LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE (University of London) FACULTY OF INFECTIOUS AND TROPICAL DISEASES PATHOGEN MOLECULAR BIOLOGY DEPARTMENT POST-DOCTORAL RESEARCH FELLOW 1. ADVERTISEMENT We are seeking to appoint a post-doctoral Research Fellow The successful applicant will work in Prof David Conway’s research group to study population genetic structure and signatures of selection in the genome of the malaria parasite Plasmodium falciparum sampled from endemic sites in West Africa. This involves collaboration with the National Institute for Public Health Research (INSRP) in Mauritania, and the Wellcome Trust Sanger Institute in the UK, with the work of this post based and primarily conducted at LSHTM. The Research Fellow will conduct multi-locus microsatellite analyses on large number of population samples and whole genome sequence polymorphism analyses on a subset of these populations. Responsibilities range from design and processing of samples for generation of genotypic and sequence data, to statistical analyses of data using new computational tools. The successful applicant may either be excellent in a range of skills covering laboratory and computational analysis, or outstanding in more advanced statistical analysis of population genomic data. For more information on this project, please contact david.conway@lshtm.ac.uk The post is funded by the UK Medical Research Council (MRC) for a period of 3 years and is available from 1st January 2012, until 31st December 2014. Salary is from £35,511 to £39,555, per annum, inclusive. The successful candidate will be placed on the scale according to skills and experience. Applications should be made on-line via our website at http://jobs.lshtm.ac.uk/ The reference for this post is DC1. Online applications will be accepted by the automated system until midnight of the closing date. Applications should also include the names and email contacts of 2 referees who can be contacted immediately if shortlisted. Any queries regarding the application process may be addressed to jobs@lshtm.ac.uk . The London School of Hygiene & Tropical Medicine is committed to being an equal opportunities employer FURTHER PARTICULARS 2. GENERAL INFORMATION The London School of Hygiene & Tropical Medicine The London School of Hygiene & Tropical Medicine is Europe’s leading 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 1400 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, immunologists, ophthalmologists, anthropologists, virologists, pharmacologists and nutritionists. At any one time around 100 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£62.4 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." Faculty of Infectious and Tropical Diseases The Faculty of Infectious and Tropical Diseases encompasses all of the laboratorybased 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 faculty 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 Faculty is organised into four large research departments comprising: Pathogen Molecular Biology, Immunology and Infection, Disease Control, and Clinical Research. There is close interaction between scientists in different research teams. The Faculty 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). Department of Immunology and Infection (Head: Professor Eleanor Riley) Research in the Department of Immunology and Infection 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); using anti-malarial antibodies as a marker of malaria exposure & assessment of the use of sero-epidemiology to monitor and target malaria control measures www.seromap.com (C. Drakeley)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) Department of Pathogen Molecular Biology (Head: Professor John Kelly) Research in the Department of Pathogen Molecular Biology 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. PMBD 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 PMBD 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 Department 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. Department of Clinical Research (Head: Prof Alison Grant) The Department of Clinical Research 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 Department, and currently supports five Clinical Training Fellows and two Career Development Fellows, most of whom are based overseas. Much of the Department’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. Department of Disease Control (Head: Dr Mark Rowland) This multidisciplinary Department 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 Department’s Environmental Health Group, which plays a leadership role in research and operational support for hygiene promotion, water supply and sanitation. The Department 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 the Malaria Capacity Development Consortium (MCDC). The Department’s valuable mosquito colonies are used for testing repellent products and insecticides in the laboratory. The Department 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 Faculty 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 Department of Immunology and Infection. In addition, the Faculty 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. Project information Appropriate development of antimalarial vaccines and drugs needs to be informed by an understanding of processes of adaptation of malaria parasites in endemic populations. We will investigate population genetic structure and phenotypes of P. falciparum under selection at the north western extreme of its African range in Mauritania where endemicity persists despite limited and highly seasonal rainfall that restricts transmission. We predict that, compared with countries to the south that we recently studied, genetic divergence between populations of P. falciparum in different areas of Mauritania will be high due to genetic drift with small effective population sizes, and restricted gene flow among endemic foci. This will be investigated by conventional microsatellite analyses and whole genome sequence polymorphism analyses. We also predict that the selective landscape will be strikingly different from elsewhere, leading to measurable effects including the following: (i) a low level of acquired immunity in the human population will reduce diversifying selection on merozoite invasion ligands so these will be less diverse and highly skewed towards the use of a particular preferred primary ligand, which we can test using culture assays; (ii) alleles under strong positive selection will increase to high frequencies in local populations before sporadic gene flow events allow them to spread so there will be major local differences in drug resistance. Understanding these processes in terms of demographic and selective constraints on the parasite will guide targeting of existing control tools including antimalarial drugs and development of new tools including vaccines. Genome sequencing of population samples of parasites from Nouakchott, and other selected locations among those sampled in Mauritania, will allow tests to identify loci under directional selection, in analyses comparing with other West African parasite population genomic data. 3. JOB DESCRIPTION Post: Research Fellow Grade: 6 Responsible to: Professor David Conway Department: Pathogen Molecular Biology Main duties and responsibilities: To work closely with collaborators based at INSRP in Mauritania sampling P. falciparum isolates from five endemic sites in the country, by giving advice and support remotely from London and in one or two collaborative visits to INSRP. To be responsible for generating parasite genotype results including multi-locus microsatellite characterisation of the local populations, and leading the statistical analysis of population genetic structure and differentiation evident in these data To lead the preparation of parasite genomic material from clinical samples for sequencing, and the statistical analyses of genome variation data to identify signatures of natural selection and unusual population structure affecting particular genomic regions To be critically involved in development and evaluation of hypotheses on mechanisms of natural selection and non-equilibrium population structure in malaria parasites To complete and write up excellent research output for timely publication To collaborate with the Wellcome Trust Sanger Institute Malaria Programme on approaches to programming and data sharing in analysis of parasite population genomics To work actively to train and empower research colleagues at INSRP and other collaborators in endemic countries, working with other members of LSHTM and the Wellcome Trust Sanger Institute to help develop the parasite population genetics field To contribute to the Faculty teaching programme, 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). 4. PERSON SPECIFICATION Essential: PhD in genetical or statistical sciences Evidence of high quality and consistent research productivity including excellent publications Solid successful experience in analysis of complex data sets including genomic-scale or population genetic data Ability to work very effectively in interaction with others of different backgrounds within a research team and in collaboration across institutes Desirable: Strong and demonstrably productive personal experience in laboratory research and/or working with laboratory scientists in study design and data analysis Experience in infectious disease research Experience or interest in epidemiology Considerable experience in computer programming Strong ability in scientific communication including writing and personal presentation 5. SALARY AND CONDITIONS OF APPOINTMENT The post is funded by UK Medical Research Council (MRC) for a period of 3 years and is available from 1st January 2012 until 31st December 2014. Salary is from £35,511 to £39,555, per annum inclusive. 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". 6. APPLICATIONS Applications should be made on-line via our website at http://jobs.lshtm.ac.uk The reference for this post is DC1. 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 the names and email contacts of 2 referees who can be contacted immediately if shortlisted. Any queries regarding the application process may be addressed to jobs@lshtm.ac.uk. 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.