Cell2Cell | What makes a successfull pathogen? Understanding the impact of cell-to-cell heterogeneity in chromatin structure on infection and adaptation

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/860675
Start date: 01-11-2019
End date: 30-04-2024
Total budget - Public funding: 3 832 859,30 Euro - 3 832 859,00 Euro
Cordis data

Original description

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.

Status

SIGNED

Call topic

MSCA-ITN-2019

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.1. Fostering new skills by means of excellent initial training of researchers
H2020-MSCA-ITN-2019
MSCA-ITN-2019