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Systematic exploration of peroxisomal structure and function

Descrizione del progetto

Fare luce sulle proteine dei perossisomi e relative funzioni

I perossisomi, organelli legati alla membrana presenti in tutte le cellule eucariotiche, contengono concentrazioni molto elevate di enzimi ossidativi e sono i principali siti di utilizzo dell’ossigeno. Svolgono un ruolo fondamentale nella differenziazione, nello sviluppo e nel metabolismo, pertanto un eventuale loro malfunzionamento potrebbe essere implicato in molte malattie. Comprendere meglio le loro proteine, le funzioni metaboliche e le relative dinamiche come unità cellulari farà progredire in modo significativo la capacità di caratterizzare, diagnosticare e trattare le malattie. Il progetto PeroxiSystem, finanziato dal Consiglio europeo della ricerca, utilizzerà strumenti ad alta tecnologia per scoprire nuove proteine dei perossisomi, mapparne le funzioni e determinare i meccanismi con cui i questi comunicano con altri organelli. Tali strumenti saranno facilmente applicabili ad altri organelli, accelerando una più ampia comprensione della biologia cellulare.

Obiettivo

Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. This key organelle propagates cellular signals for differentiation, development and metabolism, and thus it is no surprise that a large number of diseases, including metabolic disorders, have been linked to peroxisomal dysfunction. Despite the importance of peroxisomes many fundamental questions remain open. For example, we do not know the entire proteome of peroxisomes, the extent of their metabolic functions, how peroxisomes change to meet cellular requirements or how they interact and communicate with other cellular organelles. In this proposal we suggest to employ our expertise and unique toolsets, successfully applied in the study of whole organelles, to shed new light on peroxisomes as a cellular unit – a PeroxiSystem. We propose to combine state-of-the art high content tools with mechanistic studies to uncover new peroxisomal proteins under a variety of growth conditions (Aim1), map the functions of unstudied peroxisomal proteins using both systematic and hypothesis driven approaches (Aim 2) and unravel how peroxisomes communicate with other organelles (Aim 3). To perform these studies we will build on expertise attained during an ERC StG: combining high throughput genetic manipulations of yeast libraries alongside high content screens. Importantly, we will try to bridge the knowledge gap in peroxisomal biology by creating new tools that can be applied to this unique organelle. Our findings should make an important step towards an unprecedented, thorough and multifaceted understanding of peroxisomes, their cellular geography and roles as well as their regulation when presented with various metabolic conditions. More broadly, the approaches presented here can be easily applied to study any organelle of choice, thus providing a conceptual framework in the study of cell biology.

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Istituzione ospitante

WEIZMANN INSTITUTE OF SCIENCE
Contribution nette de l'UE
€ 2 000 000,00
Indirizzo
HERZL STREET 234
7610001 Rehovot
Israele

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 2 000 000,00

Beneficiari (1)