Descrizione del progetto
Ricercare differenze nei grovigli dei filamenti di cromatina potrebbe rivelare la ricetta per il successo di un agente patogeno
La maggior parte dei patogeni è rappresentata da organismi monocellulari o, nel caso dei virus, da piccole particelle parassite costituite da acido nucleico e gusci proteici esterni. Una volta che sono riusciti a invadere i nostri corpi, alcuni di essi all’interno della stessa comunità hanno maggiore successo nello stabilire un’infezione rispetto ad altri. Ricerche approfondite hanno rivelato meccanismi globali di adattamento e sopravvivenza dei patogeni. Tuttavia, si sa poco sulle variazioni locali o sull’eterogeneità cellula-cellula all’interno della stessa popolazione microbica. Cell2Cell sta studiando tale eterogeneità a livello di cromatina, il DNA e le proteine istoniche attorno alle quali questo si avvolge per formare i cromosomi. Studi pionieristici aiuteranno a chiarire come la cromatina è organizzata nei patogeni e in che modo l’eterogeneità della cromatina potrebbe favorire la colonizzazione di successo da parte di determinate cellule, fornendo munizioni nella guerra contro invasori spesso mortali.
Obiettivo
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)Coordinatore
80539 MUNCHEN
Germania