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

Total Cost €


EC-Contrib. €






 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.

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

Project "RHOMBOSMALPS" data sheet

The following table provides information about the project.


Organization address
address: OUDE MARKT 13
city: LEUVEN
postcode: 3000

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
 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


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 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.


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

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