Steve Paterson's Projects
If you're interested in collaborating, please feel free to contact me.
Paterson, Wit (Lancaster), Hopkins (Edinburgh), Pemberton
(Edinburgh), Piertney (Aberdeen), Slate (Sheffield) and Viney (Bristol)
-- A lifetime of attrition; post-genomic analysis of ecological and
evolutionary processes in nematode-vertebrate systems.
Funding Natural Environment Research Council (£1.2M, of which
£390k to Liverpool) 2006-2009. Staff at Liverpool; Dr Helen Evans
(PDRA) and Lu Mello (P/T PDRA)
Abstract: Virtually every species of terrestrial, freshwater and marine
vertebrate is parasitised by nematodes (roundworms). Nematode
infections exhibit persistent infection and re-infection throughout the
life of a host, with strong sex, age and season effects on intensities
of infection. These parasites therefore constitute an important
component of the environment of vertebrates and affect the fitness of
individuals and the dynamics of populations. There is now a timely
opportunity to apply new methods from genomics to explore the
ecological and evolutionary consequences of vertebrate-nematode
interactions in the natural environment. Such work holds great promise,
but extending genomics from the bench-top to natural populations also
presents significant challenges. In particular, the variation between
individuals that makes research in natural populations so important
also makes it difficult to apply some genomics methods, such as high
throughput gene expression (microarray) analyses.
Our response to these challenges is to build a consortium based around
three well-characterised vertebrate - nematode systems, the Soay sheep
and Teladorsagia circumcincta,
the red grouse and Trichostrongylus tenuis and the brown rat and Strongyloides ratti. We will use a
series of approaches ranging from microarray studies within laboratory
experiments that mimic the wild situation, through to microarray
studies on individuals living in wild populations subject to
experimental manipulations. As a result, we hope to learn from each
other, and demonstrate to the research community, just how far these
new methodologies can be applied to natural populations in situ. In the
process, we expect to generate a trained group of workers with the
skills to develop the field more widely in the UK.
Work within the consortium will explore a set of specific objectives
that, in combination, allow us to address two general objectives that
are crucial to advancing our understanding of host-parasite ecology and
evolution:
(1) To dissect and quantify the link between the genetic basis of
host-parasite interactions and the population biology of hosts and
parasites.
Infection is a process that acts on individuals but impacts on the
dynamics of populations, through the effects of infection on the
growth, survival and reproduction of individuals. Equally, the density
of a population will impact on the level of competition between
individuals for food or mates and consequently on the condition of
individuals and their susceptibility to infection. The key challenge
now is to understand how individual processes of infection influence,
and are influenced by, the population biology of hosts and parasites.
(2) To examine the origins and maintenance of genetic diversity in host
and parasite populations.
Within a population, individual hosts exhibit genetic differences in
their susceptibility to infection. Equally, populations of parasitic
nematodes are genetically variable with consequences for the
persistence and transmission of infection. The key challenges to be
addressed now are to identify regions of vertebrate and nematode
genomes where genetic diversity is maintained through the continued
interaction between both antagonists, the consequences of this genetic
diversity and the selective processes by which this diversity is
maintained.
Links: Ernst Wit,
John Hopkins, Josephine
Pemberton, Stuart
Piertney, Jon
Slate and Mark
Viney. NERC
Post-genomics and proteomics programme and NERC molecular genetics
facility.
Cossins and Paterson, Datamining pipelines for the unbiased interpretation of large-scale microarray datasets in environmental research using non-model species
Funding NERC, £200k, 2008-2010, PDRA Ajanthah Sangaralingam
Abstract.: The general problem we address is to turn lists of differentially expressed genes from large-scale microarray data-sets into more intuitive clusters of genes annoated by gene function. Many of the tools needed to do this – such as co-expression and gene set meta-analyses – have only recently become available and so there is a timely opportunity to support late stage NERC awards. Our objective is to bundle these existing tools into pipelines that can rapidly analyse expression data from non-model organisms of environmental interest. In doing so, we will add value to, and produce extra publications from, existing NERC data-sets.
Links: Andrew Cossins and Liverpool Microarray Facility.
Paterson and Hall, Sequencing genetic diversity in host and parasite genes using the ultra-high throughput 454 GS-Flex platform
Funding NERC, £126k, 2008 - 2009
Summary: This proposal will exploit recent advances in ultra high throughput sequencing to assay genetic diversity across thousands of host and parasite genes. This allows us to perform a radically new and powerful analysis to test the prediction that the genes that are most polymorphic in a population are those involved in host-parasite interactions.
