Project description
Shedding light on peroxisomal proteins and their functions
Peroxisomes are membrane-bound organelles found in all eukaryotic cells. They contain very high concentrations of oxidative enzymes and are major sites of oxygen utilisation. They play a critical role in differentiation, development and metabolism, making their dysfunction implicated in many diseases. Enhancing understanding of their proteins, metabolic functions and dynamics as cellular units will significantly advance our ability to characterise, diagnose and treat disease. The European Research Council-funded PeroxiSystem project will use high-tech tools to discover new peroxisomal proteins, map their functions and determine the mechanisms by which peroxisomes communicate with other organelles. These tools will be easily applicable to other organelles, accelerating a broader understanding of cell biology.
Objective
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.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural scienceschemical scienceselectrochemistryelectrolysis
- natural sciencesbiological sciencescell biology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesorganic chemistryamines
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
7610001 Rehovot
Israel