Current Research

Section I. How do trypanosomes 'listen' to each other to enable their developmental progression to stumpy forms in the bloodstream

When trypanosomes proliferate in the bloodstream they release a soluble signal, termed Stumpy Induction Factor (SIF). SIF causes cell-cycle arrest, differentiation and the acquisition of differentiation competence characteristic of stumpy forms. Although SIF has remained elusive, we have been successful in identifying the molecules that transduce the SIF signal within the parasite to drive stumpy formation. This exploited a genome-wide RNAi library screen whereby parasites that were unable to respond to the SIF signal could be selected based on their continued ability to proliferate (in fact, a SIF mimic was used to allow the screen to be carried out in the laboratory-adapted cell lines routinely used in trypanosome genome-wide screens). This screen identified a cohort of molecules (~30) that contribute to physiological stumpy formation, including signal transduction components (kinases, phosphatases) as well as gene expression regulators. A major part of our research focus at present is to understand how this pathway operates and how the components interact. This is providing the most detailed analysis of environmental sensing and cell-cell communication in these parasites. This has significant relevance more broadly also, since other major parasites also exhibit cell-cell communication including Plasmodium, the parasites that cause malaria.

 

screen for SIF signalling components

Selection regimen for the isolation of SIF pathway components

SIF signalling pathway

Predicted order of SIF pathway components.

 

For more information on this section, refer to

Binny M. Mony*; Paula MacGregor*; Alasdair Ivens, Federico Rojas, Andrew Cowton, Julie Young, David Horn and Keith R. Matthews (2013)

Genome wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei

Nature doi:10.1038/nature12864

Pollit, L.C.; MacGregor, P.; Matthews, K. R. and Reece, S.

Malaria and trypanosome transmission: different parasites, same rules?
Trends in Parasitology, Feb 21. [Epub ahead of print]

 

 

 

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