Innovating Works

Ubl-Code

Financiado
Revealing the ubiquitin and ubiquitin like modification landscape in health and...
Post-translational modifications (PTMs) of proteins are a major tool that the cell uses to monitor events and initiate appropriate responses. While a protein is defined by its backbone of amino acid sequence, its function is often... Post-translational modifications (PTMs) of proteins are a major tool that the cell uses to monitor events and initiate appropriate responses. While a protein is defined by its backbone of amino acid sequence, its function is often determined by PTMs, which specify stability, activity, or cellular localization. Among PTMs, ubiquitin and ubiquitin-like (Ubl) modifications were shown to regulate a variety of fundamental cellular processes such as cell division and differentiation. Aberrations in these pathways have been implicated in the pathogenesis of cancer. Over the past decade high-throughput genomic and transcriptional analyses have profoundly broadened our understanding of the processes underlying cancer development and progression. Yet, proteomic analyses and the PTM landscape in cancer, remained relatively unexplored. Our goal is to decipher molecular mechanisms of Ubl regulation in cancer. We will utilize the PTM profiling technology that I developed and further develop it to allow for subsequent MS analysis. Together with cutting-edge genomic, imaging and proteomic technologies, we will analyze novel aspects of PTM regulation at the level of the enzymatic machinery, the substrates and the downstream cellular network. We will rely on ample in-vitro and in-vivo characterization of Ubl conjugation to:a. Elucidate the regulatory principles of substrate specificity and recognition. b. Understand signalling dynamics in the ubiquitin system. c. Reveal how aberrations in these pathways may lead to diseases such as cancer. Identifying both the Ubl modifying enzymes and the modified substrates will form the basis for deciphering the molecular pathways in which they operate in the cell and the principles of their dynamic regulation. Revealing the PTM regulatory code presents a unique opportunity for the development of novel therapeutics. More broadly, our approaches may provide a new paradigm for addressing other complex biological questions involving PTM regulation. ver más
31/10/2021
WEIZMANN
2M€
Duración del proyecto: 66 meses Fecha Inicio: 2016-04-26
Fecha Fin: 2021-10-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-10-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2015: ERC Starting Grant
Cerrada hace 9 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5