Opendata, web and dolomites

MARS SIGNED

Mechanism of allosteric regulation of SHP2 phosphatase and its role in cancer and geneticdiseases: a multidisciplinary computational, structural and biological approach

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 MARS project word cloud

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

peptidomimetic    regulatory    leukemia    domains    protein    er    basal    terminal    of    molecular    tumors    causes    50    hematologic    domain    whereas    allosteric    disease    dissociation    architecture    mechanisms    compounds    inhibitors    combined    coupled    external    mapk    xs    juvenile    expert    computational    dissect    src    site    diseases    shows    class    ptp    events    containing    md    deeper    ray    phosphopeptide    consolidated    gene    individuals    italian    somatic    signaling    hi    shp2    activation    dynamic    encoding    inhibit    pp    active    atomic    functional    inactive    dynamics    specialist    molecules    30    jmml    transition    ras    expertise    treat    dysregulation    structure    mutations    mechanism    sh2    homology    complemented    ptpn11    implicated    combination    scattering    syndrome    assays    germline    researcher    multidomain    ligand    myelomonocytic    rarely    noonan    biology    goals    phosphatase    guaranteed    binding    malignancies    function    regulation    favoring    host    tyrosine    human    found    biochemical    blocks    compatible    perturb   

Project "MARS" data sheet

The following table provides information about the project.

Coordinator
GEORG-AUGUST-UNIVERSITAT GOTTINGENSTIFTUNG OFFENTLICHEN RECHTS 

Organization address
address: WILHELMSPLATZ 1
city: GOTTINGEN
postcode: 37073
website: http://www.uni-goettingen.de

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 Germany [DE]
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2019-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    GEORG-AUGUST-UNIVERSITAT GOTTINGENSTIFTUNG OFFENTLICHEN RECHTS DE (GOTTINGEN) coordinator 159˙460.00

Map

 Project objective

SHP2 is an SH2 domain-containing protein tyrosine phosphatase with a key role in the RAS-MAPK signaling pathway. Germline mutations in PTPN11, the gene encoding SHP2, occur in 50% of individuals affected by Noonan syndrome, whereas somatic mutations in this gene cause more than 30% of cases of juvenile myelomonocytic leukemia (JMML), and are more rarely found in other hematologic malignancies and tumors. The X-ray structure of SHP2 shows a multidomain architecture compatible with an allosteric regulatory mechanism: under basal conditions SHP2 is inactive, because its N-terminal Src homology 2 (N-SH2) domain blocks the active site of the protein tyrosine phosphatase (PTP) domain. Binding of the N-SH2 domain to a phosphopeptide (PP) ligand causes SHP2 activation by favoring dissociation of the N-SH2 and PTP domains. To characterize this dynamic transition at the atomic level, will be used a combination of state of the art computational methods coupled to X-ray scattering (XS) and biochemical assays. Major goals of the proposed studies are to explain how disease-associated mutations perturb the regulatory events controlling SHP2 function, and design new molecules able to inhibit SHP2 binding to signaling partners. The project implementation is guaranteed by the expertise of the Experienced Researcher (ER) in molecular dynamics (MD) studies of allosteric mechanisms that is complemented by the consolidated expertise of the host institution (HI) in the combined use of MD and XS, together with the external collaboration of an Italian expert in SHP2 biology and a US specialist in XS. Overall, the proposed research will provide a deeper understanding of SHP2 regulation, and dissect the molecular mechanisms implicated in its functional dysregulation in human disease. The planned studies are expected to provide a new class of lead compounds to treat SHP2-associated diseases. Finally, a new computational approach for the design of peptidomimetic inhibitors will be developed.

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "MARS" project.

For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.

Send me an  email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.

Thanks. And then put a link of this page into your project's website.

The information about "MARS" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.3.2.)

lanloss (2020)

Landscapes of Loss: Mapping the Affective Experience of Deforestation Among Diverse Social Groups in the South American Chaco

Read More  

MingleIFT (2020)

Multi-color and single-molecule fluorescence imaging of intraflagellar transport in the phasmid chemosensory cilia of C. Elegans

Read More  

MathematicsAnalogies (2019)

Mathematics Analogies

Read More