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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.

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

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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