Essential Special Requirements Ability to work in a non-smoking environment Essential The Babraham Institute Postdoctoral Research Scientist in Immunology and Gene Regulation Reference number: RR-PRS-LTC INFORMATION ON TERMS & BENEFITS The following is for information only and is not contractual statement of terms and conditions. Pay Grade BI 6 Salary £29,557 per annum to £32,840 per annum Working Hours 37 hours per week Holiday Entitlement 25 days per annum Public Holidays & Privilege Days 10½ days Length of Contract Funding available for three years Pension Scheme Babraham Institute is able to offer membership of a Group Personal Pension Scheme. We will provide you with details of this scheme once you commence work. Membership of the scheme is not compulsory but it is designated as Babraham Institute’s Stakeholder exempt plan. The Institute does not make contributions to other personal pension schemes. Restaurant Facilities The Refectory serves hot meals and snacks and the Forum provides a selection of snacks and hot and cold beverages for coffee and tea breaks. Onsite Accommodation The Institute has a number of hostels, flats and houses which can be rented. (There is currently a waiting list for all types of accommodation.) Social Sports & Social Club Nursery Nursery and Holidays Playscheme on site. (Availability of places is dependent on demand.) Car Parking There is free car parking in the Institute Car Park. The Institute is committed to the implementation of a commuting strategy to try and reduce the growth in numbers of cars used to travel to work Any offer of employment will be subject to security screening and may be subject to health screening. Any offer may also be subject to a general medical.