Links: Neil Hall and Liverpool Advanced Genomics Facility
Hall, Clarke and Paterson, Single nucleotide polymorphism analysis of population structure and virulence in E. histolytica
Funding, The Wellcome Trust , £268k, 2008-2011, PDRA Gareth Weddel
Begon, Paterson, Birtles and Bradley, Immunodynamics of field voles
Funding, NERC, £600k, 2007 - 2010
Andrew Turner, PhD student (NERC) with Prof. Mike Begon
Abstract: This project will examine the molecular basis of resistance
to infectious disease in natural vertebrate populations. The specific
objective of this project is to determine whether cytokine
polymorphisms are associated with
resistance to a range of pathogens in a natural population of field
voles. Cytokines are signalling molecules that control the relative
activity of different components of the vertebrate immune system and so
are chosen as the focus of this project. Genetic variation within the
genes that code for these molecules is often associated with
differences in levels of gene expression and with differences in
resistance to specific pathogens. Importantly, this project will go
beyond a simple 'immunocompetent' view of the immune system. Different
aspects of the immune system, such as the activation of either type 1
or type 2 T-helper cell subsets (known as Th1 and Th2 responses,
respectively) are associated with effective immune clearance of
microparasites (Th1 responses) or macroparasites (Th2 responses). We
therefore predict, and will test for, cytokine polymorphisms that
exhibit a trade-off between resistance to microparasites and
susceptibility to macroparasites, or vice versa. In genetics, this kind
of trade-off is known as antagonistic pleiotropy and can act to
maintain genetic polymorphism within a variable environment. The random
exposure of an individual to varied types of pathogen provides just
such an environment and may explain the high levels of polymorphism
commonly found at immune function genes. Another possible mechanism for
antagonistic pleiotropy is where a genotype protects an individual
following exposure to an infection but reduces survivorship or
fecundity in the absence of an infection. This may be likely given that
many immune responses induce pathology, such as inflammatory reactions,
that are harmful to host tissue.
Links: Prof.
Mike Begon, University of Liverpool
Tara Mangal, PhD student (UoLiverpool) with Dr. Andrew Fenton
Abstract: This project will examine the environmental, and other,
influences on life-history traits in the trematode Schistosoma mansoni
and its snail host Biomphalaria glabrata. Schistosomes infect around
200m people worldwide with a further 400m at risk of infection. Climate
change is likely to have important consequences on the reproduction and
survival of both schistosomes and their hosts, with consequences for
the population dynamics of both speciees and for the force of
transmission within endemic areas. This project will take a combination
of both laboratory studies and parameterised epidemiological models to
investigate these issues.
Links: Dr.
Andrew Fenton, University of Liverpool; Prof. Mike
Doenhoff, University of Nottingham.
Previous projects
Viney (Bristol) and Paterson -- Immuno-epidemiology of nematode infections: the causes and consequences of density-dependent interactions
Funding Wellcome Trust (£350k), 2004 - 2007. Staff -- Dr. Colin Bleay (PDRA) and Clare Wilkes (PGRA)
Abstract: Nematodes are important pathogens of humans and other animals. Nematode populations are regulated by density-dependent effects. Understanding the basis of these effects is fundamental to a mechanistic understanding of nematode infection and epidemiology. We have recently developed a novel methodology in Strongyloides ratti that demonstrates, for the first time, that density-dependent effects on survivorship and fecundity are dependent on the host immune response. These findings raises further questions that we propose to address. These are: (1) How wide-spread is the phenomenon of immune-dependent, density-dependence in other parasitic nematodes? (2) Are there parasitic nematode, inter-specific, density-dependent effects? (3) What is the immunological basis of density-dependent effects? (4) What are the epidemiological consequences of these density-dependent effects?
Links: Prof. Mark Viney
Begon, Bennett, Birtles, Paterson and Lambin -- The dynamics of, and risks posed by, concomitant zoonotic infections in their wildlife reservoirs
Funding Wellcome Trust (£385k) 2005 - 2008. Staff -- Dr. Sandra Telfer (PDRA)
Abstract: The core aim of this research will be to further undertanding of the dynamics of zoonotic infection within wildlife reservoirs. We will acheive this aim by collecting extensive data from replicate cyclic rodent populations, which will be added to further data and archived material from the same populations. Crucially, the project will examine not a single parasite but several. Thus, by investigating pathogens with a range of known biologies, we will test the hypothesis that detectable differencs in dynamics between pathogens can be related to diffferences in the pathogens' ecologies. This in turn will allow the zoonotic risk posed by contrasting types of pathogens to be assessed, along with the sensitivity of risk of key parameters. We will test the hyppothesis that the dynamics of any pathogen -- and the consequences of these dynamics for zoonootic risk -- depend not only on its interactions with its host but also on those with other, co-existing pathogens.
