Download Department of Pathogen Molecular Biology

Department of
Pathogen Molecular
Biology
Academic Staff Profiles
Head of Department: David Conway
Department Research Degree Co-ordinator: Sam Alsford
Department Operating Officer: Evelyn Sawyer
Tel: +44 (0)20 7927 2639 Fax: +44 (0)20 7927 2739
Contents
Mission statements ................................................................................................ p3
Academic staff
Professor David Conway (Head of Department) ...................................................... p5
Professor Brendan Wren (Head of Faculty) ............................................................. p6
Professor David Baker ............................................................................................ p7
Professor Mike Blackman......................................................................................... p8
Professor Taane Clark ............................................................................................. p9
Professor Martin Hibberd ....................................................................................... p10
Professor John Kelly .............................................................................................. p11
Professor Michael Miles ......................................................................................... p12
Professor Polly Roy ................................................................................................ p13
Professor Nick Thomson ........................................................................................ p14
Dr Graham Clark .................................................................................................... p15
Dr Ursula Gompels ................................................................................................. p16
Dr Cally Roper ........................................................................................................ p17
Dr Sam Alsford ....................................................................................................... p18
Dr Stephen Baker ................................................................................................... p19
Dr Susana Campino ……………………………………………………………………. p20
Dr Johannes Dessens ............................................................................................ p21
Dr Nick Dorrell ........................................................................................................ p22
Dr Richard Stabler .................................................................................................. p23
Dr Martin Taylor ..................................................................................................... p24
Dr Teresa Cortes ………………………………………………………………………...p25
Dr Jon Cuccui ......................................................................................................... p26
Dr Lisa Dawson ...................................................................................................... p27
Dr Nick Furnham .................................................................................................... p28
Dr Michael Gaunt ................................................................................................... p29
Dr Esmeralda Valiente ........................................................................................... p30
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Mission statements
London School of Hygiene and Tropical Medicine
The mission of the LSHTM 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. Researchers have expertise in public
health medicine, epidemiology, clinical medicine, infectious diseases, chemotherapy,
biochemistry, immunology, genetics, molecular biology, entomology, statistics,
demography, health economics, public health engineering, medical anthropology,
health promotion, and health policy.
Faculty of Infectious and Tropical Diseases (ITD)
ITD encompasses laboratory-based research as well as clinical and interventional
studies of infectious and tropical diseases. The range of disciplines represented in the
Faculty is broad, and inter-disciplinary research is a feature of much of our work. 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, vector biology and disease control. The Faculty is
organized into four Departments comprising: Disease Control, Clinical Research,
Infections and Immunology and Pathogen Molecular Biology. There is close interaction
between scientists in different departments. The Faculty has strong overseas links,
which provide a basis for field studies and international collaborations in developed
and developing countries.
Department of Pathogen Molecular Biology (PMB)
Research in PMB focuses on the molecular biology and genetics of pathogens and
their hosts, in order to improve the understanding and control of infectious diseases.
Core areas of our research include: (i) determining mechanisms of infection used by
diverse eukaryotic, bacterial and viral pathogens, (ii) studying immune evasion
mechanisms of pathogens, (iii) understanding genetic diversity and evolution of
pathogens, (iv) exploiting particular pathogens as model biological systems, and (v)
developing practical applications including improved diagnostics, antimicrobials and
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vaccines. Research in the department focuses on causes of malaria (Plasmodium
species), Chagas disease (Trypanosoma cruzi), African sleeping sickness
(Trypanosoma brucei), amoebic dysentery (Entamoeba), the Leishmania species,
food borne pathogens (Campylobacter jejuni and Yersinia enterocolitica), causes of
gastric ulcers and cancer (Helicobacter pylori), pseudomembranous colitis
(Clostridium
difficile),
plague
(Yersinia
pestis),
melioidosis
(Burkholderia
pseudomallei), tuberculosis (Mycobacterium tuberculosis), bacterial pneumonia
(Streptococcus
pneumoniae),
bluetongue
virus,
herpesviridae,
and
enteric
rotaviruses.
Collaborations
We have outstanding collaborations with many scientists internationally, including
those in disease endemic countries. Many members of PMB spend time at overseas
research sites, and have major roles in research in Africa, South America and South
East Asia. We also frequently host academics and students on research visits to
London as an integral part of these collaborations.
PMB has also played a major role in establishing strategic partnerships between
LSHTM and other major UK research institutions. This includes a strong alliance with
the Wellcome Trust Sanger Institute, and we are planning for collaboration with
programmes being established at the Francis Crick Institute. A particularly important
new initiative is the formation of the Bloomsbury Research Institute (BRI), a substantial
venture between University College London and LSHTM. The BRI will bring together
key basic science and translational approaches from across both institutions to provide
an optimal environment to develop new drugs, vaccines and diagnostics.
More details on the PMB Department can be found on www.lshtm.ac.uk/itd/pmbd/
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H e a d o f D e pa rt m e n t
David Conway
Professor of Biology
David Conway has developed several successive research
programmes based in London and in Africa. One of his major
interests is mechanisms of selection operating on parasites in
natural populations and in laboratory culture, as understanding
these should help guide development of new interventions as well
as use of existing ones. For example, extracellular malaria parasite
merozoites in the blood use a range of different receptors to invade
erythrocytes. His research aims to understand how enough of them
survive and reproduce in the face of acquired immunity, and how future interventions
such as blood stage vaccines might have an impact. Use of population genetic
analyses, conducted at the whole genome scale, enables investigation to be
subsequently
focused
on
particular candidate genes and
their products. The relevance of
parasite proteins as targets of
acquired immunity in humans is
studied by correlation of immune
responses with risk of clinical
malaria. The focus is mostly on
Plasmodium
falciparum
in
African populations with diverse
endemicity and levels of
immunity.
This
enables
comparisons of results across populations in order to test and refine hypotheses, and
improve design of experiments to validate molecular targets and mechanisms. He also
works on molecular epidemiology of Plasmodium knowlesi in Southeast Asia, and has
previously conducted research on trachoma and intestinal nematode infections.
Selected publications
1. Admixture in humans of two divergent Plasmodium knowlesi populations associated with
different macaque host species. Divis PCS et al. PLOS Pathogens 2015.
2. Comparison of genomic signatures of selection on Plasmodium falciparum in different
regions of a highly endemic country. Duffy CW, et al. BMC Genomics 2015.
3. Population genomic structure and adaptation in the human malaria parasite Plasmodium
knowlesi. Assefa SA, et al. Proc Natl Acad Sci USA 2015.
4. Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West
African populations of differing infection endemicity. Mobegi VA, et al. Mol Biol Evol 2014.
5. Population genomic scan for candidate signatures of balancing selection to guide antigen
characterization in malaria parasites. Amambua-Ngwa A, et al. PLOS Genetics 2012.
www.lshtm.ac.uk/aboutus/people/conway.david
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H e a d o f F a c u l ty
Brendan Wren
Professor of Microbial Pathogenesis
Brendan Wren’s research interests include determining the
genetic basis by which bacterial pathogens cause disease.
Research on individual pathogens include; Clostridium difficile,
Campylobacter jejuni, Helicobacter pylori, Burkholderia
pseudomallei, Coxiella burnetti, Vibrio cholerae, Acitinobacillus
pleuropneumoniae,
Streptococcus
suis,
Streptococcus
pneumonia and the enteropathogenic Yersinia. The research
group exploits a range of post genome research strategies to
gain a comprehensive understanding of how these pathogens function, how they
evolve and how they interact with their respective hosts. Comparative phylogenomics
is used to study the phylohistory and phylogeography of the bacteria we study, which
provide clues to the evolution of bacterial virulence.
