Opendata, web and dolomites

STrkB

The structural biology of TrkB-BDNF signalling

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 STrkB project word cloud

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

biophysical    synaptogenesis    structure    kinase    cells    imaging    activation    brain    neurotrophic    molecules    efficient    protein    functional    relate    molecular    region    microscopy    techniques    mechanism    damaged    mimetics    electron    structures    behave    determinants    multidisciplinary    transmission    trkb    cellular    signaling    vivo    receptor    neuronal    fluorescence    repair    membrane    collaborative    length    trigger    extracellular    bdnf    tested    tools    validate    ray    downstream    models    me    modulate    nanobodies    gained    single    stages    hypotheses    propagation    recovery    circuits    affinity    survival    regulated    mechanistic    players    crystallography    binding    full    circuit    modulation    unknown    cryo    mouse    plasticity    chemical    signal    live    subsequently    platform    generate    synaptic    mutagenesis    engineer    acts    physico    architecture    multiple    tropomyosin    screened    model    mode    particle    structural   

Project "STrkB" data sheet

The following table provides information about the project.

Coordinator
UNITED KINGDOM RESEARCH AND INNOVATION 

There are not information about this coordinator. Please contact Fabio for more information, thanks.

 Coordinator Country United Kingdom [UK]
 Project website https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/radu-aricescu/
 Total cost 183˙454 €
 EC max contribution 183˙454 € (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 2017-07-01   to  2019-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNITED KINGDOM RESEARCH AND INNOVATION UK (SWINDON) coordinator 183˙454.00
2    MEDICAL RESEARCH COUNCIL UK (SWINDON) coordinator 0.00
3    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) participant 0.00

Map

 Project objective

Neuronal circuit development involves multiple stages that are regulated by neurotrophic factors. One of the key players, the brain-derived neurotrophic factor (BDNF), is involved in the development and functional modulation of circuits by promoting neuronal survival, synaptogenesis, synaptic transmission and synaptic plasticity. BDNF acts by binding to the tropomyosin-related kinase receptor B (TrkB), a type-I membrane protein, to trigger downstream signaling. However, the molecular architecture of this complex and the mechanism of signal propagation across the membrane remain unknown The key aim of this project is to define in structural and mechanistic terms the steps leading to TrkB activation upon BDNF binding. I will use X-ray crystallography to determine the structure of the extracellular TrkB-BDNF complex, and validate this model by mutagenesis and biophysical techniques. Single particle cryo-electron microscopy will be used to solve the full-length TrkB-BDNF complex structure. To validate and relate these structures to signaling, structure-based hypotheses will be tested in live cells by fluorescence imaging. Furthermore, to exploit the structural information gained above, I will engineer BDNF molecules with improved physico-chemical properties as well as generate nanobodies against the TrkB extracellular region. These will be screened by biophysical, structural and cellular approaches to evaluate their (i) binding mode and affinity and (ii) ability of promote TrkB activation. Subsequently, collaborative studies in mouse models will test whether these molecules behave as efficient BDNF mimetics in vivo. This multidisciplinary approach will enable me to define determinants of the TrkB-BDNF complex formation, its activation mechanism, and to use this information towards providing a platform for the design of novel tools that target and modulate this crucial signaling pathway, to promote synaptic repair and functional recovery in damaged neuronal circuits.

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "STRKB" 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 "STRKB" are provided by the European Opendata Portal: CORDIS opendata.

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

MAREITA (2018)

Mapping Remediation in Italian Literature Beyond the Digital Revolution

Read More  

POSPORI (2019)

Polymer Optical Sensors for Prolonged Overseeing the Robustness of civil Infrastructures

Read More  

GRAHAM (2018)

Concepts of Graph Theory Applied to the Human Microbiome

Read More