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Deciphering SENsing Of membrane satuRation with functional genetics SENSOR

All living cells must control the biophysical properties of their lipid membranes. Accordingly, dysregulation of the mechanisms underlying this process is associated with a wide range of human diseases, including amongst others me... see more

31/08/2023

Academisch Medisch...

176K€

Project Budget: 176K€

Project leader

Academisch Medisch Centrum AMC No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

Financing granted El organismo H2020 notifico la concesión del proyecto The day 2023-08-31

MSCA-IF-2020: Individual Fellowships Objective:The goal of the Individual Fellowships is to enhance the creative and innovative potential...

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Cerrada does 5 years

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characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

Private Information

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1 Participantes

Academisch Medisch Centrum A...

175.57K€ | Leader

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Project duration: 28 months Date Start: 2021-04-02
End date: 2023-08-31

Project leader

Academisch Medisch Centrum AMC No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 176K€

participation deadline Sin fecha límite de participación.

Project description All living cells must control the biophysical properties of their lipid membranes. Accordingly, dysregulation of the mechanisms underlying this process is associated with a wide range of human diseases, including amongst others metabolic disorders and cancer. In recent years, the role of fatty acid (FA) saturation in controlling membrane fluidity has gained great attention given the realization that the balance between unsaturated fatty acids (UFAs) and saturated fatty acids (SFAs) in the membrane is dynamic, and can be regulated to meet cellular needs. Herein, the SREBP-1 and -2 transcription factors play a pivotal role owing to their ability to control the level of cholesterol and fatty acid saturation. Our ability to understand the regulation of membrane fluidity and the intimate interaction between this property and SREBP regulation is hampered by the lack of experimental methods to faithfully follow FA saturation in a tempo-spatial resolution in live cells. To address this gap and to advance the field beyond the current state-of-the-art I therefore propose to combine my expertise in advanced functional genetic approaches with that of Prof. Zelcer in the molecular regulation of lipid metabolism, and specifically aim to: 1) Establish a universal and widely-applicable cellular system that reports on ER membrane saturation in mammalian cells through the use of an innovative fluorescent-based reporter. 2) Determine the genetic traits that govern ER membrane saturation in an unbiased manner with state-of-the-art genome-wide CRISPR/Cas9-based assays. The proposed experiments will greatly enhance our understanding of the regulation of FA metabolism and will result in the generation of innovative and widely applicable experimental tools for in vitro and in vivo monitoring of membrane saturation. These studies may also inform on novel therapeutic strategies to treat lipid-associated disorders.

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