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IMPERIAL COLLEGE LONDON JOB DESCRIPTION Job Title: Research Associate Section: Investigative Medicine Division: Diabetes, Endocrinology and Metabolism Department: Medicine Job Family: Academic and Research, Level B Salary Range: £26,860 - £39,130 per annum Responsible to: Dr James Gardiner Key Working Relationships (internal): Other academic staff and laboratory staff working with Dr Gardiner within the Departments of Investigative Medicine Section and Molecular Endocrinology Group especially Professor Graham Williams and Drs D Bassett and W Dhillo Key Working Relationships (external): Academic and research staff at other institutes which may collaborate on the project Location: Hammersmith Campus Duration: Fixed-term until 7 December 2011 Purpose of the Post: This post is funded by a BBSRC project grant awarded to the Investigative Medicine Section. The successful applicant will study the role of the hypothalamic thyroid hormone in the regulation of body weight utilising recombinant adeno-associated virus (rAAV). Obesity is a major and increasing healthcare problem in the developed world, accounting for 1000 deaths in the UK per week. Our research has demonstrated that neuropeptides play an important role in the regulation of appetite. The main site regulating appetite in the brain is the hypothalamus which comprises over fifty discrete functional units termed nuclei. We have pioneered the use of rAAV gene transfer combined with stereotactic microinjection to allow manipulation of gene expression to be targeted to specific nuclei. The project will use cutting edge technology and a wide range of cell and molecular biology techniques to examine the role of thyroid hormone in appetite regulation. The applicant will work in the Investigative Medicine Section, Imperial College London, Hammersmith Campus within a group of approximately 100 staff engaged in obesity research. The applicant will also work closely with the members of the Molecular Endocrinology Group in the MRC Clinical Sciences Centre, also located at the Hammersmith Campus of Imperial College. Summary of project The physiological role of thyroid hormones in the regulation of appetite is poorly understood despite their critical importance in the control of metabolism. Recently it has become evident that tissue levels of thyroid hormone are regulated by the balance of local enzymatic activation and inactivation rather than the plasma levels of the hormones. We have recently shown that low doses of thyroid hormone increase food intake without affecting metabolic rate; an effect that is mediated via the ventromedial nucleus (VMN) of the hypothalamus. The proposed studies will establish the physiological role of thyroid hormones in the VMN in regulating food intake. We will utilise three newly developed murine strains. pROSA26D3 rodents have a gene overexpression construct targeted to the ubiquitously expressed endogenous ROSA26 locus. A floxed stop transcription cassette is situated between the ROSA26 promoter and the cDNA encoding type 3 deiodinase (D3), the enzyme responsible for inactivating thyroid hormone, thereby preventing overexpression of the D3 enzyme. These murine will be stereotaxically injected with recombinant adeno-associated virus expressing a Cre-GFP fusion (AAVCre-GFP) into the VMN. This will result in excision of the floxed stop cassette by cre-recombinase and overexpression of D3, resulting in local depletion of thyroid hormones, thereby enabling the physiological consequences of tissue-specific hypothyroidism in the VMN in the regulation of food intake to be established. Two further strains of rodents harbouring floxed alleles of thyroid hormone receptor (TR) alpha or beta will also be used to enable tissue specific deletion of the T3 receptors and comparison of receptor deficiency with hormone deficiency. These studies will characterise the TR isoform responsible for the actions of T3 on the regulation of food intake in the VMN. Key Responsibilities: The Research Associate will be expected to: Design, conduct, evaluate and supervise experimental research independently Prepare manuscripts for publication Keep up-to-date with scientific advances in the field Actively participate in departmental meetings and perform research presentations Mentor and train post-graduate students Provide training and supervision to technical staff Undertake a limited amount of teaching to undergraduates (as necessary) Contribute actively in the management and maintenance of the laboratory including organisation and coordination of in vivo research To comply with relevant College policies, including Financial Regulations, Equal Opportunities Policy, Promoting Race Equality Policy, Health and Safety Policy, Information Systems Security Policy, Intellectual Property Rights and Register of Interests Policies. Additional Duties Presentation of research findings at national and international scientific meetings Any other duties as may be deemed reasonable Job descriptions cannot be exhaustive and so the post holder may be required to undertake other duties, which are broadly in line with the above key responsibilities. The post holder is expected to observe and comply with all College policies and regulations, for example Health and Safety, Data Protection etc. Imperial College is committed to equality of opportunity and to eliminating discrimination. All employees are expected to adhere to the principles set out in our Equal Opportunities in Employment Policy, Promoting Race Equality Policy and Disability Policy and all other relevant guidance/practice frameworks. PERSON SPECIFICATION Applicants are required to demonstrate that they possess the following attributes Education and Qualifications PhD degree (or equivalent professional qualification and experience) in neuroscience, biochemistry, molecular biology, or a related discipline Knowledge and experience Essential Previous in vivo experience In depth knowledge of general molecular biology including PCR, sub-cloning, ELISA, in situ hybridisation and blotting techniques Knowledge of hypothalamic regulatory systems Interest in the physiological control of energy homeostasis Desirable Production and purification of adeno-associated virus or similar virus Previous experience of training staff and students in laboratory techniques Competencies, Skills and Abilities Essential Proven skills in molecular biology and tissue culture techniques A track record of success in a research environment Exceptional organisational and time management skills Excellent written and verbal communication skills, including the ability to write clearly and succinctly for publication Proven ability to work autonomously and show initiative in driving research Ability to prioritise a varied workload and work under pressure to meet deadlines, while maintaining a high level of accuracy Ability to follow protocols and learn new techniques in a concise and skilled manner Ability to work constructively and effectively within a large team Proven ability to relate well to others and form positive working relationships with a wide range of people Adept in the use of computers and searching the relevant databases necessary for the project Knowledge of statistical procedures 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 HM2011097 should be sent, by the closing date of 30 May 2011, online via the Imperial College iRecruitment website. Shortlisted 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.