Another major research area is understanding the
role of glycosylation in bacterial pathogenesis. This
basic research has led to practical applications in
the cloning and expression of bacterial glycan
structures in E. coli with the development of Protein
Glycan Coupling Technology for the construction of
new and inexpensive glycoconjugate vaccines for
human and animal diseases.
Circular representation of the plague
bacterial genome
Selected publications
1. Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus
suis. Weinert LA, et al. Nature Comm 2015.
2. The post translational modification of the Clostridium difficile flagellin affects motility, cell
surface properties and virulence He M, et al. Molecular Microbiology 2014.
3. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. He M,
et al. Nature Genetics 2013.
4. Exploitation of bacterial N-linked glycosylation to develop a novel recombinant
glycoconjugate vaccine against Francisella tularensis. Cuccui J, et al. Open Biology 2013.
5. Bacterial pathogenomics. Pallen M & Wren B. Nature 2007.
www.lshtm.ac.uk/aboutus/people/wren.brendan
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David Baker
Professor of Malaria Parasite Biology
David Baker’s research is focused on determining the role
of cyclic nucleotide signalling in regulating progression of
the P. falciparum life cycle. Work from the Baker group has
shown essential roles for the cGMP-dependent protein
kinase (PKG) in gametocyte activation and ookinete
motility in the mosquito stages and in merozoite egress and
invasion in the blood stages. David Baker recently received
a Wellcome Trust Senior Investigator Award (jointly with
Professor Mike Blackman from the Francis Crick Institute)
to dissect the role of cGMP signalling in the P. falciparum blood stages. David’s group
is also investigating enzymatic components of the cyclic nucleotide signalling
pathways as novel antimalarial drug targets with recent grant from the Medical
Research Council and the GSK Open lab Foundation in Tres Cantos, Spain.
A chemical genetic approach to determine the role of PKG during
life cycle progression
Selected publications
1. Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating
egress and invasion. Alam, et al. Nat Commun 2015.
2. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for
Malaria Parasite Transmission Ramdani, et al. PLoS Pathog 2015.
3. Crystal Structures of the Carboxyl cGMP Binding Domain of the Plasmodium falciparum
cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress.
Kim et al. PloS Pathog 2015.
4. Phosphoinositide biosynthesis links cGMP-dependent protein kinase to essential Ca2+
signals at key decision points in the life cycle of malaria parasites. PLoS Biol 2014.
5. A transcriptional switch underlies commitment to sexual development in human malaria
parasites. Kafsack, et al. Nature 2014.
http://www.lshtm.ac.uk/aboutus/people/baker.david
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Mike Blackman
Professor of Molecular Parasitology



Mike Blackman’s research focuses on the biology of
Plasmodium falciparum, the agent of the most dangerous form
of malaria. His work aims to understand the molecular
mechanisms by which the parasite enters and exits its host
cell, and to dissect the structural changes that occur in the
host erythrocyte and at the parasite surface during invasion
and egress. A major aim is to translate this information into
health benefits by identifying drug-like inhibitors of enzymes
and other parasite molecules involved in egress and invasion.
Current research focuses on:
The proteolytic pathway that leads to egress, initiated
by a malarial serine protease called SUB1.
The kinase-mediated signalling events that trigger
egress.
Red blood cell invasion and the parasite enzymes and
ligands involved.
Selected publications
1. Processing of Plasmodium falciparum merozoite surface
X-ray crystal structure of SUB1, a
protein MSP1 activates a spectrin-binding function
protease essential for release of
enabling parasite egress from RBCs. Das S, et al. Cell Host
malaria parasites from red blood
cells
& Microbe 2015.
2. The malaria parasite egress protease SUB1 is a calciumdependent redox switch subtilisin. Withers-Martinez C, et al. Nature Communications 2014.
3. Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory
organelle discharge and egress. Collins CR, et al. PLoS Pathogens 2013.
4. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous
culture in human erythrocytes. Moon RW, et al. Proc Natl Acad Sci USA 2013.
5. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and
essential, & helps evade invasion-inhibitory antibodies. Olivieri A, et al. PLoS Pathogens 2013.
http://www.lshtm.ac.uk/aboutus/people/blackman.mike
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Taane G. Clark
Professor of Genomics and Global Health
Taane Clark’s research interests include using high throughput
genotyping and sequencing technologies to understand the
causes of infectious diseases. This work involves leading
global collaborations, developing methods to exploit ‘omic
technologies and data in research and clinical settings, and
building capacity in infectious disease ‘omics and
epidemiology.
Selected projects include:
 Using human GWAS approaches to
understanding genetic factors underlying
malaria susceptibility and immunology;
 Understanding malaria parasite diversity
through
whole
genome
sequencing,
population genetic analysis, and developing
molecular barcoding tools.
 Detection of novel mutations involved in M.
tuberculosis drug resistance and virulence
using whole genome sequencing, association and evolutionary analysis;
 Elucidating tuberculosis host-pathogen interactions using high throughput genomic
technologies.
Selected publications
1. Polymorphisms in USP38, FREM3, SDC1, DDC and LOC727982 genes and differential
susceptibility to severe malaria phenotypes in Tanzania. Manjurano A, et al. J Infectious Dis
2015.
2. African Glucose-6-phosphate dehydrogenase alleles associated with protection from severe
malaria in heterozygous females in Tanzania. Manjurano A, et al. PloS Genetics 2015.
3. Rapid determination of anti-TB drug resistance from whole-genome sequences. Coll, et al.
Genome Medicine 2015.
4. A barcode of organellar genome polymorphisms identifies the geographic origin of
Plasmodium falciparum strains. Preston MD, et al. Nature Commun 2014.
5. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Coll, et al.
Nature Comm 2014.
pathogenseq.lshtm.ac.uk
http://www.lshtm.ac.uk/aboutus/people/clark.taane
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Martin Hibberd
Professor of Emerging Infectious Diseases
Martin Hibberd’s career has progressed from microbiology to
human genetics and now concentrates on genomic sciences
for a variety of infections. Since the emerging infectious
disease SARS outbreak, it has become clear that genomic
and holistic approaches to infectious diseases can give rapid
tools for public health impact. These approaches can give
novel and sometimes unexpected insights into the disease.
These may be turned into diagnostics, prognostics and therapeutic targets. Utilizing
human population diversity to understand host-pathogen interactions has revealed
specific disease control mechanisms. Looking at the host response to infection on a
global scale can identify the rapid temporal changes and the critical points in the
disease. Whole genome pathogen investigations complete the molecular picture and
inform on the transmission process. Genomic hypotheses require molecular
confirmation; for example, macrophage cells respond to TB infection with distinct TLR
proteins.
Combining
these
approaches can lead to strong
insights and accurate models of
the disease process that can be
used
to
identify
novel
intervention strategies. Using
both pathogen and host diversity
is also key to understanding the
A microarray expression profile of dengue patients identifies novel
dynamic process of molecular
processes that occur before disease onset.
interaction, that is now known to
be modified by other infectious agents, or through an interaction with commensal
communities.
Selected publications
1. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling
provides insights into anti-tuberculosis drug resistance. Phelan J, et al. BMC Med 2016.
2. Genomic approaches for understanding dengue: insights from the virus, vector, and host.
Sim S, Hibberd ML. Genome Biol 2016.
3. Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who
Regularly Consumes Camel Meat and Milk. Lee GH, et al. Gastroenterology 2016.
4. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from
Vietnamese children identifies distinct patterns of inter- and intra-host evolution. Do LA, et al.
J Gen Virol 2015.
5. Variation at HLA-DRB1 is associated with resistance to enteric fever. Dunstan SJ, et al. Nat
Genet 2014.
www.lshtm.ac.uk/aboutus/people/hibberd.martin
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John Kelly
Professor of Molecular Biology
John Kelly’s main research interests focus on the parasitic
protozoan Trypanosoma cruzi, which is responsible for Chagas
disease. This infection represents a major public health problem
in Latin America, and is increasingly being detected in nonendemic regions because of migration. Advances by ourselves,
and others have led to the generation of a wide range of genetic
tools that can be used to address
fundamental
biological
questions
associated with these important
pathogens. In addition, highly sensitive
imaging technology that we have developed is providing a
research framework where rapid progress can be expected.
We are exploiting these new approaches and opportunities to
T. cruzi replicating amastigote
gain greater understanding of the mechanisms of drug action forms (red dots) inside infected
and resistance, and disease pathogenesis. In collaboration mammalian cells.
with biologists, biochemists and organic chemists, we have validated a number of
parasite drug targets and identified several lead
compounds that show promise in terms of therapeutic
development. This multidisciplinary approach, which brings
together both academic and industrial partners, is widely
seen as the way ahead to provide better treatments for this
previously ‘Neglected Diseases’.
T. cruzi insect stage
epimastigote form.
Selected publications
1. Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics
and chronic cardiomyopathy. Lewis M, et al. Cellular Microbiology 2016.
2. The limited ability of posaconazole to cure both acute and chronic Trypanosoma cruzi
infections revealed by highly sensitive in vivo imaging. Fortes Francisco A., et al. Antimicrob
Agents Chemother 2015.
3. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific
parasite dynamics and heart disease in the absence of locally persistent infection. Lewis M.
et al.Cellular Microbiology 2014.
4. Evidence that transport of iron from the lysosome to the cytosol in African trypanosomes
is mediated by a mucolipin orthologue. Taylor M, et al. Molecular Microbiology 2013.
5. Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise
independently in a single population. Mejia A, et al. J. Infectious Diseases 2012.
www.lshtm.ac.uk/aboutus/people/kelly.john
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Michael Miles
Professor of Medical Protozoology
Michael Miles’s research is primarily focused on Trypanosoma
cruzi, the agent of Chagas disease (South American
trypanosomiasis) and on Leishmania species, the agents of
visceral (VL) and mucocutaneous leishmaniasis (MCL),
encompassing fundamental laboratory research and fieldwork in
endemic areas. Principal research interests are the presence,
importance and mechanisms of genetic exchange in
experimental and natural populations of these organisms, and
the molecular epidemiology of Chagas disease and the leishmaniases in the context
of improvement of control strategies. Other interests are comparative genomics,
diagnostics development, the ecology and population genetics of triatomine bugs, the
ecology and behaviour of South American mammals, and the control of African
trypanosomiasis. Recent achievements of the research group include the first
experimental proof of genetic exchange in T. cruzi; demonstration that sylvatic
Rhodnius prolixus does invade houses in Venezuela, and several detailed population
genetics studies of natural populations of T. cruzi using multilocus sequence typing
(MLST) and microsatellite analysis (MLMT). Coordinator, of the European/Latin
American FP6 network (LeishEpiNetSA), 12 partners, to 2010 - Coordinator (assisted
by Martin Llewellyn), of the European/Latin American FP7 network (ChagasEpiNet),
15 partners, to 2012.
Selected publications
1. Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure,
hybridization and a role for humans in Andean parasite dispersal. Messenger LA, et al. Mol
Ecol. 2015.
2. Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and
diversifying selection among chronic and congenital Chagas disease patients. Llewellyn MS,
et al. PLoS Negl Trop Dis 2015.
3. Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T.
cruzi VI CL Brener. Franzen O, et al. PLoS Negl Trop Dis 2011.
4. Recent, independent and anthropogenic origins of Trypanosoma cruzi hybrids. Lewis MD, et
al. PLoS Negl Trop Dis 2011.
5. Analysis of molecular diversity of the Trypanosoma cruzi trypomastigote small surface
antigen reveals novel epitopes, evidence of positive selection and potential implications for
lineage-specific serology. Bhattacharyya T, et al. Int J Parasitol 2010.
www.lshtm.ac.uk/aboutus/people/miles.michael
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Polly Roy
Professor of Virology
Polly Roy’s salient contribution has been the first completed
molecular understanding of the Orbiviruses, of the Reoviridae
family, a distinct group of several hundred viruses of serious
health and economic impact.
Roy used multi-disciplinary
approaches to provide a detailed understanding of the Bluetongue
virus (BTV), a major Orbiviruses pathogen and model for a range
of human and animal viruses with similar structure, including
human rotavirus. She has used virology, molecular biology,
immunology and structural biology studies as required, examining
each aspect of the virus, from individual virus proteins to virus
entry, assembly of the complete virus particle and its engagement,
at various levels, with the host cell. She has developed improved diagnostic assays,
more efficacious vaccines and alternate therapeutic possibilities in the addition to the
fundamental scientific advance discovered. Roy’s findings that co-expression of virus
structural proteins leads to the assembly of virus-like particles spawned an area of
expression technology that has seen the development of many candidate animal and
human vaccines. Roy’s team pioneered the first reverse system for BTV (the
synthesis of infectious virus solely from synthetic genes), a major achievement for this
class of viruses, which has allowed major studies of the
genetic basis for pathogenesis and the generation of
new efficacious vaccines for orbiviruses. Other ground
breaking advances has been the establishment of an
outstanding cell-free system to reconstitute infectious
BTV particles, a striking example of the use of synthetic
biology to generate viruses de novo. Recently using a
novel RNA-RNA interaction assay together with cellfree packaging assay, Roy’s team unravel how multisegmented viruses select and package their genome.
Roy’s contribution to virology, in particular to virus
structure and assembly, has been recognised by her
peers worldwide through numerous awards and prizes.
Selected publications
1.
2.
3.
4.
5.
Entry of Bluetongue virus capsid requires specific cellular lipid. Patel, et al. Journal of
Biological Chemistry 2016.
Atomic structure of a non-enveloped virus reveals pH sensors for a coordinated process
of cell entry. Zhang X, et al. Nature Structural and Molecular Biology 2016.
Disruption of Specific RNA-RNA interactions in a double-stranded RNA virus inhibits
genome packaging and virus Infectivity. Fajardo, et al. PLoS Pathogen 2015.
Rotavirus NRNAS are released by transcript-specific channels in the double-layered viral
capsid. Periz, et al. Proc Natl Acad Sci USA 2013.
