JOB DESCRIPTION
Post Title:
Research Associate
Institute:
National Heart and Lung Institute
Section:
Vascular Science
Job Family:
Academic and Research, Level B
Salary Range:
£33,140 - £36,130 per annum
Responsible To:
Professor Justin Mason
Works Closely With:
Professor Justin Mason and Professor Anna Randi
Key Working Relationships:
Internal:
Professor Mason's research group
External:
Mr Prakash Punjabi, Cardiothoracic Surgery
Contract:
Full-time and fixed-term for 36 months
Location:
Hammersmith Campus
Research Programme
Title: PKCε-dependent activation of NF-κB signalling selectively promotes vascular
endothelial protection.
The present post is funded for 36 months by a project grant from the British Heart
Foundation. We have established an important role for PKCε in endothelial homeostasis and
specifically cell survival, resistance to injury and inflammation (1,2). A key factor in our
understanding has been the observation that PKCε activation selectively modulates NF-κB
transcriptional responses to induce cytoprotective genes, while suppressing proinflammatory
pathways. Using a cell molecular and in vivo approach, we now propose to identify the
molecular mechanisms underlying selective targeting of NF-κB cytoprotective transcripts. A
key aim will be to determine the influence of shear stress patterns on the activation of PKCε
and NF-κB, and the subsequent induction of protective genes. Analyses will include
investigation of post-translational modifications and epigenetic mechanisms, the study of
physiological PKCε agonists and novel PKCε targets including CREB-1 and Nrf2, and
demonstration of the functional importance of PKCε-NF-κB signalling in the vascular
endothelium in vivo. Ultimately, the value of targeting PKCε therapeutically will be
determined by understanding its associated signalling pathways. We anticipate that this
approach will eventually lead to identification of optimal targets and novel therapeutics for
vascular inflammation, endothelial dysfunction and atherosclerosis.
1. A PKCε/Akt signalling complex protects human vascular endothelial cells against apoptosis through
induction of Bcl-2. R Steinberg, OA Harari, EA Lidington, et al. J Biol Chem . 2007 282:32288-32297.
2. Protein kinase Cε activity induces anti-inflammatory and anti-apoptotic genes via an ERK1/2 and
NF-κB-dependent pathway to enhance vascular protection. O Dumont, H Mylroie, A Sperone, A
Bauer, et al. Biochem J 2012; 447:193-204
Job Summary
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To complete the aims of the project:
o To define the molecular mechanisms that specifically favour the induction of
cytoprotective genes following PKCε-mediated NF-κB activation, using a gain
and loss of function approach.
o Determine the ability of physiological ligands of PKCε to activate these
signalling pathways and induce protective genes, and to establish the
influence of LSS and DF on these responses.
o Using in vitro and in vivo molecular targeting, determine the functional
importance of the relationship between PKCε, NF-κB and vasculoprotective
genes, for both endothelial homeostasis and resistance to injury, comparing
sites protected from atherosclerosis, with those susceptible to it.
To contribute to the scientific direction of the project, with a gradual increase in
responsibility and autonomy in the design and the overall strategy of the project
To manage the collaboration with Prof Randi and Mr Punjabi
To perform experiments in the laboratory, analyse and interpret data and keep
detailed records of experimental procedures and results
To undertake project management and/or supervise junior members of the team
To submit publications to peer-reviewed journals and to contribute to efforts to attract
external research funding
To participate in and present data at national and international conferences
To share responsibility for the operation and organisation of laboratory facilities,
under the direction of senior academic staff and the laboratory manager; attend and
contribute to laboratory management and safety meetings
Research Duties
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To work in a collaborative, collegiate manner within the research team and Unit.
To conduct and plan own scientific work with appropriate supervision
To identify and develop suitable techniques, and apparatus, for the collection and
analysis of data
To conduct data analysis, ensure the validity and reliability of data and to maintain
highly organised and accurate records of all experimental work
To participate in weekly research-in-progress meetings and departmental seminars
To write reports for submission to research sponsors
To attend relevant meetings, workshops and conferences to present findings and
develop scientific training and skills
To submit publications to high-quality peer-reviewed journals
To actively participate in the research programme of the Group, Unit and Division
Provide training, advice and supervision to junior research staff, PhD, MSc and BSc
students, as dictated by the varying needs of the department
To contribute to the smooth running of the Group/Unit’s laboratories and facilities with
other scientists, clinicians, technicians and students within the laboratories
To promote the reputation of the Group, the Department, Division and the College
To contribute to bids for research grants
To develop contacts and research collaborations within the College and the wider
scientific community
To comply with the College, Division, and Unit safety practices and to attend courses
on safety when appropriate
Any other duties as may be deemed reasonable by Head of Group as well as Head of
Division/Department/Section
Other Duties
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To undertake appropriate administration tasks
To attend relevant meetings
To undertake any necessary training and/or development
To monitor reports on budget information every three months
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.
IMPERIAL COLLEGE LONDON
PERSON SPECIFICATION
Qualifications
Essential
 PhD or equivalent qualification, or equivalent research, industrial or commercial
experience, in a relevant biological discipline such as molecular or cellular biology
Knowledge and Experience
Essential
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Desirable
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Proven experience of vascular biology
Proven experience in cellular and molecular biology
Experience in the use of in vivo and in vitro models of inflammation
Basic knowledge of statistics and bioinformatics
Practical experience within a research environment and/or publication in relevant
peer-reviewed journals
Experience of working well as part of a team
Ability to prioritise a varied workload and work under pressure to meet deadlines
while maintaining a high level of accuracy
Good knowledge of endothelial biology
Experience in the use of confocal microscopy
Good knowledge of signalling pathways including NF-κB.
Experience in the study and analysis of endothelial shear stress
Experience in biochemistry
Skills and Abilities
Essential
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Ability to conduct a detailed review of recent literature
Ability to change and adapt according to the development of the project
Ability to develop and apply new concepts
Creative approach to problem-solving
Proven organisational skills
Excellent verbal communication and the ability to deal with a wide range of people
Excellent written communication and the ability to write clearly and succinctly for
publication
Ability to work within in a team and to respect and collaborate with colleagues
Ability to direct the work of a small research team and motivate others to produce
a high standard of work
Ability to organise own work with minimal supervision
Ability to prioritise own work in response to deadlines
Thoroughness and ability to keep accurate records
Ability to exercise initiative and work independently
Advanced computer skills, including word-processing, spreadsheets and the
Internet
Other
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Self-motivation
Willingness to work as part of a team and to be open-minded and cooperative
Flexible attitude towards work
Discipline and regard for safety at work, confidentiality and security at all times
Willingness to undertake any necessary training for the role
Willingness to travel both within the United Kingdom and abroad to conduct
research and attend conferences
Willingness to teach and supervise BSc, MSc and PhD students
Willingness to work out of normal working hours (including weekends) if the
requirements of the project demand