Links: Veterinary pathology at University of Liverpool, Jerzy Behnke (University of Nottingham)
Paterson -- Life history trade-offs in parasitic nematodes: constraints on infections and disease?
Funding Wellcome Trust (£140k), 2004 - 2007. Staff -- Becci Barber (Technician)
Abstract: This proposal will test the application of life-history theory to parasitic nematodes and provide a novel analysis of the natural constraints on nematode infection. Thus, the persistence of a nematode infection depends on the survivorship of adult worms inside the host and the transmission of infections between hosts depends on the fecundity of these worms. An important prediction from life-history theory is there should be a trade-off between current fecundity and future survivorship (and between other, related life-history traits). We will, for the first time, test this prediction in parasitic nematodes. Another prediction from life-history theory is that life-history traits, and the trade-offs between them, should vary in different environments. For parasitic nematodes, a major component of their environment is the immune response of their host. Host immune responses certainly reduce the survivorship and fecundity of nematode infections but do they also affect the trade-off between these traits?
We will test these two predictions using a rat-nematode system (Strongyloides ratti). We will use a selection regime to test for trade-offs between current fecundity and future survivorship (and between other, related life-history traits) and determine the effect of the host immune environment on these trade-offs.
Amy Sherborne, PhD Student (NERC) with Prof. Jane Hurst
Abstract: This project will examine the functional consequences of sequence divergence between individuals at MHC genes for immune function, parasite burden and behaviour. We will use semi-natural populations of house mice maintained at the Vet School. Using wild mice, as opposed to lab strains, allows us to examine selection pressures acting on the MHC within the context of their natural ecology. We will (i) determine the nucleotide sites that are subject to adaptive, positive selection in wild mice using population genetic analysis, (ii) assay the consequences of positive selection at these sites for the immune function and parasite burden of different MHC types, (iii) assay any behavioural preferences associated with MHC variation. We will test the hypothesis that sites under strong positive selection mediate strong patterns of variation between individuals in immune function and parasite burden. We will also test the hypothesis that these sites lead to odour-based differences and disassortative mating preferences.
Links: Animal Behaviour Group, Veterinary Sciences, University of Liverpool
Stephanie Gebert, PhD Student (NERC) with Prof. Mike Begon
Abstract: This project will examine the processes shaping the helminth communities of field voles, and wider interactions between micro- and macroparasite infections. Different arms of the immune response are adapted to clear or contain infection from these two very different kinds of parasites. These two different types of immune responses, Th1and Th2 mediated, are mutually down-regulatory and may mediate either antagonistic or synergistic interactions between helminth parasites, or between helminth parasites and microparasites. How do these mechanistic interactions within an individual shape the infection history of an individual host, or the parasite community of a host population? What consequences do the interactions between different kinds of parasite have for the emergence of zoonotic disease? We also note the invaluable help given by Prof. Jerzy Behnke (Nottingham) in this project.
Jenny Crossan, PhD Student (NERC) with Dr. Andrew Fenton
Abstract: This project will look at the behavioural ecology of
macroparasites,
examining the host-parasite interaction at the individual level to
determine how natural selection shapes the optimal infection
strategies. Jenny uses a well-established protocol for
quantifying many parasite life history traits using a convenient
laboratory system involving the entomopathogenic nematode Steinernema feltiae and its host,
the greater waxmoth Galleria
mellonella. By carrying out a series
of selection experiments using this system, she will quantify the
nature of the trade-offs influencing transmission success and assess
the co-variation of a number of life history traits under different
selection pressures.
Links: Dr.
Andrew Fenton (Liverpool)
Paterson and Boots (Sheffield) -- Modelling the mechanisms driving
parasite adaptation and diversity.
Funding Leverhulme Trust (£56k), 2003 - 2005. Staff -- Dr.
Ruth Hamilton (PDRA)
Abstract: This project uses deterministic and stochastic models to
achieve two objectives (1) Determine the consequences of host genetic
diversity and of immunological memory for the evolution and genetic
diversity of parasite populations and (2) Determine the potential for
the genomes of different types of parasite to adapt to host genotype
and immune responses. Our approach utalises the body of data available
on the molecular basis of presentation of parasite peptides by
host MHC molecules and the extraordinary diversity of MHC molecules in
natural populations. How does this host diversity affect the evolution
of diversity in parasites? Should parasites evolve to be generalists or
specialists with respect to their capacity to infect hosts of different
genotypes?
Links: Dr.
Mike Boots