Imperial College London Job Description Job Title: Research Associate Department: Experimental Medicine and Toxicology Division: Investigative Science Job Family and Level: Research and Education, Level B Salary Range: £26,720 - £30,520 per annum Responsible To: Dr Beata Wojciak-Stothard Professor Martin Wilkins Works Closely With: Dr Beata Wojciak-Stothard (Experimental Medicine and Toxicology) Dr James Leiper (MRC Unit, Imperial College) Funding: BHF Location: Burlington Danes Building, Hammersmith Campus Duration: Fixed-term for three years Project Title: The role of ADMA in the regulation of pulmonary endothelial cell-to-cell communication and endothelial permeability. Experimental Medicine & Toxicology The Department of Experimental Medicine & Toxicology is an active research department that comprises a number of research groups specialising in toxicology, proteomics, apoptosis, and pulmonary hypertension. Detailed Project Lack of nitric oxide, breakdown in pulmonary endothelial barrier function and abnormal cell-to-cell communication are features of endothelial dysfunction in PH. Endogenously produced nitric oxide synthase inhibitor, asymmetric methylarginine (ADMA) increases pulmonary vascular leakage in vitro and in vivo. We hypothesize that ADMA metabolism regulates pulmonary endothelial barrier function via modulation of intercellular gap junctional communication. Using heterozygous or endothelium- specific knockout of genes regulating metabolism of methylarginines, the project aims to establish the effects ADMA metabolism on local endothelial gap junctional conductivity and endothelial permeability in vitro and in vivo and characterise signalling mediators involved. Gap junctional communication will be studied with the use of Fluorescence-activated Cell Sorter (FACS) analysis and confocal microscopy techniques including Fluorescence Recovery After Photobleaching (FRAP). The role of individual connexins and Rho GTPases will be studied with the use of retroviral and adenoviral gene transfer. Research Duties To conduct and plan own scientific work with appropriate supervision in particular undertaking the following: o o o o Culture and treat pulmonary endothelial cells (human and in vivo models) with NOS inhibitors/activators Use viral gene transfer and transfection techniques to investigate the role of enzymes metabolising ADMA (DDAH), individual connexins and signalling mediators including Rho GTPases Study changes in endothelial permeability and gap junctional communication using fluorescent confocal microscopy, FRAP, FACS in cultured cells and whole vessels Compare and contrast data derived from different treatments To maintain highly organised, full, accurate, complete and legible records of experimental work To take initiatives in the planning of research and assisting in the supervision of undergraduate and postgraduate research students and research assistants as required To help write reports for submission to research sponsor In discussion with the other investigators, to prepare work for presentation at appropriate national or international meetings and for publication in relevant peer-reviewed journals To actively participate in the research programme of the Group and Unit including attending and presenting at Group/Unit research meetings and internal seminars To collaborate with other allied scientists within Imperial College and elsewhere in London, the UK or abroad, as appropriate and work with scientists, clinicians, technicians and students within the laboratories Other Duties To contribute and show leadership in the routine running of the laboratory in terms of safety, laboratory maintenance, ordering, and dealing with hazardous material To comply with the College, Division, and Unit safety practices and to attend courses on safety or when appropriate To undertake any appropriate administration tasks designated 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 Any other duties as may be deemed reasonable by Head of group as well as Head of Division/Department/Section 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 Qualifications and Experience Essential PhD in cell/molecular biology or other relevant biological sciences speciality Experience in cell culture, transfection techniques Practical experience in DNA/RNA handling, extraction, PCR, gel electrophoresis Practical experience in protein analysis including SDS-polyacylamide gel electrophoresis and Western Blotting Practical experience in immunofluorescence and confocal microscopy Desirable Experience of work in the field of vascular biology/pulmonary endothelial function Experience in the culture of primary cells from humans and animals Previous experience of work with FACS and FRAP techniques Skills and Abilities Excellent research skills in basic cell/molecular biology techniques Excellent verbal communication skills and the ability to deal with a wide range of people including scientists, sponsors, clinicians and students Computer literate with a good knowledge of different computer programs with experience in data presentation and statistical analyses Ability to conduct a detailed review of recent literature Ability to develop and apply new concepts with a creative approach to problem-solving Excellent written communication skills and the ability to write clearly and succinctly for publication Ability to organise own work with minimal supervision and to prioritise own work in response to deadlines Personal Attributes Willingness to undertake training, specifically with regard to the use of FRAP Willingness to work as part of a team and to be open-minded and cooperative Flexible attitude towards work Willingness to work out of normal working hours (including weekends) if the requirements of the project demand it is also necessary Discipline and regard for confidentiality and security at all times Willingness to travel both within the United Kingdom and abroad to conduct research and/or attend conferences 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 HM2009092 should be sent, by the closing date of 9 November 2009, online via the Imperial College iRecruitment website. Short listed candidates will be contacted as soon as possible after the closing date. If you have any further queries, please telephone 020 8383 4575. Thank you for your interest in this post. We look forward to receiving your application.