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LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE (University of London) DEPARTMENT OF INFECTIOUS AND TROPICAL DISEASES IMMUNOLOGY UNIT Research Fellow – Pharmacokinetics with Pharmidex Ltd., Harrow 1. ADVERTISEMENT Research Fellow - Pharmacokinetics We are seeking to appoint a Research Fellow to work on a Bill & Melinda Gates Foundation funded project, joint with the University of Glasgow, to develop in vivo imaging techniques to study drug efficacy, pharmacology and pathogenesis in human African Trypanosomiasis. The successful applicant will hold a PhD in pharmacology or other closely related biological subjects or have experience in industry. Appropriate research experience in infectious disease agents and models would be an advantage. The post requires an individual with a meticulous approach to data recording, an ability to manage their own workload and good team working skills. This post will be based at the London School but will involve significant periods working with Pharmidex Ltd. in Harrow. This full time post is funded by the Bill & Melinda Gates Foundation for a period of 2 ½ years and is available from 1st June 2010. Salary is on the Academic Pathway Grade 6 scale at £35,370 per annum (inclusive of London Weighting). Applications should be made on-line via our website at jobs.lshtm.ac.uk. The closing date is Thursday 6 May 2010 and the reference for this post is SC02. Online applications will be accepted by the automated system until midnight of the closing date. Any queries regarding the application process may be addressed to [email protected] or via telephone number 0207 927 2201. The supporting statement section should set out how your qualifications, experience and training meet each of the selection criteria. Please provide one or more paragraphs addressing each criterion. The supporting statement is an essential part of the selection process and thus a failure to provide this information will mean that the application will not be considered. An answer to any of the criteria such as “Please see attached CV” will not be considered acceptable. Please note that if you are shortlisted and are unable to attend on the interview date it may not be possible to offer you an alternative date. The London School of Hygiene & Tropical Medicine is committed to being an equal opportunities employer 2. GENERAL INFORMATION The London School of Hygiene & Tropical Medicine The London School of Hygiene & Tropical Medicine is Britain's national school of public health and a leading postgraduate institution worldwide for research and postgraduate education in global health. Part of the University of London, the London School is the largest institution of its kind in Europe with a remarkable depth and breadth of expertise encompassing many disciplines. The School was ranked one of the top 3 research institutions in the country in the Times Higher Education’s 'table of excellence', which is based on the 2008 Research Assessment Exercise (RAE), ahead of the London School of Economics, Oxford, Imperial and University College, London. The institution also achieved the largest increase in ranking compared with 2001, of any of the top 10 institutions in the RAE rankings. In 2009, the School became the first UK institution to win the Gates Award for Global Health. The School’s environment is a rich multicultural one: there are almost 4000 students from 100+ countries following 22 taught masters courses delivered either in London (~650) or through distance learning (~2700), and undertaking research degree training (~400). Over 40% of these students are from non-European countries. The largest growth has been in distance learning students (>40% over 3 years), though the London-based student population (where accommodation limits growth) is at its highest level ever. Alumni are working in more than 180 countries. The School has about 1300 staff drawn from over 60 nationalities. There are research collaborations with over 100 countries throughout the world, utilizing our critical mass of multidisciplinary expertise which includes clinicians, epidemiologists, statisticians, social scientists, molecular biologists and immunologists. At any one time around 80 School staff are based overseas, particularly in Africa and Asia. We have a strong commitment to partnership with institutions in low and middle income countries to support the development of teaching and research capacity. The School has expanded greatly in recent years. Its research funding now exceeds m£60 per annum, much of it from highly competitive national and international sources. The commitment of staff to methodological rigour, innovative thinking and policy relevance will ensure that the School continues to occupy a leadership position in national and global health, adapting quickly to new challenges and opportunities. Mission The School's mission is to contribute to the improvement of health worldwide through the pursuit of excellence in research, postgraduate teaching and advanced training in national and international public health and tropical medicine, and through informing policy and practice in these areas." Department of Infectious and Tropical Diseases The Department of Infectious