Professor Mark Field
Research description
We have the general aims of elucidation of fundamental cell biology in trypanosomes and placing these in both disease-related and evolutionary contexts. There are three major goals:
- To identify and exploit novel aspects of the biology of protozoan parasites for therapy,
- To understand protein processing events in trypanosomes and how these relate to disease, and
- To reconstruct the evolutionary history of the intracellular trafficking machinery
Within this are several projects directed towards uncovering of gene function using RNA interference (RNAi), cell biology to understand how trypanosomes build and maintain their cell surface, acquire nutrients and evade the immune system. Additionally we use in silico methods for evolutionary cell biology.
Our main experimental model, Trypanosoma brucei is the causal agent of sleeping sickness in humans (1). Originally believed restricted to Africa, it recently emerged that T. brucei subspecies are present across Asia, with a huge economic and morbidity burden (2). Understanding how trypanosomes cause disease is poor and the drugs for treatment are primitive and becoming ineffective. Trypanosome research was revolutionized by the complete genome sequence and development of RNAi methods (3, 4). These advances allow rapid identification of gene products and functional investigation. We use these methods coupled to classical cell biology for localization, morphology and biochemical analysis, to provide the core of our work. We also use mammalian cells and Saccharomyces cerevisiae as models and are interested in developing tools to facilitate analysis of the parasite genome to accelerate gene discovery and functional analysis.
Our evolutionary interests focus on intracellular trafficking systems and nucleocytoplasmic transport. Recent advances indicate unexpected similarities between these two facets (5), and combining comparative genomics, phylogenetic analysis and direct functional assignment, frequently in trypanosomes, we are seeking to understand the origins of these systems.
Further reading
- Barrett MP. The rise and fall of sleeping sickness. Lancet 2006 367 1377-8
- Lai DH, et al., Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei. PNAS 2008 105 1999-2004
- Subramaniam C, et al., Chromosome-wide analysis of gene function by RNA interference in the african trypanosome. Eukaryot Cell 2006 5 1539-49
- Berriman M, et al., The genome of the African trypanosome Trypanosoma brucei. Science 2005 309 416-22
- Devos D, et al., Simple fold composition and modular architecture of the nuclear pore complex. PNAS 2006 103 2172-7