In vitro reconstitution of Bluetongue virus infectious cores. Lourenco. Proc Natl Acad Sci
USA 2011.
http://www.lshtm.ac.uk/aboutus/people/roy.polly
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Nick Thomson
Professor of Bacterial Genomics and Evolution
Nick Thomson holds a split academic position between the
LSHTM and The Wellcome Trust Sanger Institute. During his
career he has transitioned from a classically trained Molecular
Biologist to a Genome Scientist using high throughput
sequencing technologies. His current work involves the
application of phylogeny to understand the contemporary or
historical distribution of bacterial
pathogens
causing
diarrheal
disease, including Shigella sonnei, Vibrio cholerae and
Salmonella. His work on cholera used modern techniques
and genomic data to identify a global source for pandemic
cholera. In addition his group has contributed to a ‘One
Health’ look at the flow of antimicrobial resistance (AMR)
and the zoonotic pathogen Salmonella Typhimurium
DT104 by considering isolates from both humans and farm
animals (Fig 1 & 2). He considers studies of this nature and
resolution to be essential if we are to identify the sources Figure 1. The phylogenetic
relationships of DT104 strains
and sinks of both food borne
found in animals and humans in
pathogens such as DT104 and AMR.
being
one of
ScotlandAMR
over a 22
year period.
the most important threats to public health. His groups
work on Chlamydia showed that despite the pervasive
notion that Chlamydia do not recombine, their genomes
showed evidence of widespread DNA exchange
between isolates affecting different body sites,
challenging much of our understanding of C. trachomatis
Figure 2. The number of transitions
evolution and epidemiology. To facilitate this, his group
between animals and humans
has developed methods to sequence Chlamydia directly
within the phylogeny.
from uncultured discarded clinical swabs, a methodology
with broad applications in clinical microbiology.
Selected publications
1. Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic
composed of multiple distinctive lineages. Andersson, et al. Nat Commun 2016.
2. Global phylogeography and evolutionary history of Shigella dysenteriae type 1. Njamkepo, et
al. Nature Microbiology 2016.
3. Species-wide whole genome sequencing reveals historical global spread and recent local
persistence in Shigella flexneri. Connor, et al. eLife 2016.
4. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance
in Klebsiella pneumoniae, an urgent threat to public health. Holt, et al. PNAS 2015.
5. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual
transmission: a cross-sectional study. Baker, et al. Lancet ID 2015.
www.lshtm.ac.uk/aboutus/people/thomson.nick
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Taught Course Director
Graham Clark
Reader in Molecular Parasitology
Graham Clark’s research interests include the genetic diversity
and evolution of gut protozoan parasites. The main organisms
studied are Entamoeba, which includes E. histolytica, the agent
of amoebic dysentery and amoebic liver abscesses, and
Blastocystis, an organism of
uncertain pathogenicity.
Current Research focuses on:
Entamoeba
 genome re-sequencing as a way to build on
earlier results indicating a parasite genetic
component linked to the outcome of
Entamoeba histolytica
infection.
 people who develop disease are infected with a different range of genotypes
from those who remain asymptomatic.
Blastocystis

investigating whether any of the genetic
subtypes of the organism are linked to the
symptoms found in some individuals.

sequencing its mitochondrial and nuclear
genomes in an attempt to understand the function
of the mitochondrion in this strictly anaerobic
organism.
Blastocystis sp.
Selected publications
1. Expanding the Entamoeba universe: new hosts yield novel ribosomal lineages. Jacob AS, et
al J Euk Microbiol 2016.
2. Recent developments in Blastocystis research. Clark CG, et al. Adv Parasitol 2013.
3. Genetic diversity of Blastocystis in livestock and zoo animals. Alfellani MA, et al. Protist 2013.
4. Genomic diversity of the human intestinal parasite Entamoeba histolytica. Weedall GD, et al.
Genome Biol 2012.
5. Levels of genetic diversity vary dramatically between Blastocystis subtypes. Stensvold CR,
et al. Infect Genet Evol 2012.
www.lshtm.ac.uk/aboutus/people/clark.graham
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Ursula Gompels
Reader in Molecular Virology
Ursula Gompels’ research is on human herpesviruses, recently on the betaherpesvirus
subgroup, human herpesvirus 6 (variants HHV-6A and HHV-6B) and human
cytomegalovirus (HCMV). These viruses can be significant paediatric pathogens and
are major opportunistic infections in immunosuppressed populations, as HIV/AIDS
and transplantation patients, causing morbidity and mortality. HHV-6A/B, are
emerging pathogens causing fatal encephalitis in immunosuppressed hematopoietic
transplant patients and linked to status epilepticus and myocarditis. Betaherpesviruses
cause lifelong latent infections adapted to persist in cells of our immune system, and
can reactivate to cause disease. Uniquely amongst
human herpesvirus, HHV-6A/B integrate in the germline
of approximately 1% humans, within the subtelomere of
our chromosomes, giving an inherited ‘congenital’
infection. Pathogenic effects are being studied including
infant development delays and cardiac disease. The
virus encode key immunological adaptations to the host
providing a toolbox to devise novel immune-based
Human herpesvirus chemokine,
medicines. Work is multidisciplinary covering infection ‘virokine’ arrests HIV CCR5 receptor
and immune modulation with implications for vaccine (green) at the cell surface.
studies and paediatric HIV/AIDS: i) effects of
betaherpesvirus on infant development in maternally HIV exposed infants, in
collaboration with EPH and the University Teaching Hospital in Zambia, ii) molecular
mechanisms of virus entry and iii) virus mimics of inflammatory mediators, chemokine
and chemokine receptors, these also inhibit HIV infection, and have major applications
to immunotherapeutics and vaccines.
Selected publications
1.
2.
3.
4.
5.
Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding
Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative
Mothers in Sub-Saharan Africa. Musonda K, et al. J Pediatric Infect Dis Soc 2016.
Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus
6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential
to Reactivate as an Emerging Infection. Tweedy, et al. Viruses 2016.
Analyses of germline, chromosomally integrated human herpesvirus 6A and B genomes
indicate emergent infection and new inflammatory mediators. Tweedy, et al. J Gen Virol
2015.
Activation of CCR2+ human proinflammatory monocytes by human herpesvirus-6B
chemokine N-terminal peptide. Clark, et al. J Gen Virol 2013.
Reduced Poliovirus vaccine neutralising-antibody titres in infants with maternal HIVexposure. Vaccine 2013.
www.lshtm.ac.uk/aboutus/people/gompels.ursula
P a g e 16 | 30
Cally Roper
Reader in Malaria Genetics
Cally Roper arrived to LSHTM with
a background in Evolution and
Population Genetics research. Her
interest is in the development and
application
of
novel
genetic approaches to questions
about malaria treatment and
malaria control. In particular, she is
interested
in resistance
to
antimalarial drugs and identifying
the factors which drive its
emergence and geographic dispersal.
Current projects include the development of a genetic
barcode, mapping resistance mutations in Africa to
inform policy on malaria prevention in pregnant women
and infants, measuring drug selection applied by the
adoption of specific treatment interventions in the
field, and assessing the role of human migration in the
dispersal of drug resistant malaria.
Malaria parasite molecular
epidemiology in Sri Lanka
Selected Publications
1. Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine
Resistance in P. vivax. Mette L, et al. PLOS Neglected Tropical Diseases 2015.
2. The influence of malarial transmission intensity and the 581G resistance mutation on the
protective effect of intermittent preventive treatment of malaria in pregnancy (IPTp): A
systematic review and meta-analysis Chico R, et al. Tropical Medicine and International Health
2015.
3. Barcoding Malaria Parasites: A barcode of organellar genome polymorphisms identifies the
geographic origin of Plasmodium falciparum strains. Preston MD, et al. Nature
Communications 2014.
4. Measuring drug pressure in a field trial of intermittent preventive treatment of infants (IPTi).
A community-randomised evaluation of the effect of IPTi on antimalarial drug resistance in
southern Tanzania. Pearce , R J, et al. The Journal of Infectious Diseases 2013.