and Tropical Diseases encompasses all of the laboratory-based research in the School as well as that on the clinical and epidemiological aspects of infectious and tropical diseases. It is headed by Simon Croft, who is Professor of Parasitology. The range of disciplines represented in the department is very broad and inter-disciplinary research is a feature of much of our activity. The spectrum of diseases studied is wide and there are major research groups with a focus on malaria, tuberculosis, HIV/AIDS and other sexually transmitted diseases, vaccine development and evaluation, and vector biology and disease control. The Department is organised into four large research units comprising: Pathogen Molecular Biology, Immunology, Disease Control and Vector Biology, and Clinical Research. There is close interaction between scientists in different research teams. The Department has strong overseas links, which provide a basis for field studies and international collaborations in developed and developing countries. The teaching programme includes MSc courses, taught in-house and by distance learning, which are modular in structure, a variety of short-courses and an active doctoral programme (PhD and DrPH). Immunology Unit (Head: Professor Eleanor Riley) Research in the Immunology Unit centres on analysis of the host response to infection at the molecular, cellular and population levels. The goals are to develop a greater understanding of basic mechanisms of immunological protection versus pathology, and to apply this knowledge to the development of immunological interventions and the identification of correlates of immune status. Our work involves application of state-of-the-art cellular and molecular approaches to the in vitro analysis of pathogen-host cell interactions, to in vivo studies in models and to the study of immunity at the population level in disease endemic areas. Main areas of research include the regulation of acute and chronic inflammation; macrophagepathogen interactions; cellular pharmacology; the production of cytokines during innate and acquired immune responses; T-cell function and antigen recognition; the mechanisms of immunopathology; the development of vaccines; and delivery systems for vaccines and drugs. Current research includes the role of acute phase proteins in resistance to infection, homeostasis and inflammatory disease, mechanisms of macrophage activation, control of cytokine synthesis and mammalian lectin interactions (J. Raynes); intracellular trafficking and secretory pathways of cells of the immune system (T. Ward); the role of innate responses in resistance to the bacterial pathogens, Mycobacterium tuberculosis and Burkholderia pseudomallei, activity and regulation of natural killer cells and their effect on macrophage activation and recruitment, regulation of chemokine receptors during infection and granulomatous tissue responses in the lung against Cryptococcus neoformans and Mycobacterium tuberculosis (G. Bancroft); correlates of protection against tuberculosis and studies of BCG vaccination, human CD8+ T-cell responses to mycobacterial antigens and synthetic peptides, use of whole blood assays in immuno-epidemiology (H. Dockrell); cytokine and chemokine responses to leprosy, cellular composition and effects of steroids on skin and nerve lesions of reactional leprosy, identification of specific peptides for immunodiagnosis of leprosy (S. Young); innate and adaptive immunity to malaria including activation of natural killer cells, cytokine regulation in clinical immunity and immunopathology, regulation of antibody production and immunoglobulin class switching (E. Riley); transmission of Plasmodium falciparum malaria including antibody responses to gametocyte-infected erythrocyte surface antigens, effect of gamete antigen variability on transmission, gametocyte sequestration and development and gametocyticidal drug therapy (C. Sutherland); characterisation of protective immune mechanisms and defined antigens in attenuated vaccine models of schistosomiasis (Q. Bickle); impact of concomitant viral, bacterial, protozoal and helminth infections on induction of immune responses and immunopathology and T cell regulation and induction of mucosal immune responses during intestinal nematode infections (H. Helmby); the identification and evaluation of novel drugs and drug delivery systems for leishmaniasis, trypanosomiasis and malaria, interaction between antiprotozoal drugs and the immune response (L. Vivas, V. Yardley) Pathogen Molecular Biology Unit (Head: Professor Brendan Wren) Research in the PMB Unit focuses on the molecular biology and genetics of pathogens and their hosts in the context of improving the understanding and control of infectious diseases. Aspects of pathogen biology of interest include: (i) determining the mechanisms of infection of globally important viral, bacterial and parasitic pathogens; (ii) deciphering the genetic diversity of selected disease agents in natural populations and to determine its epidemiological impact, (iii) studying immune evasion mechanisms of particular disease agents, (iv) exploiting parasitic, bacterial and viral pathogens as model biological systems and (v) developing practical applications including improved diagnostic tests and