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Tension of ENDOmembranes maintained by TORC1

Total Cost €


EC-Contrib. €






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

Project "TENDO" data sheet

The following table provides information about the project.


Organization address
city: GENEVE
postcode: 1211

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


Take a look of project's partnership.

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


 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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