Exploring Trypanosoma brucei's lipid biosynthesis for drug targets

The Biophysical Sciences Institute seminar: Exploring Trypanosoma brucei's lipid biosynthesis for drug targets, will be presented by Dr Terry Smith (St-Andrews). 

1pm, 19 April, Durham University, CG91, Chemistry Department.

Abstract:

There are currently no effective treatments against many of the debilitating and
 fatal diseases caused by insect-transmitted protozoan parasites such as
 Trypanosoma brucei (African sleeping sickness), Trypanosoma cruzi (Chagas's)
, Leshmania, Plasmodium (malaria) and Toxoplasma. The cell-surface's of these
 parasites are covered in glycosylphosphatidylinositol (GPI) anchors and related 
molecules. T. brucei biosynthesis of  GPI anchors are required for their
 abundant variant surface glycoprotein which protects them against the harsh 
environment of the bloodstream. GPI anchor biosynthesis is a
 proven genetic and chemical target for therapeutic drugs and relies upon several lipid and glycolipid metabolic pathways. We are finding significant exploitable differences between human and parasitic
 biosynthetic pathways and enzymes. Inhibitor studies and chemical
 synthesis followed by screening of focused compounds libraries for lead
 compounds will ultimately result in therapeutic drugs against these Third World
 diseases.

Our multi-disciplinary research approach involves:

(a) In vivo and in vitro biosynthetic studies, to investigate the parasites
 de novo synthesis of lipids and glycolipds.

(b) Bioinformatics, molecular biology and molecular parasitology are used to 
clone novel genes, allowing gene-knockout and/or RNAi approaches to genetically
validate them as drug targets.

(c) Biochemical phenotyping of these modified parasites using labelling methods,
quantification of metabolites and proteins, enzymatic assays, various mass spec
methods and lipidomic approaches to help us understand the parasite's 
responses.

(d) Recombinant expression and development of enzymatic assays, ultimately for
 high-throughput screening, in conjunction with the design and chemical
 synthesis of biosynthetic inhibitors as drug leads.

For more information please contact the event organiser Dr Paul Denny (p.w.denny@durham.ac.uk) or admin.bsi@dur.ac.uk.  

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