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TENDO SIGNED

Tension of ENDOmembranes maintained by TORC1

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 TENDO project word cloud

Explore the words cloud of the TENDO project. It provides you a very rough idea of what is the project "TENDO" about.

vice    dissipates    medically    depletion    reveal    vacuolar    insensitive    confirmed    inactive    central    vitro    made    membrane    domain    create    details    huge    toroid    helix    senses    discovery    compound    inhibited    bacterial    imaging    inform    revealed    forms    coupling    signalling    transferable    functions    suite    molecules    mechanotransduction    inhibitor    screens    kinase    regarding    assembly    assembles    biosensor    protein    tension    yeast    pm    assays    solving    versa    bound    therapeutic    learned    interventions    homeostasis    torc1    human    variant    nutrient    regulates    torc2    storm    enabled    tools    vm    named    tor    frap    glucose    phosphoproteomics    chemical    plays    serves    structure    em    throughput    genetic    lack    mechanisms    conserved    synthesis    regulation    cryo    ser    biology    cues    biomass    prompted    probes    grant    small    ask    regulated    thr    macrolide    rapamycin    plasma    concurrently    sensitive    quantitative    monitor    overcame    turnover    complexes    lessons   

Project "TENDO" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE GENEVE 

Organization address
address: RUE DU GENERAL DUFOUR 24
city: GENEVE
postcode: 1211
website: www.unige.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙257˙546 €
 EC max contribution 2˙257˙546 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-ADG
 Funding Scheme ERC-ADG
 Starting year 2019
 Duration (year-month-day) from 2019-05-01   to  2024-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE GENEVE CH (GENEVE) coordinator 2˙257˙546.00

Map

 Project objective

The target of the bacterial macrolide rapamycin, TOR, is a ser/thr protein kinase that assembles into two distinct protein complexes, conserved from yeast to human, we named TORC1 and TORC2. TORC1 is directly bound and inhibited by rapamycin and studies with rapamycin have revealed that TORC1 plays a central role in coupling nutrient cues to biomass synthesis and turnover. The lack of a specific inhibitor for TORC2 has made the study of this complex much more challenging. We overcame this challenge by solving the structure of yeast TORC2 which revealed why it is insensitive to rapamycin and enabled us to create a rapamycin-sensitive TORC2 variant. We also developed two small molecules, one that dissipates plasma membrane (PM) tension and the other that serves as a biosensor of PM tension. With this suite of chemical-biology tools we confirmed that TORC2 functions in a mechanotransduction pathway to maintain tension homeostasis of the PM. Concurrently, solving the structure of TORC1 revealed that its activity is regulated via assembly into a huge, inactive helix which we named a TOROID – TORC1 Organized in an Inactive Domain. In this grant, was ask if these major advances are transferable; i.e. can lessons learned regarding TORC2 be applied to TORC1, and vice versa? Our major aim is to determine if and how TORC1 regulates vacuolar membrane (VM) tension. To this end, we will develop novel chemical probes to monitor VM tension and we will use genetic screens, quantitative phosphoproteomics, in vitro assays, high-throughput compound screens, STORM and FRAP imaging, and state-of-the-art cryo-EM to learn how TORC1 senses and regulates VM tension. Our other aim, prompted by our TOROID discovery, is to solve the TOROID-like structure that TORC2 forms upon glucose depletion. This work will reveal new mechanisms in growth control, and details in TORC1 and TORC2 regulation that may inform future therapeutic interventions for these medically relevant signalling complexes.

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lastchecktime (2021-05-06 10:40:33) correctly updated