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Decoding the Impact of Nuclear Organization on the Hierarchical VSG Activation in African Trypanosomes

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.

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Topic(s)

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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-2025-PF

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Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution

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.

€ 202 125,12
Address
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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