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Transcript
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 [email protected]. 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 [email protected]. 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