Descripción del proyecto
La detección de diferencias en la cromatina enredada puede revelar la receta del éxito de un patógeno
La mayoría de los patógenos son organismos unicelulares o, en el caso de los virus, pequeñas partículas parasitarias formadas por ácido nucleico y envolturas proteicas externas. Una vez que han invadido con éxito nuestros cuerpos, algunos de una misma comunidad tienen un mayor éxito que los demás a la hora de producir una infección. Las amplias investigaciones realizadas han revelado los mecanismos globales de la adaptación y supervivencia de los patógenos. Sin embargo, apenas se dispone de información sobre las variaciones locales o la heterogeneidad entre las células de la misma población microbiana. Cell2Cell está estudiando esta heterogeneidad a nivel de la cromatina, el ADN y las proteínas histonas que dan forma a los cromosomas. Los innovadores estudios ayudarán a establecer cómo se organiza la cromatina de los patógenos y cómo su heterogeneidad podría favorecer el éxito de la colonización por parte de determinadas células, lo cual podría ser de gran utilidad en la lucha contra invasores a menudo letales.
Objetivo
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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MSCA-ITN - Marie Skłodowska-Curie Innovative Training Networks (ITN)Coordinador
80539 MUNCHEN
Alemania