Research overview

 

    Microbial eukaryotes (protozoa) represent a huge component of the biosphere, with contributions to ecology, food security and the environment. Parasitic diseases caused by protozoa constitute a major global threat. Our work melds several key aspects of protist biology, principally focusing on the parasitic organisms of the trypanosome group, but also extending into environmental organisms, such as the alga Euglena. We are active in comparative genomics and experimental cell biology, using these approaches to understand how eukaryotes have evolved, as well as to develop methodologies for the functional understanding of protist diversity and disease mechanisms. We are committed to open access publishing and rapid, full disclosure of data.
    In trypanosomes we study fundamental aspects of parasite biology to identify new therapeutic targets for clinical intervention, focusing on the African Trypanosome, Trypanosoma brucei, and specifically macromolecular transport, signaling and evolution. T. brucei is the causal agent of sleeping sickness in humans and livestock in sub-Saharan Africa, responsible for direct human suffering from disease and indirectly through uncountable hardship from the virtual absence of cattle within the range of the tsetse fly vector. Our understanding of how trypanosomes cause disease remains poor and the drugs used to treat infections are primitive. T. brucei also offers a superb model system with which to study disease mechanisms, drug interactions and the diversity of cell biology across the eukaryotes. We welcome interest from people in all of these areas.









The laboratory has three major inter-related areas of interest: 
Endocytotic systems of trypanosomes: The role of components of the endocytotic pathway in drug sensitivity, virulence in vivo and protein/lipid sorting mechanisms.
Nuclear architecture and function in trypanosomes: Analysis of the trypanosome nuclear pore complex and nuclear envelope, and impact on gene expression and virulence.
Evolutionary biology, eukaryogenesis, eukaryotic microbial diversity: Reconstructing the evolutionary history of intracellular transport pathways and origins of the eukaryotic cell though comparative genomics, genome sequencing and proteomics.

Long term collaborators include:
John Aitchison, Seattle Biomedical Research Institute, Seattle, USA,
Brian Chait, Laboratory of Gaseous Ion Chemistry, The Rockefeller University, New York, USA,
Joel Dacks, Department of Cell Biology, University of Alberta, Edmonton, Canada,
David Horn, Division of Biological Chemistry and Drug Discovery, Dundee, Scotland,
Julius Lukesˇ, University of Southern Bohemia, České Budějovice,
Miguel Navarro, Instituto de Parasitología y Biomedicina, Granada, Espania,
Michael Rout, Laboratory of Structural Cell Biology, The Rockefeller University, New York, USA.












Environment: Our laboratory encompasses tissue culture suites, state of the art proteomics, light and electron microscopy, together with informatics, offices and associated services. This environment allows interactions with molecular parasitologists, microbiologists, evolutionary biologists, immunologists and cell biologists, providing an excellent skills base and a lively intellectual atmosphere. The environment is unique in providing access to expertise and infrastructure for a large range of technologies directed towards the understanding of protists and the diseases they cause.
Training: We offer training in molecular biology including qPCR, Southern blotting, library screening, mutagenesis, heterologous expression in bacterial and eukaryotic systems, RNA interference (RNAi), tissue culture of mammalian cells and parasites, construction of transgenic parasites and analysis of virulence in vivo. We also can provide experience in immunochemistry, production of antibodies and immuno-purification, metabolic labeling, immuno-precipitation, protein chemistry including proteomics, liquid chromatography, SDS-PAGE, Western blotting and other methods. The laboratory has its own fluorescence microscope with access to high resolution fluorescence microscopy and electron microscopy as required. Finally, more specialized approaches, including mass spectrometry, genome sequencing, microarray and RNAseq analysis, software development (we very occasionally develop our own applications) and bioinformatics (including phylogenetics) all form part of our research portfolio.
The following agencies have supported our research: The Wellcome Trust, The Medical Research Council, The Biotechnology and Biological Sciences Research Council, The British Heart Foundation, The British Council, The Commonwealth and Cambridge Commonwealth Fund, The Nuffield Foundation, The Bill and Melinda Gates Foundation, The Royal Society, The British Association Millennium Fund, The Leverhulme Trust, The National Institutes of Health (USA), The Sandler Foundation, The Sichuan Academy of Sciences, the Higher Education Funding Council for England and the Scottish Higher Education Funding Council.