the identification and characterisation of vaccine candidates and drug targets. PMBU currently has funding to investigate, amongst others, the malaria parasite (Plasmodium spp), Chagas disease (Trypanosoma cruzi), African sleeping sickness (Trypanosoma brucei), amoebic dysentery (Entamoeba), the Leishmania species, bacterial food borne pathogens (Campylobacter jejuni and Yersinia enterocolitica), gastric ulcers/cancer (Helicobacter pylori), pseudomembranous colitis (Clostridium difficile), plague (Yersinia pestis), paddy field melioidosis (Burkholderia pseudomallei), Tuberculosis (Mycobacterium tuberculosis), Pneumonia (Streptococcus pneumoniae), Bluetongue viral disease of livestock, Herpesviridae, SARS, the hemorrhagic fever virus (RVFV) and the enteric rotavirus that cause significant diarrhoeal disease in infants developing countries. The long-term aim of PMBU research is to gain a fully rounded understanding of the complex and dynamic ways by which pathogens modulate virulence and interact with the human host. Such a holistic approach will vastly increase the scope for the rational of design of long-term intervention strategies to reduce the burden of infectious disease. In recent years such a mission has been significantly enhanced by the availability of whole genome sequences. Members of the Unit are, or have been, involved in several pathogen genome projects including Herpes, Campylobacter jejuni, Yersinia pestis, Clostridium difficile, Entamoeba and Trypanosome species. In particular, post genome studies have facilitated research on more complex parasites such as Plasmodium, Entamoeba and Trypanosome species. The interpretation and exploitation of this basic information is the platform for numerous new avenues of research on pathogenesis, epidemiology and the evolution of virulence. Clinical Research Unit (Head: Dr Alison Grant) The Clinical Research Unit addresses infectious diseases of major public health importance in developing countries. Activities include trials of new therapies, vaccines and educational interventions; the development of new diagnostic tests; studies to elucidate the immunological and molecular correlates of pathogenesis and protective immunity, and to identify genetic polymorphisms conferring protection or susceptibility to infectious diseases; health services research which aims to identify the most efficient and cost-effective way to deliver health care; and health policy analysis. In addition to our many overseas collaborations, we have close links with the Hospital for Tropical Diseases, in new, purpose-built accommodation on the main UCL Hospital campus, five minutes walk from the School. The Wellcome Trust Bloomsbury Centre for Clinical Tropical Medicine is based in the Unit, and currently supports five Clinical Training Fellows and two Career Development Fellows, most of whom are based overseas. Much of the Unit's research concerns HIV and related infections; in particular, the interaction between HIV infection and other sexually transmitted diseases, and between HIV infection and tuberculosis. We have longstanding and fruitful collaborations addressing these issues in Tanzania, Zambia, Uganda and South Africa. Brian Greenwood FRS is leading an initiative to strengthen malaria research in the School through new collaborative links in Africa. Research and teaching on blinding diseases in developing countries has been greatly strengthened by the recruitment of Allen Foster, who is Medical Director of CBM International, an NGO with programmes for the prevention of blindness and disability in over 100 countries; our research on trachoma has played an important part in framing the strategies adopted by the WHO and the new International Trachoma Initiative for the elimination of blinding trachoma by the year 2020. Disease Control and Vector Biology Unit (Head: Professor Daniel Chandramohan) This multidisciplinary Unit includes epidemiologists, entomologists, anthropologists and social scientists, clinical scientists, public health engineers, and geographers. This range of expertise provides us with a battery of tools for focusing on the control of diseases that are insect-borne, water-borne or associated with poor hygiene – mostly in developing countries. Much of the research can be categorised as: evaluating disease control interventions; investigating implementation strategies including working with the private sector; understanding the factors underlying household behaviour in relation to family health; or determining how control resources can be targeted most efficiently. Particular attention is paid to research directed at current health policy issues, including the gap between policy and practice. The DFID Resource Centre for Water and Environmental Health (WELL) and the Hygiene Centre make up the Unit's Environmental Health Group, which plays a leadership role in research and operational support for hygiene promotion, water supply and sanitation. The Unit also houses the largest research group in LSHTM working on malaria control, including the DIFD Team for Applied Research to Generate Effective Tools and Strategies for communicable disease control (TARGETs) and many staff in the Gates Malaria Partnership. The Unit’s valuable mosquito colonies are used for