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switchDecoding

Financiado

Decoding the path to cellular variation within pathogen populations

Heterogeneity amongst isogenic cells is pervasive throughout biology. Recently developed single-cell omics approaches are beginning to systematically reveal the repertoire of functionally distinct cell subpopulations within metazo... ver más

31/03/2028

LMU MUENCHEN

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

LUDWIGMAXIMILIANSUNIVERSITAET MUENCHEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-04-19

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2021-COG: ERC CONSOLIDATOR GRANTS

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LMU MUENCHEN

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Duración del proyecto: 71 meses Fecha Inicio: 2022-04-19
Fecha Fin: 2028-03-31

Líder del proyecto

LUDWIGMAXIMILIANSUNIVERSITAET MUENCHEN

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Heterogeneity amongst isogenic cells is pervasive throughout biology. Recently developed single-cell omics approaches are beginning to systematically reveal the repertoire of functionally distinct cell subpopulations within metazoan tissues. Pathogens frequently encounter changing and often hostile environments. To adapt to these challenges unicellular pathogen populations also exhibit a large degree of cell-to-cell heterogeneity, which often affects the outcome of infections. Yet, despite the importance of this cell-to-cell variation, very little is known about the mechanisms that control the level of heterogeneity in pathogen populations or why some isogenic populations are more heterogeneous than others. The goal of switchDecoding is to unveil the path to cellular variation. To this end I will go beyond identifying and describing new subpopulations of cells and elucidate the molecular pathways that establish them and modulate the level of cellular heterogeneity. As a model I will study the mechanism responsible for creating heterogeneity in surface antigen expression in the unicellular parasite Trypanosoma brucei. Antigenic variation is a widely employed strategy by evolutionarily divergent pathogens to evade the host immune response. Using a multidisciplinary approach, I will develop and combine single-cell multi-omics, lineage tracing and CRISPR-Cas-based genome manipulation strategies to characterize the processes, pathways and molecules regulating antigen switching in T. brucei. A better understanding of the mechanisms affecting the level of heterogeneity within a pathogen population will enable us to better predict how pathogens adapt to environmental challenges, including those that lead to the emergence of drug resistance. In the future this knowledge will enable the development of novel intervention strategies: drugs that modulate cell-to-cell heterogeneity to facilitate the clearance of infections.

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