5. Multiple origins and regional dispersal of resistant dhps in African P. falciparum malaria.
Pearce R, et al. PLoS Medicine 2009.
http://www.lshtm.ac.uk/aboutus/people/roper.cally
P a g e 17 | 30
Sam Alsford
Senior Lecturer in Molecular Parasitology
Sam Alsford’s early work focused on the development of a
range of molecular tools for use in the genetic manipulation of
Trypanosoma brucei, the causative agent of human African
trypanosomiasis (see http://blogs.lshtm.ac.uk/alsfordlab/celllines-plasmids/). This enabled the transition from candidatebased or reverse genetic approaches, to the use of forward
genetics in developing our understanding of trypanosome
biology.
Initially, this technology was applied to understanding
the uptake and intracellular transit of the current antiHAT drugs, in particular suramin, and identifying
potential routes to resistance2,4. It’s now being used to
define parasite’s interaction with other factors, including
novel anti-trypanosomatid drugs, nutrients and innate
immune factors3.
DNA
ELP3a ELP3b
Fig. 2: The nucleolar localization of the rRNA
transcriptional regulator, ELP3b.
DNA
ISG75
Fig. 1: Distribution of ISG75, a
surface protein responsible for
suramin uptake.
Sam Alsford is also interested in the control of
RNA polymerase I-mediated transcription of
rDNA and VSG in T. brucei. This work led to the
recent identification of a key regulator of
monoallelic VSG expression1, and the
identification of a novel role for the Elongator
protein, ELP3b, in the differential regulation of
rDNA array transcription5.
Selected publications
1. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes. Glover,
et al. Proc Natl Acad Sci 2016.
2. Modulation of the surface proteome through multiple ubiquitylation pathways in African
trypanosomes. Zoltner M, et al. PLoS Pathogens 2015.
3. Cathepsin-L can resist lysis by human serum in Trypanosoma brucei brucei. Alsford S, et al.
PLoS Pathogens 2014.
4. High-throughput decoding of anti-trypanosomal drug efficacy and resistance. Alsford S, et al.
Nature 2012.
5. Elongator protein 3b negatively regulates ribosomal DNA transcription in African
trypanosomes. Alsford S & Horn D, Mol Cell Biol 2011.
blogs.lshtm.ac.uk/alsfordlab
www.lshtm.ac.uk/aboutus/people/alsford.sam
P a g e 18 | 30
Stephen Baker
Senior Lecturer in Emerging Infections
Stephen Baker heads the enteric infections research group at
the Wellcome Trust Major overseas programme (WT-MOP) in
Ho Chi Minh City, Vietnam. His group studies the
microbiology, genetics, epidemiology and treatment of enteric
infections caused by members of the Enterobacteriaceae.
The Gram-negative Enterobacteriaceae incorporate a
number of enteric pathogens, including pathogenic variants of
E. coli (the most common cause of community-acquired
diarrhoea), Shigella spp., the cause of shigellosis, and the many serovars of
Salmonella enterica, including S. Typhi and S. Paratyphi A, the causative agents of
enteric (typhoid) fever. Transmission of the organisms frequently occurs via faecal
contamination of food, water and the environment. Thus, the risk of infection with
pathogenic members of the Enterobacteriaceae is higher in areas with poor sanitation
and hygiene. This is a significant global problem, as acute infectious diarrhoea is the
second biggest killer of children, accounting for 21% (~2.5 million annually) of
childhood deaths worldwide and S. Typhi and S. Paratyphi A are estimated to cause
>25,000,000 new infections annually with >200,000 deaths. Our current focus
combines microbiological, immunological and geographical information to study how
organisms are transmitted in urban environments and how this interplay can be used
to design and implement vaccination strategies. Areas of particular interest include: i)
Evolutionary adaptation and clonal replacement of gastrointestinal pathogens, ii)
Molecular diagnostics of bacterial pathogens, iii) The impact of antimicrobial
resistance, iv) Horizontal gene transfer. v) Epidemiological and clinical aspects of
gastrointestinal infections. vi) Randomised controlled trials for enteric infections, vii)
Serological markers of infection and pathogen exposure, viii) Genome sequencing and
pathogen genotyping.
Selected publications
1. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with
fluoroquinolone treatment failure. Pham Thanh D, et al. ELife 2016.
2. The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi modify host
responses and cellular interactions. Schreiber F, et al. Sci Rep 2015.
3. Epidemiology and Rising Prevalence of Pediatric Symptomatic and Asymptomatic Norovirus
Infections in Ho Chi Minh City, Vietnam. My PVT, et al. Emerg Infect Dis 2013.
4. Immune profiling with a Salmonella Typhi antigenmicroarray identifies new diagnostic
biomarkers of human typhoid. Liang L, et al. Nature Sci Rep 2013.
5. Shigella sonnei genome sequencing and phylogeneticanalysis indicate recent global
dissemination from Europe. Holt KE, et al. Nat Genet 2012.
www.lshtm.ac.uk/aboutus/people/baker.stephen
P a g e 19 | 30
Susana Campino
Senior Lecturer in Genomics
Susana Campino’s main field is the genomic epidemiology
of malaria, applied to the human host and Plasmodium
parasites. Her research interests include understanding how
changes in the genome can affect both response to infection
and disease progression in humans, and virulence and
response to antimalarial drugs and other control methods
(e.g. vaccines) in the parasites. She is also interested in
developing tools to improve current malaria infection
diagnosis and surveillance
of parasites during malaria control interventions. She
has a strong background in molecular biology and
population genetics and genomics, and started to
apply these skills to M. tuberculosis, and Zika and
Dengue virus pathogen genomes. Selected projects
include:
 Exploring the genetic diversity of human
malaria parasites through whole genome
sequencing and developing diagnostic and
molecular barcoding tools.
SNPs in P. falciparum organelles
 Investigating malaria in pregnancy: Are the
parasites sequestered in the placenta
genetically different?
 Understanding the genetic diversity of P. vivax in Brazil and recrudescent/ reinfection during pregnancy.
Selected publications
1. Genomic variation in two gametocyte non-producing P. falciparum clonal lines. Benavente
ED, et al. Malaria Journal 2016.
2. Genomic epidemiology of artemisinin resistant malaria. MalariaGEN Elife 2016.
3. K13-propeller polymorphisms in P. falciparum parasites from sub-Saharan Africa. Kamau E,
et al. J Infect Dis 2015.
4. A barcode of organellar genome polymorphisms identifies the geographic origin of
Plasmodium falciparum strains. Preston MD, et al. Nature Comm 2014.
5. Analysis of P. falciparum diversity in natural infections by deep sequencing. Manske M, et al.
Nature 2012.
http://www.lshtm.ac.uk/aboutus/people/campino.susana
P a g e 20 | 30
Johannes Dessens
Senior Lecturer in Parasite Cell Biology
Research in Johannes Dessens’ lab focuses on the molecular
and cell biological characterisation of malaria parasite genes, in
particular those expressed in the mosquito stages: ookinetes,
oocysts and sporozoites, with the aim to discover new rational
ways to reduce parasite transmission. Successful research
projects involve studies of a family of LCCL-domain adhesive
proteins (LAPs); and a family of cytoskeletal intermediate
filament proteins (alveolins). We have shown that LAPs are
targeted to the crystalloids, unique multivesicular organelles found uniquely in
ookinetes and young oocysts. LAP depletion abolishes crystalloid biogenesis and
sporozoite transmission, identifying the crystalloid as a key organelle in sporogonic
development. Alveolins are targeted to a unique cortical structure, the subpellicular
network (SPN), in merozoites, ookinetes and sporozoites, and alveolin depletion gives
rise to morphological abnormalities and reduced motility, tensile strength and
infectivity. We have shown that alveolin domains are composed of tandem repeat
sequences with a 12 amino acid periodicity.