testing repellent products and insecticides in the laboratory. The Unit also includes a major grouping of researchers using spatial analysis in public health. Teaching The School offers 22 one year full-time taught courses leading to the Master of Science (MSc) degree of the University of London and the Diploma of the London School of Hygiene and Tropical Medicine (DLSHTM). The Department of Infectious and Tropical Diseases runs or contributes substantially to ten of these courses and the “Immunology of Infectious Diseases” course is run from within the Immunology Unit. In addition, the Department is responsible for the three-month Diploma in Tropical Medicine and Hygiene (DTM&H) and offers a range of specialist short courses lasting usually one or two weeks. Three MSc courses are also offered by Distance-based Learning, including one on Infectious Diseases. Research Training The School offers two doctoral training programmes. The MPhil/PhD degrees are designed for those who wish to go on to a full time research career. The DrPH is directed towards those who expect their careers to be more in the practice of public health. Research Management and Teaching Training The School offers an extensive staff training programme which the appointee will be encouraged to use. Project information Human African trypanosomiasis, also known as sleeping sickness, is a disease of the world’s poorest populations in sub-Saharan Africa where 60 million people, in 36 countries, are at risk. In order to treat late-stage African trypanosomiasis, when trypanosomes have penetrated the brain and other organs, drugs must cross barriers, including the blood brain barrier, in levels sufficient to kill parasites. In this project, we propose to develop new models to monitor drug activity using in vivo imaging systems and to determine pharmacokinetic and pharmacodynamic properties of trypanocidal molecules in the CNS. The ultimate aim is to provide models to expedite screening of new chemicals against late-stage African trypanosomiasis. The project is funded by the Bill & Melinda Gates Foundation and is a collaborative venture between Glasgow University and the LSHTM. The goal of this postdoctoral position is to develop pharmacokinetic and pharmacodynamic methods to determine the distribution and levels of antitrypanosomal drugs in the CNS of experimental model systems of Trypanosoma b. brucei and T. b. gambiense, and to relate this information to parasite distribution (based upon imaging) and parasite drug sensitivity. The appointee will have a lead role in developing the model. She or he will be based at LSHTM and will be working on the project in partnership with Pharmidex (Northwick Park, London) where the appointee will also be involved in extensive studies. They will also interact with other members of the team involved in imaging parasite distribution and CNS changes both at LSHTM and the University of Glasgow. Pharmidex Pharmidex delivers world-leading CNS and ADMET solutions to support preclinical drug discovery and development in CNS and other disease areas. The company’s drug-discovery and development solutions fall into three key areas: CNS drugdiscovery and delivery solutions; ADMET, PK and bioanalytical solutions; and collaboration and consultancy. Pharmidex is unique in its focus on central nervous system (CNS) drug-discovery and development services, and has world-leading expertise and technologies in this field. It is the only company in the world offering direct assessment of brain penetrability and free concentration of compounds in extracellular fluid (NeuroPK® and NeuroPD™) as a service to CNS R&D departments. This is achieved through the company’s innovative screens and patented technologies and underpinned by the ability to integrate neuroscience, DMPK and CNS drug discovery expertise. Today the company has diversified to provide a wider range of platform technologies, including in vitro and in vivo absorption, distribution, metabolism and excretion (ADME), pharmacokinetics, bioanalysis, safety pharmacology, in vitro pharmacology, and efficacy and safety studies. The knowledge and experience of the staff at Pharmidex, combined with its costeffective platform technologies and high-quality data, can help to move drugdevelopment programs quickly and cost-effectively through preclinical development. This can be through collaborations, under a shared risk–shared reward model or on a consultancy basis. Pharmidex has successfully participated in European projects: FP6 (InnoMEd – Innovative Medicines for Europe, Project number LSHB-CT-2005-518170, an integrated life project with 43 partners across Europe for identification of Biomarkers for Alzheimer disease) and FP7. Pharmidex has also been successful in winning the “Service company of the year” award in 2005 from UK Trade and Investment for exquisite delivery of high tech solutions to pharmaceutical and biotechnology companies globally as well as being nominated for the “best new exporter” international business award in same year. Objectives of this project: (i) (ii) (iii) To develop methodologies to determine the distribution and levels of antitrypanosomal drugs in the CNS during infection To develop improved models to measure pharmacodynamic characteristics of anti-trypanosomal drugs To relate the pharmacokinetic and pharmacodynamic data to that derived by the imaging team and pathogenesis teams to develop a predictive model 3. JOB DESCRIPTION Post: Research Fellow - Pharmacokinetics Grade: Academic Pathway Grade 6 Responsible to: Prof Simon Croft (LSHTM) and Dr Mo Alajeveh (Pharmidex) (Workpackage Leaders) Unit: Immunology / Pharmidex Ltd. Start date: approx. 