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LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE
(University of London)
DEPARTMENT OF INFECTIOUS AND TROPICAL DISEASES
IMMUNOLOGY UNIT
SCIENTIFIC OFFICER – SC03
FURTHER PARTICULARS
1.
ADVERTISEMENT
SCIENTIFIC OFFICER
We are seeking to appoint a Scientific Officer to work on two anti-leishmanial drug
discovery projects.
The successful candidate will hold a degree in biology, biological sciences or
microbiology. They will have a keen interest in the identification of new drugs for the
treatment of parasitic diseases as well as proven experience in molecular biology
techniques. She or he will be organised, able to adopt a precise & systematic
approach to work with excellent data recording and basic computer literacy skills.
The ability to communicate and work well within a laboratory community is essential.
The post is full time funded by the European Commission & The University of
Mississippi for a period of 26 months. Salary is on the Professional Support
Pathway Grade 4 from £26,352 to £29,996. The successful candidate will be placed
on the scale according to skills and experience.
Informal enquiries can be made by email to Prof. Simon Croft
([email protected]) or Dr Vanessa Yardley ([email protected]).
Applications should be made on-line via our website at jobs.lshtm.ac.uk. The closing
date is Monday 14 June 2010 and the reference for this post is SC03. Applications
should also include a CV and the names and email contacts of 2 referees who can
be contacted immediately if shortlisted. 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 telephone 0207 927
2173.
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.
Project information
LEISHDRUG: Targeting the Leishmania kinome for the development of novel
anti-parasitic strategies. Visceral leishmaniasis is caused by the protozoan
parasites Leishmania donovani and Leishmania infantum and is a potentially fatal
disease in endemic areas around the world. During the infectious cycle, Leishmania
alternate between the insect promastigote stage and the vertebrate aflagellate
amastigote stage that proliferates inside infected host macrophages provoking the
pathology of the disease. This consortium uses a highly interdisciplinary approach to
reveal Leishmania signaling molecules associated with amastigote virulence, with the
major aim to exploit parasite-specific pathways for anti-leishmanial drug
development. We use innovative drug screening concepts not applied previously on
parasitic systems. We will utilize visual high-content screening to discover
compounds capable to kill intracellular Leishmania amastigotes without deteriorating
the host cell. This phenotype-based strategy relies on fluorescent parasites and
macrophages as read-outs and will allow simultaneous assessment of antileishmanial activity and host cell toxicity under physiological conditions. We will apply
a target-based strategy utilizing recombinant Leishmania protein kinases for inhibitor
identification and structure-guided drug design. The identification of appropriate
target kinases, with only limited homology to their mammalian counterparts will rely
on (i) in silico analysis by applying novel bioinformatic tools developed by consortium
members, and (ii) in vitro assay based on their phospho-transferase activity towards
recombinant Leishmania phospho-proteins. The major objectives of this proposal are
(i) to screen small molecule and peptide libraries for hit compounds with
leishmanicidal activity using phenotype- and target-based strategies, (ii) to identify
anti-parasitic lead compounds and assess their pharmacokinetic profiles using cellculture and experimental infection models for leishmaniasis, and (iii) to initiate lead
optimization by structure-based drug design.
As a partner in the LEISHDRUG consortium, LSHTM will be involved in the
evaluation and validation of novel anti-leishmanial compounds in macrophage and
mouse models of infection, part of the hit-to-lead cluster. This Project is funded by
the European Commission (FP7).
Natural product leads for new drug discovery against Leishmaniasis.
Natural products provide a rich source of novel prototypes– particularly as previously
unexplored biosphere niches are investigated, new molecular targets are discovered,
more sensitive and robust assay methods are developed, and technological
advances in dereplication, isolation, and structure elucidation are achieved (Clardy
and Walsh, 2004). The biological diversity displayed in the natural world reflects an
even richer underlying chemical diversity – and a vast source of novel structures with
biological activities such as chemical defence or other functions (Koehn and Carter,
2005). Secondary products, isolated from natural sources, predominantly
microorganisms and plants, have provided us with many of the therapeutic agents
currently on the market (Butler, 2008). Past and current natural product antileishmanial drug discovery efforts have mostly evaluated the extracts and natural
products derived from plants. Large number of plant extracts and the purified natural
products have been identified with promising anti-leishmanial activity in vitro. A few
them have also been evaluated in vivo mostly in VL models. However none of them
have advanced to clinical level. No significant efforts have been made regarding
evaluation of marine and microbial natural products for anti-leishmanial drug
discovery.
In vivo efficacy evaluation against viscerotropic species of Leishmania (LSHTM); the
compounds will be initially tested at single dose, which will be decided on the basis of
maximum tolerated dose assay carried with a limited number (2- 3) of healthy,
normal mice. The compounds showing >80% inhibition of the amastigote load in liver
and spleen will be screened for dose response evaluation. Mice (BALB/c) will be
infected with 1-2 x 107 L. donovani (MHOM/ET/67/HU3) amastigotes intravenously.
The test compounds will be administered 7 days post infection. Mice will be dosed
daily subcutaneously for 5 days once/day, and the other compounds (NPC1 161B
and sitamaquine) will be given orally. The compounds will be prepared in an
appropriate vehicle to achieve a good solubility or uniform suspension. Mice will be
sacrificed 14 days post-infection. Liver impression smears will be made, and parasite
burdens will be counted and compared to the untreated control group. Fifty percent
effective doses (ED50) will be calculated by linear regression analysis (Prism™).
Confidence limits for ED50 and ED90 values will be derived using MS Excel and
Prism.
3.
JOB DESCRIPTION
Post:
Scientific Officer
Grade:
Professional Support Pathway Grade 4
Responsible to:
Prof. Simon Croft and Dr Vanessa Yardley
Prof. Eleanor Riley (Head of Immunology Unit)
Unit:
Immunology Unit
Start date:
ASAP
Main duties and responsibilities:

