LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE (University of London) FACULTY OF INFECTIOUS AND TROPICAL DISEASES PATHOGEN MOLECULAR BIOLOGY DEPARTMENT Research Fellow in Population Genomics We are seeking to appoint a post-doctoral Research Fellow in Population Genomics. The successful applicant will conduct research on population genetic structure and signatures of selection in the genome of the malaria parasite Plasmodium falciparum sampled from endemic sites in West Africa, including The Gambia, Senegal, Mali and Ghana. This is a strategic part of a research programme supported by an ERC Advanced Award to Professor David Conway. The research will involve collaboration with several research groups in West Africa, and the Wellcome Trust Sanger Institute in the UK, while the post is based in London at LSHTM. Responsibilities range from design and support of sample collection for generation of genotypic and sequence data, to statistical analyses of data using new computational tools. The ideal applicant will be excellent in a range of computational analysis skills, with exceptional promise for conducting advanced statistical analysis of population genomic data. This full time post post is funded by the European Research Council (ERC) until 30th June 2017 and is available from 1st October 2012. Salary is on the Academic Pathway scale from £35,661 to £40,499 per annum, inclusive. Applications should be made on-line via our website at http://jobs.lshtm.ac.uk. Online applications will be accepted by the automated system until midnight of the closing date. The reference for this post is DC-ERC1. Any queries regarding the application process may be addressed to jobs@lshtm.ac.uk. Closing date for the receipt of applications is 21 September 2012. The London School of Hygiene & Tropical Medicine is committed to being an equal opportunities employer FURTHER PARTICULARS THE SCHOOL The London School of Hygiene & Tropical Medicine is one of Europe’s leading schools 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). 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 1500 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, economists, 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 £67M 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 To improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. Faculty of Infectious and Tropical Diseases The Faculty 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 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; macrophage-pathogen 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; intracellular trafficking and secretory pathways of cells of the immune system; 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; 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 immunoepidemiology; 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; 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; using anti-malarial antibodies as a marker of malaria exposure & assessment of the use of sero-epidemiology to monitor and target malaria control measures; 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; characterisation of protective immune mechanisms and defined antigens in attenuated vaccine models of schistosomiasis; 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; the identification and evaluation of novel drugs and drug delivery systems for leishmaniasis, trypanosomiasis and malaria, interaction between antiprotozoal drugs and the immune response. 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, purposebuilt 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 An effective malaria vaccine is needed, particularly against P. falciparum as this species causes more human mortality than all other eukaryotic pathogens combined. An understanding of natural selection operating on parasites in local endemic populations can enable understanding of molecular mechanisms of parasite invasion and immune evasion. Powerful methods are now being developed for population genomic analyses and selection experiments on parasites in culture, and these will be used together to identify optimal candidate components for a vaccine. The research programme funded by an ERC Advanced Award to Prof David Conway will take an integrated approach to understanding pathogen adaptation, by designing experiments based on analysis at the molecular, functional, and population levels. (i) Population genetic analyses of P. falciparum in sites of contrasting endemicity in West Africa, to finely determine signatures of selection with high-resolution throughout the genome, and understand the importance of differences in local population structure. Some of the results will help refine hypotheses on mechanisms used by merozoites to invade erythrocytes and evade acquired immune responses. (ii) Experimental culture analysis of merozoite invasion into erythrocytes to identify the receptor-ligand interactions used by different parasite populations. Novel receptor knockdown assays on cultured erythrocytes will be employed, and parasite adaptation experiments to identify constraints on the use of alternative invasion pathways. (iii) Innovative approaches to select individual parasites and characterise cell tropism, transcript profiles, and genome sequences. Such single-cell analysis is aimed to revolutionise approaches to genetics and phenotyping of parasites in the future. Candidate molecule discoveries will be taken forwards to receptor-ligand interaction assays, antibody inhibition and immuno-epidemiological studies. The Research Fellow in Population Genomics will focus on point (i) of the above, and on the genomic components of point (iii). JOB DESCRIPTION Post: Research Fellow Grade: AP6 Responsible to: Professor David Conway Department: Pathogen Molecular Biology Main duties and responsibilities: To be responsible for leading major aspects of the statistical analysis of population genetic structure and signatures of natural selection on malaria parasites To be critically involved in development and evaluation of hypotheses on mechanisms of natural selection and non-equilibrium population structure in malaria parasites To take a key role in co-ordinating ongoing preparation of parasite genomic material from new clinical samples for sequencing To complete and write up excellent research output for timely publication To develop and help manage the computational capacity and facilities for Bioinformatics within the research group, and contribute to strategic growth in genomics research collaboration with other investigators and groups at LSHTM 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 LSHTM and collaborators in endemic countries, working with other members of LSHTM and the Wellcome Trust Sanger Institute to help develop the research field generally 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). PERSON SPECIFICATION Essential: a) PhD in genetical or statistical sciences b) Evidence of high quality and consistent research productivity including excellent publications c) Solid successful experience in analysis of complex data sets including genomic-scale or population genetic data d) Ability to work very effectively in interaction with others of different backgrounds within a research team and in collaboration across institutes Desirable: e) Strong and demonstrably productive experience working with laboratory, clinical or field scientists in study design and data analysis f) Experience in infectious disease research g) Experience or interest in epidemiology h) Considerable experience in computer programming i) Strong ability in scientific communication including writing and personal presentation SALARY AND CONDITIONS OF APPOINTMENT The post is funded by the European Research Council (ERC) until 30th June 2017 and is available from 1st October 2012. Salary is on the Academic Pathway Salary scale from £35,661 to £40,499 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". APPLICATIONS Applications should be made on-line via our website at http://jobs.lshtm.ac.uk The reference for this post is DC-ERC1. 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. Closing date for the receipt of applications is 21 September 2012. 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