OCISBOxford Centre for Integrative Systems BiologyUniversity of OxfordNew Biochemistry Building
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Oxford OX1 3QU

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Trypanosomes

Trypanosomes cause devastating disease in animals and man. They have intriguing molecular and cellular biology. They transcribe their genes in a polycistronic manner in the absence of promoters in front of each gene. Cell type regulation of gene expression is therefore a predominantly post-transcriptional process. In addition their cell biology is dominated by their flagellum and the motility it directs. The genome of these parasites is sequenced and well annotated. We are using a variety of system biology approaches to study both of these aspects of the trypanosome. In the former we are working with mathematicians and computer scientists to understand cryptic regulatory sequences on the non-coding regions of the gene that control mRNA stability and processing. The approaches here include a Bayesian segmentation analysis. In addition we are using ab-initio codon-biased analyses to predict relationships between protein level expression and the sequence of the gene.

In the work on the flagellum we are studying its structure using 3D electron tomography and other advanced microscopy techniques involving computational analysis. Global component analyses and protein-protein interactome approaches are being developed through the application of larger-scale MS proteomics and advanced bioinformatics. Clues to individual protein function are developed via predictions from both of the above projects. We then test these predictions using RNA interference mutants and 2D-DIGE /ITRAC comparative proteomics along with cell biology of the phenotype.

Associated Projects

Mathematical Approaches to Systems Biology Research - Alex Fletcher
Ab initio discovery of regulartory elements in trypanosomatid genomes by Bayesian Segmentation - Steve Kelly
Biological Dynamics and Time Series Analysis for Systems Biology - Max Little
Development of a quantitative image analysis platform for biological systems spanning multiple length and time scales - Boguslaw Obara
Computational Approaches to Systems Biology Research - James Osborne
Modelling Biological Networks - David Smith

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