Innovating Works

SystemDirectMS

Financiado
A Native Mass Spectrometry Systemic View of Cellular Structural Biology
Protein structure and consequently function is influenced by the cellular content. The array of splice variants, post-translational modifications, cleavages and the ability to bind cofactors and drugs, is governed by the surroundi... Protein structure and consequently function is influenced by the cellular content. The array of splice variants, post-translational modifications, cleavages and the ability to bind cofactors and drugs, is governed by the surrounding cellular milieu. This is determined by internal and external cues such as cell type, developmental stage, stress conditions, disease and aging, which give rise to an ensemble of distinct protein entities. To study this diversity, there is a need for methods that enable structural studies under close-to-life conditions, maintaining the natural environment and biological diversity, features that are often lost during biochemical purifications. Our recent discovery that native MS can be conducted within crude cellular lysates (direct-MS), while preserving the biological context, offers many new experimental avenues for investigating protein interactions and diversity. Here, we propose to take native MS to a new dimension: enabling a systemic view of cellular structure biology by endorsing technological, computational and methodological developments. To do this we will: (i) Establish a platform for high-throughput screening of protein interactions. (ii) Unravel protein interactions in human and other eukaryotic cells; (iii) Develop a method for whole-organ direct-MS analysis, unravelling the tissue-specific proteoform landscape. Each of our three independent but complementary aims involves a different biological system, going from bacteria through human cells to intact tissues. Together, these advances, in conjunction with the high-resolution and sensitivity afforded by current mass spectrometers, has the potential to advance a plethora of fields, including cell biology, pharmacology and biotechnology. Overall, we anticipate this project will promote the integration of direct-MS into the cellular structural biology toolkit, providing valuable insights not attained by other structural biology methods or artificial intelligence algorithms. ver más
30/04/2028
3M€
Duración del proyecto: 60 meses Fecha Inicio: 2023-04-10
Fecha Fin: 2028-04-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-10
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2022-ADG: ERC ADVANCED GRANTS
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 3M€
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