Cultured P. berghei ookinetes expressing a GFP-tagged alveolin (left), and a
GFP-tagged LAP (right), serving as fluorescent markers for the SPN and
crystalloids, respectively.
Selected publications
1. Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and
transmission of the malaria parasite. Santos JM, et al. Proc Natl Acad Sci USA 2016.
2. Biogenesis of the crystalloid organelle in Plasmodium involves microtubule-dependent
vesicle transport and assembly. Saeed S, et al. Int J Parasitol 2015.
3. Plasmodium alveolins possess distinct, but functionally and structurally related multi-repeat
domains. Al-Khattaf FS, et al. Parasitol Res 2015.
4. PbSR is synthesized in macrogametocytes and involved in formation of the malaria
crystalloids. Carter V, et al. Mol Microbiol 2008.
5. A malaria membrane skeletal protein is essential for normal morphogenesis, motility and
infectivity of sporozoites. Khater EI, et al. J Cell Biol 2004.
www.lshtm.ac.uk/aboutus/people/dessens.johannes
P a g e 21 | 30
Course Director for MSc in Medical Microbiology
Nick Dorrell
Senior Lecturer in Bacterial Pathogenesis
Nick Dorrell’s current research interests cover five main areas
of bacterial pathogenesis relating to the human pathogen
Campylobacter jejuni. Studies into the regulation of C. jejuni
gene expression have identified RrpA and RrpB as
transcriptional regulatory proteins with a role in controlling
peroxide and aerobic stress responses. An investigation into
the role of bacterial outer membrane vesicles (OMVs) in C.
jejuni pathogenesis has shown that C. jejuni OMVs alone are
capable of inducing a host innate immune response and possess proteolytic activity.
Investigations into the mechanisms of C. jejuni invasion of intestinal epithelial cells are
focusing on the role of the fibronectin-binding proteins CadF and FlpA. Recent studies
are also focusing on the role of the C. jejuni Type VI Secretion System. Also
investigations into the innate immune response to C. jejuni infection in collaboration
with Mona Bajaj-Elliott (UCL Institute of Child Health) have identified novel bacterial
interactions with the host immune system.
Current research focuses on:





Role of outer membrane vesicles during C. jejuni infection;
C. jejuni oxidative and aerobic stress responses;
Mechanisms of C. jejuni invasion of intestinal epithelial cells;
Role of the C. jejuni Type VI Secretion System;
The innate immune response to C. jejuni infection.
Selected publications
1. Campylobacter jejuni outer membrane vesicle-associated proteolytic activity promotes
bacterial invasion by mediating cleavage of intestinal epithelial cell E-cadherin and occludin.
Elmi et al. Cell Microbiol 2016.
2. The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence
bacterial responses to oxidative and aerobic stresses. Gundogdu, et al. Front Microbiol 2015.
3. Campylobacter jejuni lipooligosaccharide sialylation, phosphorylation, and amide/ester
linkage modifications fine-tune human Toll-like receptor 4 activation. Stephenson, et al. J Biol
Chem 2013.
4. Campylobacter jejuni outer membrane vesicles play an important role in bacterial
interactions with human intestinal epithelial cells. Elmi, et al. Infect Immun 2012.
5. Increase in Campylobacter jejuni Invasion of Intestinal Epithelial Cells under Low-Oxygen
Coculture Conditions That Reflect the In Vivo Environment. Mills, et al. Infect Immun 2012.
http://www.lshtm.ac.uk/aboutus/people/dorrell.nick
P a g e 22 | 30
Richard Stabler
Senior Lecturer of Molecular Bacteriology
Richard Stabler’s research interests include the genomic
analysis of bacterial pathogens with a current focus on the
genetics and transmission of antibiotic resistance.
He has exploited emerging technologies, initially genome
microarrays but more recently high throughput sequencing
technology (HTST) and nanopore technologies (MinION) for
molecular epidemiology and identification of genes involved
in virulence. He is currently the antimicrobial resistance lead
for the school and runs the AMR interest group. Additionally, he is also the LSHTM
space business manager due to his links with the European Space Agency.
Current research focuses on:
 The global population of Clostridium difficile RT023 and Acinetobacter baumannii,
 Hospital and community transmission of Methicillin Resistant Staphylococcus
Aureus (MRSA) in South London,
 Identifying drug resistance and virulence factors from
A. baumannii,
 The potential role of bacteriophage depolymerases
as therapy for A. baumannii infection,
 Investigating the genetics essential for colonisation
and dissemination of Escherichia coli K1 in neonatal
meningitis,
 The role of pharyngeal commensals with the
development of highly drug resistant Neisseria gonorrhoea,
 Analysis of the effect of a Gravity Loading Countermeasure SkinSuit on the natural
bacterial skin flora.
Selected publications
1. Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of
MRSA isolates in south-east London. Hughes J, et al. J Antimicrob Chemother 2015.
2. Genomic Epidemiology of a Protracted Hospital Outbreak Caused by a Toxin A-Negative
Clostridium difficile Sublineage PCR Ribotype 017 Strain in London, England. Cairns MD, et
al. J Clin Microbiol 2015.
3. The Genotoxin Colibactin Is a Determinant of Virulence in Escherichia coli K1 Experimental
Neonatal Systemic Infection. McCarthy AJ, et al. Infect Immun 2015.
4. Staphylococcal phenotypes induced by naturally occurring and synthetic membraneinteractive polyphenolic β-lactam resistance modifiers. Palacios L, et al. PLoS One 2014.
5. Draft Genome Sequences of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii
BS8, Soil Bacteria That Cooperate To Degrade the Poly-γ-d-Glutamic Acid Anthrax Capsule.
Stabler RA, et al. Genome Announc 2013.
www.lshtm.ac.uk/aboutus/people/stabler.richard
P a g e 23 | 30
Martin Taylor
Senior Lecturer in Molecular Biology
Martin Taylor is interested in nutrient uptake and utilisation in
Kinetoplastids. His recent work has focused principally on iron
and ascorbate (vitamin C). Iron is a crucial nutrient for a variety
of pathogenic organisms and can
be sequestered by the innate
immune system. Martin’s work is
centred on the mechanisms used
by kinetoplastid parasites to
obtain iron in their mammalian host. His primary interest
is in the African and American trypanosomes, T. brucei
and T. cruzi. T. brucei being extracellular in the mammal
of
Luciferaseobtains non-heme iron from transferrin by endocytosis. Expression
mNeon GFP fusion protein
The roles of various proteins in this uptake are currently (green) in Trypanosoma cruzi.
being
analysed This allows us to follow infection
in mice and at the cellular level
using a variety of in tissues.
techniques
including
RNA
interference,
conditional null mutants, drug assays and
fluorescence based assays for intracellular iron
levels. He has created a conditional expression
system for the American trypanosome which will
be used to characterise iron uptake pathways in
Our current model of iron trafficking in the
this intracellular parasite. Martin is also involved
blodstream form trypanosome. Incoming
in developing highly sensitive in vivo imaging
ferric iron is reduced by Cyb561 to ferrous
iron. This is transported across the
models for drug discovery programmes and
membrane by MLP.
pathogenesis studies for Human African
Trypanosomiasis (Sleeping Sickness), Chagas disease and visceral leishmaniasis.
Selected publications
1. Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and
chronic cardiomyopathy. Lewis MD, et al. Cell Microbiol 2016.
