Imperial College London
Job Description
Job Title:
Research Assistant
Centre:
Pathology
Division:
Experimental Medicine
Department:
Medicine
Job Family and Level:
Academic and Research, Level A
Salary Range:
£28,200 - £32,150 per annum
Responsible To:
Professor Richard Festenstein
Working Relationships:
Colleagues in the Gene Control and Mechanisms and
Disease Group (CSC)
Location:
Hammersmith Campus
Duration:
Full-time, fixed-term for 36 months
Project Title:
Bioinformatic analysis of epigenetic effects and sexual
dimorphisms in autosomal gene expression due to sex
chromosome complement effects rather than
phenotypic sex
Job Summary
Differences between males and females are normally attributed to developmental
and hormonal differences between the sexes. We have recently demonstrated
differences between males and females in gene silencing using a heterochromatinsensitive reporter gene in vivo (Wijchers and Festenstein, 2011; Wijchers et al.,
2010). Using ‘sex-reversal’ experimental models with varying sex chromosome
complements, we found that this differential gene silencing was determined by X
chromosome dosage, rather than sex. Genome-wide transcription profiling showed
that the expression of hundreds of autosomal genes was also sensitive to sex
chromosome complement. These genome-wide analyses also uncovered a novel
role for Sry in modulating autosomal gene expression in a sex chromosome
complement-specific manner. The identification of this additional layer in the
establishment of sexual differences has important implications for understanding
sexual dimorphisms in physiology and disease and has attracted considerable
interest (Maatouk and Capel, 2010; Pirrotta, 2010). The candidate will participate in a
project which employs transgenic tools combined with high-throughput sequencing
and bioinformatic analyses to unravel the molecular basis for this novel system. We
will investigate the hypotheses that the sex chromosome effect on heterochromatin
silencing and autosomal gene expression is due to: 1) the inactive X chromosome
acting as a sink for heterochromatin factors and 2) overexpression of genes that
escape X chromosome inactivation. Moreover, we have found significant enrichment
within the subset of sex chromosome sensitive genes for genes that are also
sensitive to the dosage of a key component of heterochromatin, HP1. These genes
cluster in regions along the chromosome and bioinformatic analysis indicates that
particular repetitive sequence motifs are enriched in their vicinity. We will investigate
whether these genes are ‘responders’ to the sex-chromosome complement effect
and whether the mechanism of response involves classical features of
heterochromatin nucleated by repetitive sequences. In addition, we will investigate
whether the Sry modulatory effect is mediated directly or indirectly. These studies are
now a crucial step in unraveling the molecular mechanism that underpins sexual
dimorphisms due to sex chromosome complement effects rather than phenotypic sex
and are therefore likely to have important implications for several diseases that are
strongly sexually dimorphic particularly those with an autoimmune basis.
Interestingly, our gene ontology analysis (Wijchers et al., 2010) indicates that
metabolic genes are over-represented in the sexually dimorphic autosomal genes
compared with the transcriptome. This is particularly interesting in the light of a
number of recent studies linking epigenetics with metabolism.
Wijchers, P. J., and Festenstein, R. J. (2011). Epigenetic regulation of autosomal
gene expression by sex chromosomes. Trends Genet 27, 132-140.
Wijchers, P. J., Yandim, C., Panousopoulou, E., Ahmad, M., Harker, N., Saveliev, A.,
Burgoyne, P. S., and Festenstein, R. (2010). Sexual dimorphism in mammalian
autosomal gene regulation is determined not only by Sry but by sex chromosome
complement as well. Dev Cell 19, 477-484
Main Duties
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analysis of gene expression using RNA-seq and ChIP-seq data and
development of appropriate bioinformatic tools to analyse the data in
conjunction with Dr Boris Lenhard (MRC CSC).
to ensure the validity and reliability of data at all times
to maintain accurate and complete records of all findings
to assist with the writing of reports to research sponsors
to present findings to colleagues
to provide advice to other staff and students
to assist with the publication of findings
to attend relevant workshops and conferences as necessary
to develop contacts within the College and the wider community
to promote the reputation of the Group, the Department and the College
Other Duties
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to undertake any necessary training and/or development
to undertake appropriate administration tasks
to attend relevant meetings
any other duties commensurate with the grade of the post as directed by line
manager/supervisor
To observe and comply with all College policies and regulations, including the
key policies and procedures on Confidentiality, Conflict of Interest, Data
Protection, Equal Opportunities, Financial Regulations, Health and Safety,
Imperial Expectations (for new leaders, managers and supervisors),
Information Technology, Private Engagements and Register of Interests, and
Smoking.
To undertake specific safety responsibilities relevant to individual roles, as set
out on the College Website Health and Safety Structure and Responsibilities
page
(http://www3.imperial.ac.uk/safety/policies/organisationandarrangements).
Job descriptions cannot be exhaustive and the post-holder may be required to
undertake other duties, which are broadly in line with the above key
responsibilities.
Imperial College is committed to equality of opportunity and to eliminating
discrimination. All employees are expected to adhere to the principles set out
in its Equal Opportunities in Employment Policy, Promoting Race Equality
Policy and all other relevant guidance/practice frameworks.
Person Specification
Imperial Expectations
These are the 7 principles that Imperial leaders, managers and supervisors are
expected to follow:
1) Champion a positive approach to change and opportunity
2) Communicate regularly and effectively within, and across, teams
3) Consider the thoughts and expectations of others
4) Deliver positive outcomes
5) Encourage inclusive participation and eliminate discrimination
6) Support and develop staff to optimise talent
7) Work in a planned and managed way
Qualifications
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Degree or equivalent in a biological sciences subject or a similar field and/or
relevant experience in bioinformatics or epigenetics.
Knowledge/Experience
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knowledge of basic laboratory techniques
knowledge of basic research methods and statistical procedures including
experience in the analysis of epigenetic data using advanced bioinformatic
techniques
previous experience in a research environment
Skills and Abilities
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ability to conduct a detailed review of recent literature
ability to develop and apply new concepts
creative approach to problem-solving
excellent verbal communication skills and the ability to deal with a wide range
of people
excellent written communication skills and the ability to write clearly and
succinctly for publication
ability to organise own work with minimal supervision
ability to prioritise own work in response to deadlines
advanced computer skills as applied to Bioinformatics
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Personal Attributes
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Other
willingness to undertake any necessary training for the role
willingness to work as part of a team and to be open-minded and co-operative
excellent organisational skills
a meticulous approach and attention to detail
flexible attitude towards work
discipline and regard for confidentiality and security at all times
willingness to travel both within the United Kingdom and abroad to attend
conferences
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The Research Assistant will be encouraged to develop research skills and
interests within the sphere of epigenetics, bioinformatics and systems biology.
He/she will be encouraged to participate in training schemes provided by
Imperial College including the possibility to register for a PhD.
Application Guidance
Please read the person specification carefully and describe, as part of your
application, how much you feel you meet each of the criteria. If you need more
space, please attach additional sheets to the application form.
The recruitment monitoring section of your application will be detached and will
be used only for monitoring and audit purposes as a basis for supporting our
commitment to Equal Opportunities.
An application form and full CV quoting reference number HM2013058 should
be sent online via the Imperial College iRecruitment website.
Short listed candidates will be contacted as soon as possible after the closing
date.
Thank you for your interest in this post. We look forward to receiving your
application.