1st June 2010 Main duties and responsibilities: in partnership with the lead investigators, carry out original research in pharmacology of anti-trypanosomal drugs in line with the project objectives, including the development of a new predictive model for future drug development projects. This will require expertise in pharmacokinetics and an ability to learn imaging technologies and understand infectious disease pathogenesis; collate and analyse research data and prepare it for monthly reports, regular presentation to partners and publication; author sections of annual reports and publications, input to web site; lead and manage the day-to-day running of the designated section of the research project, provide the close liaison between LSHTM and Pharmidex, and contribute to other appropriate research activities as they arise; attend and contribute to weekly laboratory meetings, journal clubs, unit seminars, conferences and other academic gatherings; contribute to the School’s MSc and Departmental teaching programmes through participation in lectures, practical classes, student supervision or tutorials, as directed. This to involve up to 10% of your time per annum, subject to the policy of any funding agency (by agreement, some staff may make a greater contribution than this); any other duties as assigned by the lead investigators, Unit Head and Head of Department. 4. PERSON SPECIFICATION The following are essential: A PhD and/or proven experience in industry, in a pharmacology or related biomedical area, with experience in infectious diseases being an advantage Proven experience in pharmacokinetic techniques and methodologies Experience of working with in vivo models An excellent and meticulous approach to recording of data, protocols and daily activities Ability to manage a research project Ability to work as part of a team A flexible approach to working hours Advanced computer literacy Excellent communication skills and an ability to develop those skills in a multicultural environment The following would be desirable: Experience in culture of pathogenic microorganisms Experience in imaging methodologies UK Home Office License for studies involving rodents Peer-reviewed publications 5. SALARY AND CONDITIONS OF APPOINTMENT The full time post is funded by the Bill & Melinda Gates Foundation for a period of 2½ years and is available from 1st June 2010. Salary is on the Academic Pathway Salary scale Grade 6 at £35,370 per annum (inclusive of London Weighting). Annual leave entitlement is 30 working days per year for all staff (pro-rata for part-time staff). In addition to this there are 6 fixed-date "Director's Days". The post will be subject to the LSHTM terms and conditions of service. Membership of the USS pension scheme is available. The School's retirement date is 30 September following the 65th birthday. It is the School's policy not to appoint candidates aged 65 or over. The successful candidate, as appropriate, would be able to register for a PhD at the School part-time. A pension scheme and interest free season ticket loan are available. The School is conveniently situated for public transport (Goodge Street, Russell Square, Euston Square and Tottenham Court Road tube stations nearby). The School has a restaurant, bar and common room. The School has a no smoking policy and an Equal Opportunities Policy. 6. APPLICATIONS Applications for this post should be made online at our website http://jobs.lshtm.ac.uk. The reference for this post is SC02. Online applications will be accepted by the automated system until midnight of the closing date. In the online system, applicants should complete all sections. The supporting statement section should set out how your qualifications, experience and training meet each of the selection criteria. Please provide one or more paragraphs addressing each criterion. The supporting statement is an essential part of the selection process and thus a failure to provide this information will mean that the application will not be considered. An answer to any of the criteria such as “Please see attached CV” will not be considered acceptable. Applications should also include a curriculum vitae, a covering letter and the names and email addresses of two professional referees who may be approached immediately, one of whom should be a recent employer or academic supervisor. Any queries regarding the application process may be addressed to [email protected] or telephone 020 7927 2201, quoting the job reference number SC02. Closing date for receipt of applications in Thursday 6 May 2010 Interviews will be held in week commencing 17 May 2010. Please note that if you are shortlisted and are unable to attend on the interview date it may not be possible to offer you an alternative date. The London School of Hygiene & Tropical Medicine is committed to being an equal opportunities employer