Objective
Pathogens use antigenic variation to evade host antibodies and cause diseases in humans. Interestingly, in many species antigen switching occurs non-randomly in a hierarchical manner, with specific antigen genes selected in succession. Trypanosoma brucei is a key model organism for the study of antigenic variation in which antigen switching hierarchies of its Variant Surface Glycoprotein (VSG) genes operate. However, how exactly this hierarchy is determined is unknown. Studies in T. brucei have indicated that the spatial positioning of VSG genes within the nucleus is important for controlling their activation. However, to date no systematic investigation of VSG gene nuclear positioning and antigen switching hierarchies has been performed.
In this project, I would test the hypothesis that antigen switching hierarchies in trypanosomes are mediated by the spatial positioning of VSG genes in the nucleus. Using T. brucei cell lines in which different antigen switching pathways can be induced, I will determine whether silent VSGs in close spatial proximity to the active VSG before switch induction are selected next in the antigen switching pathway. This will be investigated by integrating a combination of Micro-C to monitor VSG nuclear positioning before and after switching followed by scRNA-seq. I will also develop a dCas9 artificial tethering system to tether silent VSGs either towards or away from the active VSG before switch induction to create a synthetic VSG switching hierarchy.
These experiments will generate important insights into the mechanisms which control antigen switching and provide valuable tools for studying nuclear organisation in kinetoplastid parasites.
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2022-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
80539 Planegg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.