Projet Cell2Cell (Horizon 2020, appel à projets 2019)
Action : Doctoral Networks
Panel : Life Sciences
Statut du projet : SIGNED

Infectious diseases kill millions of people worldwide every year. Decades of research have revealed important insights into the molecular mechanisms pathogens employ to establish lasting infections, yet little is known about what renders individual pathogens within a microbial population more successful at establishing an infection than others. Recent advances in single-cell technologies have started to revolutionize modern biology, unveiling an enormous degree of cell-to-cell heterogeneity. Often, phenotypic variability is not caused by genetic changes in the DNA sequence, but by epigenetic changes in the structural organization of DNA called chromatin. In multicellular organisms, this epigenetic plasticity plays a key role in developmental processes and cancer. In unicellular pathogens, cell-to-cell heterogeneity is hypothesized to promote the establishment of infections by allowing the pathogen to adapt to changing environments or evade the host immune response. To decrease the burden of infectious diseases, it is therefore, necessary to better understand how infections are enabled by cellular heterogeneity at the chromatin level of the pathogen. Several limitations have previously challenged this endeavor, including small genome size (i.e. low signal-to-noise) and the lack of knowledge of how chromatin is organized in pathogens. Cell2Cell proposes to overcome these barriers by bringing together (1) experts in pathogen biology; (2) the use of unicellular yeast species to serve as chromatin models; (3) single-cell technologies; (4) bioinformatics tools. Using state of the art technologies, we will train early stage researchers to identify the molecular mechanisms that control cell-to-cell heterogeneity in pathogens. The proposed research will contribute to the elucidation of how heterogeneity affects the outcome of diseases and give rise to highly skilled scientists that are well prepared to face the demands of modern genomics research in academia and industry.

Mots clés : single cell, pathogens, protozoan parasites, yeast, heterogeneity, chromatin, gene expression, molecular biology, next generation sequencing

Participants :
- Epigenetiks genetik biyoinformatik yazilim as (Turquie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 235248.12 €
- University of Giessen (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 256299.35 €
- Weizmann Institute of Science (Israël) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 263500.92 €
- Ludwig-Maximilians-Universität München (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 754854.25 €
- Helmholtz Zentrum München (Allemagne) — Partner, beneficiary, Recherche, subvention : 505576.8 €
- University of Oxford (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 303172.56 €
- Swiss Tropical and Public Health Institute (Suisse) — Partner, beneficiary, Recherche, subvention : 281276.64 €
- Institut Curie (France) — Partner, beneficiary, Recherche, subvention : 274802.04 €
- Radboud University Nijmegen (Pays-Bas) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 265619.88 €
- University of Lisbon (Portugal) — Partner, beneficiary, Recherche, subvention : 237720.24 €
- Karolinska Institutet (Suède) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 281982.96 €
- Cellsorter muszaki kutato es fejleszto kft (Hongrie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 229715.28 €