Project description
Teasing out differences in tangled chromatin may reveal a pathogen's recipe for success
Most pathogens are single-celled organisms, or in the case of viruses, small parasitic particles consisting of nucleic acid and outer protein shells. Once they have successfully invaded our bodies, some within the same community are more successful at establishing infection than others. Extensive research has revealed global mechanisms for pathogen adaptation and survival. However, little is known about local variations or cell-to-cell heterogeneity within the same microbial population. Cell2Cell is studying that heterogeneity at the level of chromatin, the DNA and histone proteins its wound around that make up chromosomes. Ground-breaking studies will help elucidate how chromatin is organised in pathogens and how chromatin heterogeneity might favour successful colonisation by certain cells, providing ammunition in the war against often-deadly invaders.
Objective
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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Coordinator
80539 MUNCHEN
Germany