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Transcript
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE
(University of London)
FACULTY OF INFECTIOUS AND TROPICAL DISEASES
DEPARTMENT OF PATHOGEN MOLECULAR BIOLOGY
Research Fellow
In the areas of Molecular and Cell Biology
We are seeking to appoint a Research Fellow to be based at our partner laboratory
at the Harvard School of Public Health, Boston, USA
We are hoping to appoint an individual with an interest in the biology of malaria
parasites to work on protein kinases that play key roles in a number of life cycle
stages. This project will involve the use of state-of-the-art conditional knockdown
approaches in Plasmodium falciparum. The aim will be to investigate the interaction
of the cGMP and calcium signalling in regulating key phases of the parasite life cycle.
The successful applicant will have extensive experience with molecular biology, cell
culture and functional analysis. Previous experience with P. falciparum is an
advantage.
The post is funded by the Wellcome Trust for an initial period of 12 months, with the
possibility of extension by our partner laboratory, and is available immediately. The
salary is on the Overseas Research Fellow scale £32,025 per annum inclusive plus
allowances if applicable.
Applications should be made on-line via our website at http://jobs.lshtm.ac.uk. The
reference is this post is DB04. Any queries regarding the application process may be
addressed to [email protected]. A CV and names of two referees, who may be
approached immediately, if shortlisted should also be included with the on-line
application..
“The London School of Hygiene & Tropical Medicine is committed to being an
equal opportunities employer”
GENERAL INFORMATION
The London School of Hygiene & Tropical Medicine
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 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, 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
The School's mission is to improve health in the UK and worldwide through
excellence in public and global health research, teaching and knowledge translation,
working in partnership.
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 (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.
Teaching Requirements
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).
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
Wellcome Trust funded project in UK and US on signal transduction in malaria
parasites
The Wellcome Trust has funded two postdoctoral fellowships to study the biological
function of the cGMP-dependent protein kinase from the malaria parasite
Plasmodium falciparum (PfPKG). One of the posts has been filled already and will be
based primarily in David Baker’s lab in the Department of Pathogen Molecular
Biology at the London School of Hygiene & Tropical Medicine. The second post is
now available and is for an initial period of 12 months (with the possibility of
extension by our partner lab) and will be based in Manoj Duraisingh’s lab at the
Harvard School of Public Health. It will be possible for the research fellows to make
reciprocal lab visits. The aspect of the work to be carried out in the Harvard lab will
make use of conditional mutant parasites to investigate the interaction of the calcium
and cGMP signalling pathways in Plasmodium falciparum asexual and sexual blood
stage development.
PKG has been shown to play key roles in several malaria parasite life cycle stages
including: gametogenesis, merozoite egress, ookinete motility and late liver stage
development. The molecular details of exactly how this protein kinase mediates
these events are largely unknown. Much of what we do know has relied on the use of
highly specific inhibitors in conjunction with an inhibitor-resistant transgenic line
generated by allelic replacement. This study aims to further capitalize on these and
other tools in the partner labs to elucidate the cellular processes and downstream
molecules regulated by cGMP signalling.
JOB DESCRIPTION
Post:
Research Fellow
Grade:
Academic pathway Grade 6
Responsible to:
David Baker/Manoj Duraisingh
Department:
Pathogen Molecular Biology
Main duties and responsibilities:

In partnership with the Harvard investigator and the London-based lead
investigator, carry out research in molecular and cell biology according to the
project described above. The post holder will primarily be based in the
Duraisingh lab at Harvard. The work will require construction of plasmid
vectors and generation of transgenic Plasmodium falciparum lines and
analysis of their phenotypes. This will involve extensive parasite culture
(asexual and sexual stages), and use of cell-based and biochemical assays.

Collate and analyse research data and prepare it for presentation and
publication;

Keep meticulous records of experimental details and analysis of results.

Co-author publications;

Contribute to day-to-day running of the research laboratory and grant related
issues as directed;

Attend and contribute to weekly laboratory meetings, journal clubs,
department seminars, conferences and other academic gatherings;

Contribute to the Faculty teaching programme.
PERSON SPECIFICATION
Essential:

First degree and PhD in a relevant area of biological sciences

In depth experience of working with Plasmodium falciparum

In depth experience with constructing plasmid vectors

In depth experience with E. coli protein expression

Proven meticulous approach to experimental work, recording and analysis of
results and work organisation

Ability to work to deadlines and a flexible approach to working hours
Desirable:
Hands-on experience with:

transfection of Plasmodium falciparum

protein kinase assays, protein fractionation

immunoprecipitation/pull-down of proteins
5.
SALARY AND CONDITIONS OF APPOINTMENT
The post is funded by the Wellcome Trust for an initial period of 12 months (with the
possibility of extension by our partner laboratory) and is available immediately. The
salary is on the Research Fellow scale £32,025 per annum inclusive plus allowances
if applicable. Annual leave entitlement is 30 working days per year for all staff (prorata 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 jobs.lshtm.ac.uk. The
reference for this post is DB04.
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