2. The Trypanosoma cruzi Vitamin C Dependent Peroxidase Confers Protection against
Oxidative Stress but Is Not a Determinant of Virulence. Taylor MC, et al. PLoS Negl Trop Dis
2015.
3. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei.
Shameer S, et al. Nucleic Acids Res 2015.
4. Highly Sensitive In Vivo Imaging of Trypanosoma brucei Expressing “Red-Shifted”
Luciferase. McLatchie AP, et al. PLoS Negl Trop Dis 2013.
5. Evidence that transport of iron from the lysosome to the cytosol in African trypanosomes is
mediated by a mucolipin orthologue. Taylor MC, et al. Mol Microbiol 2013.
www.lshtm.ac.uk/aboutus/people/taylor.martin
P a g e 24 | 30
Teresa Cortes
Lecturer in Microbiology
Teresa Cortes is funded by a Starting Grant from the European
Research Council. She is primarily interested in investigating how
translational regulation contributes to biological adaptation in the
human pathogen Mycobacterium tuberculosis, the causative agent
of human tuberculosis. As well as causing tuberculosis, M.
tuberculosis can persist in an individual host for decades in an
asymptomatic state, with one third of the world population
estimated to be latently infected. The mechanisms underlying this
persistence in the host are still poorly understood. Furthermore, the emergence of drug
resistant tuberculosis makes the development of effective new treatments an urgent
challenge. Understanding the ability of M. tuberculosis to switch between replicating
and non-replicating states during infection and disease is central to the search for
improved treatments.
Recent findings suggest that ‘specialised ribosomes’ can
preferentially translate different mRNA subsets, particularly
in response to stress. mRNA molecules contain specific
signals that optimise their interaction with ribosomes; known
as leader sequences, these include the Shine-Dalgarno
(SD) sequence required for canonical translation initiation in
bacteria. Teresa’s previous research recently demonstrated
that M. tuberculosis expresses an unexpected number of leaderless mRNA transcripts
that lack the SD sequence. In Escherichia coli, only a few leaderless transcripts have
been described and they are selectively translated by specialised ribosomes. Teresa’s
group is using cutting-edge experimental techniques combined with bioinformatics
analysis to investigate the role of translation regulation in the adaptive response of M.
tuberculosis and its contribution to differential susceptibility to drugs that target
ribosomal activities.
Selected publications
1. Genome-Wide Mapping of Transcriptional Start Sites Defines an Extensive Leaderless
Transcriptome in Mycobacterium tuberculosis. Cortes T, et al. Cell Rep 2013.
2. Transcription and translation of the rpsJ, rplN and rRNA operons of the tubercle bacillus.
Cortes T and Cox RA. Microbiology 2015.
3. Genomic mapping of cAMP Receptor Protein (CRP Mt) in Mycobacterium tuberculosis: relation
to transcriptional start sites and role of CRPMt as a transcription factor. Kahramanoglou C, et
al. Nucleic Acids Res 2014.
4. Mapping of genotype-phenotype diversity amongst clinical isolates of Mycobacterium
tuberculosis by sequence-based transcriptional profiling. Rose G, et al. Genome Biol Evol
2013.
5. A small RNA encoded in the Rv2660c locus of Mycobacterium tuberculosis is induced during
starvation and infection. Houghton J, et al. PLoS One 2013.
http://www.lshtm.ac.uk/aboutus/people/cortes.teresa
P a g e 25 | 30
Jon Cuccui
Lecturer in Molecular Bacteriology
Jon Cuccui has a long standing interest in bacterial
glycosylation systems. His initial work at LSHTM using
signature tagged mutagenesis in Burkholderia pseudomallei,
the causative agent of melioidosis, revealed that the capsular
polysaccharide was
a major virulence
determinant. This
research led to
improved understanding and exploitation of
polysaccharides as vaccine components. He
was recently involved in the generation and
sequencing of a million mutant transposon
(TraDIS) library of B. pseudomallei which Principles of protein glycan technology in E. coli.
revealed novel essential genes and targets
for antimicrobial development. Understanding bacterial glycosylation systems can
reveal why they evolved and were maintained, and secondly, how they can potentially
be exploited as novel biotechnological tools. Jon Cuccui is involved in using in vivo
glycosylation systems, termed ‘protein glycan coupling technology’ (PGCT) in order to
assemble glycoconjugate vaccines. He developed a first generation glycoconjugate
vaccine against the Gram negative bacterium, Francisella tularensis, the causative
agent of tularemia for which no licensed vaccine currently exists. PGCT has been
subsequently used to generate vaccines against the human pathogens B.
pseudomallei and Streptococcus pneumoniae. More recently he has been developing
novel genetic tools to expand the utilisation of PGCT to subunit vaccine generation
against animal pathogens. He is funded by a Wellcome Trust/LSHTM fellowship to
identify and overcome glycoengineering bottlenecks in order to expand the capabilities
of PGCT. He is also studying the N-linked glycosylation system in the porcine
pathogen A. pleuropneumoniae and attempting to unravel its biological function and
potential application.
Selected publications
1. Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in
Escherichia coli. Kay EJ, et al. Open Bio. J. 2016. Epub 2016.
2. Functional analysis of N-linking oligosaccharyl transferase enzymes encoded by deep-sea
vent proteobacteria. Mills DC, et al. Glycobiology 2016.
3. Exploitation of bacterial N-linked glycosylation to develop a novel recombinant
glycoconjugate vaccine against Francisella tularensis. Cuccui J, et al. Open Biol 2013.
4. Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts
essential genes and novel targets for antimicrobial development. Moule MG, et al. MBio 2014.
www.lshtm.ac.uk/aboutus/people/cuccui.jon
P a g e 26 | 30
Lisa Dawson
Lecturer
Lisa Dawson sits on the Senate and Athena swan committee. She is also
a member of the exam board for the Medical Microbiology and Molecular
Biology of Infectious Diseases MSc courses and a tutor for both Distance
Learning MSc and Medical Microbiology MSc courses. She supervises
both PhD and MSc research projects based at LSHTM. Her research
interests also include Mycobacterium tuberculosis. She undertook a PhD
at the National Institute for Medical Research, in which Lisa studied the
regulation of DNA damage repair in Mycobacterium tuberculosis.
The main focus of the research is the characterisation of the genetic and
phenotypic traits of the pathogenic bacteria, including Clostridium difficile
using a genome to phenome approach. Clostridium difficile is the most frequent cause of
antibiotic associated nosocomial diarrhoea world-wide. Antibiotic therapy for an underlying
condition disrupts the normal gut microflora and increases the risk of colonisation with C.
difficile. The recent transcontinental spread of C. difficile hypervirulent lineages has been
associated with high recurrence rates, increased levels of mortality and severe hospital
outbreaks. Nevertheless, little is known about the mechanisms involved in colonisation of
the gut and reactivation of disease. Current treatment regimes have varied efficacy and
relapse rates are high, therefore C. difficile infection (CDI) remains a challenge to the
healthcare industry. Lisa Dawson’s research interests are bacterial biofilms, which are
recognised in other pathogens as vital for colonisation,
persistence and virulence in a host. She has shown that C.
difficile is capable of forming biofilms in-vitro and is interested
in the mechanisms behind biofilm formation. C. difficile
possesses a number of virulence traits; among them is the
unique ability to produce para-cresol, a bacteriostatic
phenolic agent. Lisa is currently involved in characterising
the production of p-cresol by C. difficile and identifying the
effect this has on modulation of the intestinal microbiome, Biofilm formed by C. difficile in-vitro
using 16s rRNA sequencing.
