Professor Derek Nolan

I have worked on African trypanosomes, which cause human sleeping sickness, for twenty years. As a PhD student I investigated the bioenergetics of T. brucei in Paul Voorheis' laboratory at Trinity College Dublin. Subsequently, I moved to Brussels in 1992, as an EMBO fellow, to join the group of Etienne Pays to study the expression and function of surface proteins in trypanosomes. In 1994 I was awarded a Marie Curie fellowship and focused on the problem of endocytosis in trypanosmes. Trypanosomes are absolutely dependent on their hosts for a supply of iron and lipoproteins and this traffic is highly polarized and extremely rapid in bloodstream forms of the parasite. In the summer of 2001 I was awarded a Senior Fellowship by the Trust to characterize proteins from the flagellar pocket and endocytic pathway in African trypanosomes. These parasitic protozoans cause sleeping sickness in humans and related diseases in domestic animals. Human sleeping sickness is invariably fatal unless treated. Of the four drugs currently employed to treat infections, resistance to two has emerged and the drug of choice, suramin, is suitable only in early stages. Trypanosomiasis is also considered one of the greatest health constraint to livestock productivity in sub-Saharan Africa with costs ranging between $2 and $5 billion annually. African trypanosomes are clearly a global health issue and are an enormous medical, veterinary and economic burden on some of the poorest regions on earth. Apart from their utilitarian interest, trypanosomes have proved to have great intrinsic scientific interest. These unicellular eukaryotes have evolved very differently from the better studied organisms, e.g. bacteria, yeast and metazoans, on which the foundations of biology have been built. Some of the most basic cellular and genetic pathways have developed very differently in trypanosomes but other processes first described and characterized in trypanosomes are now known to be important in mammalian cells. From the nucleus to the plasma membrane trypanosomes have provided fascinating insights including unusual genome organisation, pol I transcription of coding genes, expression sites and novel nuclear substructures, RNA editing, mitochondrial repression/activation, compartmentalization of glycolysis, GPI anchors, unusual organisation of surface proteins and the endocytic pathway, polarized cytoskeletons, golgi duplication and many other phenomena. By any criterion, whether biochemical, molecular or cellular, trypanosomes have more than punched their weight in terms of a contribution to our understanding of eukaryotic biology. osomes and returned to Trinity College Dublin at the end of 2001

  ACIDIC REPETITIVE PROTEIN   AFRICAN TRYPANOSOMES   BLOOD-STREAM FORMS   CELL-SURFACE   CONCANAVALIN-A   CROSS-LINKING   GPI-ANCHORED PROTEINS   LIPOPHILIC CATION   MEMBRANE-POTENTIAL CHANGES   MITOGENIC STIMULATION   NEURO-BLASTOMA   Parasitology   PH GRADIENTS   PHOSPHATIDYLINOSITOL MEMBRANE ANCHOR   PLASMA-MEMBRANE   PROCYCLIC FORMS   PROTON-MOTIVE FORCE   SACCHAROMYCES-CEREVISIAE   SECONDARY STRUCTURE   STREPTOCOCCUS-LACTIS   TRANSFERRIN RECEPTOR

. Expression and function of surface proteins in protozoan parasites. Endocytosis, protein traffic and flagellar pocket function.. Parasite Bioenergetics . regulation and function of actin cytoskeleton. . Molecular and cell biology of the African trypanosome Trypanosoma brucei. . Vesicular traffic and the actin cytoskeleton in T. brucei.