Maintain Leishmania spp. parasites in in vitro culture and in in vivo models of
infection, under Cat 2 and Cat 3 Codes of Practice.

Record activity of compounds against Leishmania spp.

Keep meticulous records on compound arrival in database, record
experimental details and analysis of results.

Assist with the development of new methodologies for drug evaluation.

Assist in the day-to-day running of the laboratory.

Monitoring essential laboratory equipment and reagents to ensure smooth
day-to-day running of the project, including ordering reagents and materials.

Attend necessary courses and training in aseptic techniques, computer skills
and handling of radioactive substance if necessary to enable full participation
in the project.

Attend regular lab meetings to discuss research progress and work planning
with Dr. Vanessa Yardley in order to meet deadlines required by the project.

Observe School and Departmental Safety Guidelines relating to good
laboratory practices and the handling of pathogenic materials.

Assist with teaching of students and visiting workers in the laboratory when
required.

Draft SOPs of new techniques developed during the course of the projects.
4.
PERSON SPECIFICATION
Qualifications, Skills and Knowledge:
Essential:

Degree in a relevant area of biological sciences.

Experience or willingness to work under Category 3 regulations.

Experience or willingness to learn relevant in vitro aseptic culture techniques,
preferably with particular reference to maintenance of Leishmania spp.
parasites in culture and in vivo experimental models of Leishmania.

Ability to record experimental details and analyse results

Ability to organise his/her own work.

Ability to work to deadlines.

Basic computer skills (Word, Excel, Prism)

A flexible approach to working hours

Experience in molecular biology techniques – specifically development of
quantitative PCR protocols, transfection techniques.
Desirable:

To be a holder of a Personal Home Office License

MSc in a related discipline

Interest in searching scientific literature relevant to the project, in particular
new techniques to evaluate drug activity.
Communication and interpersonal skills:

Ability to interact effectively with other members of the team and also with
colleagues in the shared culture facilities

Ability to develop and maintain excellent relationships with all categories of
staff and students to ensure productive work together.

Ability to work independently and as part of a team.

Willingness to assist in the training of students, visiting workers or new staff in
the laboratory.

Ability to interact with international partners in a highly professional manner.
5.
SALARY AND CONDITIONS OF APPOINTMENT
The post is funded by European Commission and the University of Mississippi for a
period of 26 months. Salary is on the Professional Support Pathway Grade 4 Salary
scale from £26,352 to £29,996, inclusive. The successful candidate will be placed on
the scales according to skills and experience.
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 SC03. Applications should also include a CV and 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 Monday 14 June
2010. Interviews are scheduled to be held week commencing 28 June 2010.
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