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Transcript
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.