Project description
Innovative model for understanding antigen activation in tropical diseases
Antigenic variation is a strategy used by pathogens to evade host immune responses. Still, the mechanisms determining the order of antigen activation are unclear. In Trypanosoma brucei, a model for studying this phenomenon, double-stranded breaks (DSBs) in antigen genes (VSGs) trigger antigen switching. Supported by the Marie Skłodowska-Curie Actions programme, the VSG-repair project will test how DNA damage affects nuclear dynamics and influences the choice of DNA repair pathways, thereby shaping VSG activation. Utilising advanced techniques from the Siegel lab, it will combine microscopy with genome-wide mapping to analyse the impact of spatial proximity and sequence identity on repair outcomes. This project will provide a model for VSG repair and develop strategies to address neglected tropical diseases.
Objective
Antigenic variation is a widely employed strategy for evading host immune responses, and it relies on similar functional principles even in evolutionarily divergent pathogens. These principles include the mutually exclusive expression of antigens and the periodic, nonrandom switching of antigen expression during infection. Despite decades of research, the mechanisms governing the order of antigen activation remain unknown.
In Trypanosoma brucei, a model organism for studying antigenic variation, double-stranded breaks (DSBs) within antigen genes (VSGs) act as key triggers for antigen switching. VSG-repair tests the hypothesis that DNA damage reshapes nuclear dynamics in a manner that spatial proximity, together with sequence identity, biases DNA repair template choice and thereby determines the hierarchy of VSG activation.
Building on recent advances in the Siegel lab—and leveraging DSB-inducible switching lines, established gene tagging strategies, and on-site imaging and NGS facilities— VSG-repair combines high-resolution microscopy with genome-wide mapping of homology search and a quantitative integration framework to determine how 3D proximity, sequence identity, and chromatin context influence repair outcomes. Scientifically, this will yield a model of VSG repair and general principles for homology repair-centered, non-model systems. Technologically, it will deliver an adaptable screening strategy suitable for genome tagging or inducible perturbations. Societally, it will strengthen the knowledge needed to address neglected tropical diseases. I bring a strong background in chromatin biology in divergent parasites and, under Prof. Siegel’s supervision, I will acquire complementary expertise in advanced microscopy, single-cell omics, and large-scale screening workflows. This training will equip me with the skills to transition to independence and establish myself as a group leader in chromatin regulation and cellular decision-making in parasitology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences health sciences parasitology
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics genomes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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)
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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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(opens in new window) HORIZON-MSCA-2025-PF
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80539 Planegg
Germany
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