Opendata, web and dolomites

RHOMBOSMALPS

Enabling malaria rhomboid proteases as drug targets: usage of molecular cookie cutters to shape novel activity assays and inhibitors.

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 RHOMBOSMALPS project word cloud

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

therapeutic    impractical    species    environment    create    yielding    function    inhibitors    date    molecular    lipid    verify    agent    protein    game    hence    difficulties    techniques    model    rhomboid    candidates    rules    druggability    retain    inviability    chemical    mutants    causative    drug    genetic    expansion    directed    selective    cutter    membrane    detergent    changer    rhomboids    therapeutics    optimize    strategy    encapsulating    assays    serve    isolate    probes    styrene    proteins    discovery    pfroms    members    biological    detergents    shortcomings    eliminate    individual    unfortunately    stability    alternative    red    generation    play    cookie    invasion    attractive    nanodiscs    blood    leads    maleic    turn    human    enzyme    compounds    falciparum    sma    manipulation    eukaryotic    agents    cells    rendered    straightforward    exact    track    functions    purification    free    physiological    proteases    polymer    bottleneck    intramembrane    acid    potent    malaria   

Project "RHOMBOSMALPS" data sheet

The following table provides information about the project.

Coordinator
KATHOLIEKE UNIVERSITEIT LEUVEN 

Organization address
address: OUDE MARKT 13
city: LEUVEN
postcode: 3000
website: www.kuleuven.be

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 Belgium [BE]
 Project website http://www.verhelstlab.net/
 Total cost 160˙800 €
 EC max contribution 160˙800 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2019-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KATHOLIEKE UNIVERSITEIT LEUVEN BE (LEUVEN) coordinator 160˙800.00

Map

 Project objective

Rhomboid proteases from P. falciparum, the causative agent of malaria, play a role in invasion of human red blood cells. The exact role of the individual members is challenging to track, because of difficulties in genetic manipulation of the P.falciparum and the inviability of some loss-of-function mutants. Hence, a chemical strategy is an attractive alternative. Unfortunately, the study of these eukaryotic rhomboids (PfROMs) has rendered impractical to date.

The bottleneck is that the current purification techniques use detergents that eliminate the physiological membrane, yielding low enzyme stability and activity. In its turn, this rules out the use of activity assays and chemical probes to study their function. Encapsulating these proteins in their lipid environment will address these shortcomings. I will develop a detergent free purification method, based on a styrene maleic acid (SMA) polymer that functions as a “molecular cookie cutter”, creating SMA-lipid-protein nanodiscs, which retain their biological properties upon purification.

Using this “molecular cookie cutter” to create lipid nanodiscs, I will isolate PfROMs and develop activity assays in order to identify and optimize novel inhibitors. The most potent and selective candidates will be evaluated in a malaria invasion model to verify the druggability of malaria rhomboids. Furthermore, these novel compounds may serve as leads for a new generation of therapeutic agents.

The straightforward expansion of our approach to other intramembrane proteases may be the game-changer for drug discovery and future therapeutics directed against rhomboids from other species.

 Publications

year authors and title journal last update
List of publications.
2018 Marta Barniol-Xicota, Steven H. L. Verhelst
Stable and Functional Rhomboid Proteases in Lipid Nanodiscs by Using Diisobutylene/Maleic Acid Copolymers
published pages: 14557-14561, ISSN: 0002-7863, DOI: 10.1021/jacs.8b08441
Journal of the American Chemical Society 140/44 2020-03-03

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

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

Widow Spider Mating (2020)

Immature mating as a novel tactic of an invasive widow spider

Read More  

STOPATT (2020)

Stochastic pattern formation in biochemical systems

Read More  

TOPOCIRCUS (2019)

Simulations of Topological Phases in Superconducting Circuits

Read More