Innovating Works

HighResCells

Financiado
A synergistic approach toward understanding receptor signaling in the cell at ve...
A synergistic approach toward understanding receptor signaling in the cell at very high resolution Members of the Epidermal Growth Factors Receptor family (EGFRs) influence cell growth and proliferation, and are pivotal in all phases of tumor progression. We will use this receptor family as an example with which to develop a gr... Members of the Epidermal Growth Factors Receptor family (EGFRs) influence cell growth and proliferation, and are pivotal in all phases of tumor progression. We will use this receptor family as an example with which to develop a ground-breaking new technology to study cellular signaling towards atomic resolution, in situ. Therefore, we propose to employ an interdisciplinary approach for studying EGFR family of receptors, where we follow their conformational and oligomeric states as well as bound ligands and signal transduction molecules during different activation states at atomic resolution in situ. We will progress from engineered to native receptor forms, and from defined membrane vesicles to whole cells, and employ 3D structure analysis by cryo-electron tomography, greatly enhanced by novel image processing approaches, mass spectroscopy definitions of receptor modifications and interaction partners, as well as advanced protein engineering to identify, orient and freeze receptors for this method development. This collaborative project addresses the properties of the EGFR family across a wide range of complexity and dimensions, in the cellular environment, through their high-resolution structures and changes during receptor recycling. This collaborative network, addressing EGFR from complementary angles, is most likely to generate substantial new information on these assemblies and to yield a deep understanding of the mechanisms underlying their structure and function. The EGFR family has been the focus of many tumor therapies, with the aim of intercepting their signaling, and this project will contribute to a more detailed understanding of their mode of action and thus the more rational development of such therapies in the future. However, the technology that will be developed will be generally applicable and may thus help to contribute to a paradigm change for structural biology, enabling atomic resolution description of receptors in their cellular environment. ver más
30/11/2024
UZH
8M€
Duración del proyecto: 70 meses Fecha Inicio: 2019-01-24
Fecha Fin: 2024-11-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2019-01-24
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2018-SyG: ERC Synergy Grant
Cerrada hace 7 años
Presupuesto El presupuesto total del proyecto asciende a 8M€
Líder del proyecto
UNIVERSITAT ZURICH No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5