Molecular mechanisms mediating immune evasion in African trypanosomes (360G-Wellcome-212211_Z_18_Z)

£1,695,299

The African trypanosome Trypanosoma brucei is an extraordinarily effective extracellular pathogen. Key for its survival is a protective Variant Surface Glycoprotein (VSG) coat, which is expressed at an extraordinarily high level from a VSG gene located in an RNA polymerase I transcribed VSG expression site. Although an individual trypanosome has multiple bloodstream form expression sites, stringent mono-allelic exclusion ensures that only one is transcribed at a time. We would like to understand how this mono-allelic exclusion operates. We have generated T. brucei strains with disrupted mono-allelic exclusion, which dynamically switch between two different expression sites. What restriction has disappeared? T. brucei additionally contains metacyclic expression sites, which are mono-allelically expressed in the relevant life-cycle stage. How are these different types of expression sites controlled? We have recently made the striking discovery that blocking trans-splicing leads to an abrupt halt in transcription of the active VSG expression site. How does RNA processing feed back to control this unusual RNA polymerase I transcription unit? Last, we have discovered that VSG synthesis is sensed during the cell cycle, and blocking its synthesis triggers a precise pre-cytokinesis cell cycle arrest. How does this happen, and what stress responses are triggered?

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Grant Details

Amount Awarded 1695299
Applicant Surname Rudenko
Approval Committee Science Interview Panel
Award Date 2018-07-17T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Senior Research Fellowship Basic Renewal
Internal ID 212211/Z/18/Z
Lead Applicant Prof Gloria Rudenko
Partnership Value 1695299
Planned Dates: End Date 2023-03-31T00:00:00+00:00
Planned Dates: Start Date 2019-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Anne Dell