Selected publications
1. Cyclic-di-GMP regulates production of sortase substrates of Clostridium difficile and their surface
exposure through ZmpI protease-mediated cleavage. Peltier J, et al. J Biol Chem 2015.
2. Clostridium difficile has a single sortase, SrtB, that can be inhibited by small-molecule inhibitors.
Donahue EH, et al. BMC Microbiol 2014.
3. Clostridium difficile spo0A gene is a persistence and transmission factor. Deakin LJ, et al. Infect
Immun 2012.
4. Characterisation of Clostridium difficile Biofilm Formation, a Role for Spo0A. Dawson LF, et al.
PLoS One 2012.
5. The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains.
Dawson LF, et al. BMC Microbiol 2011.
http://www.lshtm.ac.uk/aboutus/people/dawson.lisa
P a g e 27 | 30
Nicholas Furnham
Lecturer and MRC Methodology Research Fellow
Nicholas Furnham’s research interests can be divided into
gaining a fundamental understanding of the evolution of novel
protein functions and the applications of the findings to
important questions in infectious disease biology, in particular
antimicrobial resistance and
A
the development of novel
therapeutics.
Using
an
interdisciplinary
approach
combining
biology
and
chemistry
with
computer
science his group develops new algorithms and
bioinformatics tools through large-scale integrative
data processing.
Current research focuses on understanding the
evolution of novel protein Afunctions and applying this
B
understanding to a diverse range of projects including:
molecular consequences of genomic variance from
GWAS studies in surveillance and tracking of
antimicrobial resistance
pharmacogenomics combined with high-content
screening for drug repurposing in neglected tropical
diseases
putting allergy into its evolutionary context by
IgE
IgG
establishing molecular similarities between known
Predicting and testing IgE inducing
allergens and proteins in multicellular parasites.
Schistosoma
worm
B
IgE ng/ml
Brich
Pollen
Brich Pollen
Schistosoma
Conservation
Quality
Conservation
1e+03
1e+03
1e+02
1e+02
1e+01
1e+01
IgG ug/ml
1e+00
1e+00
1e+01
1e+01
1e−01
1e−01

Brich Pollen
Schistosoma
1e−01
1e−01
1e+00
1e+00

IgETC[,
ng/ml
TC[, 1]
1]
1e+02
1e+02

Schistosoma
worm
1e+03
1e+03
Brich
Pollen
betv1_ige0B
betv1_ige0B
betv1_igg10B
betv1_igg10B
TC[,
TC[,2]
2]
Quality
epitopes in Schistosoma mansoni
worms
Selected Publications:
1. Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.
Tyagi N, et al. PLoS Computational Biology 2015.
2. FunTree: advances in a resource for exploring and contextualising protein function
evolution. Sillitoe I, et al. Nucleic Acids Res 2016.
3. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling
provides insights into anti-tuberculosis drug resistance. Phelan J, et al. BMC Medicine 2016.
4. Large-Scale Analysis Exploring Evolution of Catalytic Machineries and Mechanisms in
Enzyme Superfamilies. Furnham N, et al. Journal Molecular Biology 2016.
5. EC-BLAST: a tool to automatically search and compare enzyme reactions. Rahman SA, et al.
Nature Methods 2014.
http://www.lshtm.ac.uk/aboutus/people/furnham.nick
P a g e 28 | 30
IgE
I
Michael Gaunt
Lecturer in Genome Parasitology
The work focused on using evolutionary models to
understand the molecular epidemiology or “microevolution”
and “macroevolution” of the parasite Trypanosoma cruzi the
causative agent of South American trypanosomiasis and its
insect vector triatomine bugs.
Microevolution: T. cruzi is a zoonose and the genetic
relationship, or “population structure”, between sylvatic
mammals and human reservoir hosts could have important
public health implications. The team have developed a
population genomics method using “microsatellite” genetic markers that provide the
most accurate typing tool available for T. cruzi. The application of this tool to field
isolates demonstrates T. cruzi has a complex epidemiology. For example, some
ecotopes show a close genetic association between sylvatic hosts (rodents) and
humans but other ecotopes (opossums) show a mixture of close and distant genetic
associations. The microsatellites panel identified multiclonal infections as being much
more important than previously thought.
Macroevolution: Evolutionary studies on triatomine bugs revealed the insect evolved
blood-feeding behaviour once and this occurred exactly at the same time as the
formation of South America. Finally, theoretical work on evolutionary models reveals
that several commonly used assumptions (mutation matrices) may result in erroneous
epidemiological inferences. Refining these models provides new epidemiological
insights.
Selected publications
1. Recent, independent and anthropogenic origins of Trypanosoma cruzi hybrids. Lewis MD, et
al. PLoS Negl Trop Dis 2011.
2. Phylogenetic multilocus codon models and molecular clocks reveal the monophyly of
haematophagous reduviid bugs and their evolution at the formation of South America.
Patterson P and Gaunt M, Mol Phyl Evol 2010.
3. Genome-scale multilocus microsatellite typing of Trypanosoma cruzi discrete typing unit I
reveals phylogeographic structure and specific genotypes linked to human infection.
Llewellyn M, et al. PLoS Pathog 2009.
4. Trypanosoma cruzi IIc: phylogenetic and phylogeographic insights from sequence and
microsatellite analysis and potential impact on emergent Chagas disease. Llewellyn M, et al.
PLoS Negl Trop Dis 2009.
www.lshtm.ac.uk/aboutus/people/gaunt.michael
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Esmeralda Valiente
Lecturer in Molecular Microbiology
Esmeralda Valiente was awarded a Marie Curie Intraeuropean
Fellowship for career development. Esmeralda’s main interests
include investigating new glycosylation systems in Clostridium
difficile and various Vibrio species (in particular Vibrio cholerae
O1 El Tor), and their potential role in bacterial virulence.
Glycosylation is known to impart novel physical and biological
roles to proteins in eukaryotes that can be grouped into two
general categories, providing labels for protein recognition and
for protein stabilization. In bacteria, protein glycosylation often has important roles in
the survival and pathogenesis of bacteria and thus represent an ideal target to disable
bacteria.
Her studies were recently extended from C. difficile to
Vibrio cholerae and other Vibrio species as part of a
Wellcome Trust-funded collaboration with Professor
Anne Dell’s group at Imperial College London.
Esmeralda also collaborates with Professor Gordon
Dougan and Nicholas Thompson at the Wellcome Trust
Sanger Institute where Vibrio cholerae transcriptome
and proteome analyses are conducted.
Electron microscopy image of the
bacterial pathogen Vibrio cholerae
showing its polar flagellum.
Selected publications
1. The Clostridium difficile PCR ribotype 027 lineage: a pathogen on the move. Valiente E, et al.
Clin Microbiol and Infect 2014.
2. The post-translational modification of the Clostridium difficile flagellin affects motility, cell
surface properties and virulence. Faulds-Pain A, et al. Mol Microbiol 2014.
3. Emergence of new PCR-ribotypes from the hypervirulent Clostridium difficile 027 lineage.
Valiente E, et al. J. Med. Microbiol 2012.
4. Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides
insight into the evolution of a hypervirulent bacterium. Stabler RA, et al. Genome Biol 2009.
5. Role of the metalloprotease Vvp and the virulence plasmid pR99 of Vibrio vulnificus serovar
E in surface colonization and fish virulence. Valiente E et al. Env. Microbiol 2008.
www.lshtm.ac.uk/aboutus/people/valiente.esmeralda
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