ICREA research professor Carme Rovira, awarded in the ERC 2020 Synergy Grants call

La professora d'investigació ICREA al Departament de Química Inorgànica i Orgànica i membre de l'Institut de Química Teòrica i Computacional de la UB.
La professora d'investigació ICREA al Departament de Química Inorgànica i Orgànica i membre de l'Institut de Química Teòrica i Computacional de la UB.
Research
(05/11/2020)

Carme Rovira, ICREA research professor, has been awarded a Synergy Grant from the European Research Council (ERC). Rovira, from the Department of Inorganic and Organic Chemistry of the UB, has received this award along with Gideon Davies, from the University of York (United Kingdom) and Hermen Overkleeft, from the University of Leiden (the Netherlands). This grant provides a funding of 9.1 million euros for the research carried out by these researchers in the field of enzymes that work on glycans (complex sugars) with major ramifications on human health and for a sustainable society.

 

La professora d'investigació ICREA al Departament de Química Inorgànica i Orgànica i membre de l'Institut de Química Teòrica i Computacional de la UB.
La professora d'investigació ICREA al Departament de Química Inorgànica i Orgànica i membre de l'Institut de Química Teòrica i Computacional de la UB.
Research
05/11/2020

Carme Rovira, ICREA research professor, has been awarded a Synergy Grant from the European Research Council (ERC). Rovira, from the Department of Inorganic and Organic Chemistry of the UB, has received this award along with Gideon Davies, from the University of York (United Kingdom) and Hermen Overkleeft, from the University of Leiden (the Netherlands). This grant provides a funding of 9.1 million euros for the research carried out by these researchers in the field of enzymes that work on glycans (complex sugars) with major ramifications on human health and for a sustainable society.

 

Today, the European Research Council  announced the results of the 2020 Synergy Grants call. These grants are amongst the most prestigious European grants for curiosity-driven research and are only awarded to teams of world-class researchers coming together to tackle major scientific challenges.

Named Carbocentre, the synergy team formed by Rovira, Davies and Overkleeft, and coordinated by the latter, will develop novel chemical entities termed “activity-based probes” (ABPs)  to study the enzymes involved in the synthesis and breakdown of carbohydrates. They will design compounds that inhibit and visualize each of the glycoprocessing enzymes, and apply them in the areas of biomedicine and biotechnology.

Carbohydrates (glycans), the most abundant and diverse class of biomolecules on Earth, have mind-boggling chemical diversity.  The team will develop chemistries to visualize, modulate and understand the enzymes involved in the synthesis, modification and breakdown of glycans with enormous great potential for human health and sustainable industries.

Their collaborative and synergistic approach of the researchers aims to harness computational and structural analyses of how enzymes (natureʼs catalysts) work and use that to inform chemical synthesis of activity-based probes that allow the detection, imaging and isolation of these enzymes in living systems.

Carme Rovira, also researcher at the Institute of Theoretical and Computational Chemistry of the UB (IQTCUB) and who will lead the computational strand, notes that  “it is a great honour to obtain this European funding, especially at this time. The three teams have incredible synergy. It will be wonderful to see how computation, structure and organic chemistry can come together for major biological insight ”.

Many viruses, including those causing  influenza and COVID-19, use glycans as part of their structure in order to enter the cell.  Many human diseases related to carbohydrate chemistry and our renewable energy portfolio is predicted to include biofuels as part of our sustainable portfolio. This ERC Synergy grant will enable groups in Barcelona, Leiden and York to tackle these major societal challenges.  


About Activity-based probes
Activity-based probes (ABPs) for glycoprocessing enzymes are small sugar-like molecules that act by reacting within enzyme active sites as if they were substrates, only to remain covalently and irreversibly bound. The nature of the ABP structure informs on the substrate preference of the tagged enzyme, even if other (structural, genetic) information is lacking.

ABPs can be used to diagnose tissue from patients suffering from one of the several rare diseases associated to glycoprocessing enzymes (for instance in Gaucher disease, a glycogen storage disorder in which lysosomal β-glucosidase is absent).

Competitive inhibitors can also be designed inspired on the structure of covalent ones for application in the biomedical domain. Activity-based probes can equally be applied in biotechnology, to dissect the complex secreted enzyme repertoire of biomass-degrading fungi and bacteria, boosting the discovery of new enzymes for biofuel production.

 

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Molecular mechanism of action of a glycoprocessing enzyme (in particular, an enzyme catalyzing the formation of a new glycan) obtained from computational chemistry. The dissection of the molecular mechanism will allow us to design selective activity-based probes for each enzyme. Image: Beatriz Piniello/UB