Structural Biology of Exopolysaccharide Secretion in Bacterial Biofilms

Projektinformationen

BioMatrix

ID Finanzhilfevereinbarung: 757507

DOI 10.3030/757507

EK-Unterschriftsdatum 8 November 2017

Startdatum 1 August 2018

Enddatum 31 Mai 2024

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 499 901,00

EU-Beitrag € 1 499 901,00

Koordiniert durch

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Ziel

Bacterial biofilm formation is a paramount developmental process in both Gram-positive and Gram-negative species and in many pathogens has been associated with processes of horizontal gene transfer, antibiotic resistance development and pathogen persistence. Bacterial biofilms are collaborative sessile macrocolonies embedded in complex extracellular matrix that secures both mechanical resistance and a medium for intercellular exchange.

Biogenesis platforms for the secretion of biofilm matrix components - many of which controlled directly or indirectly by the intracellular second messenger c-di-GMP - are important determinants for biofilm formation and bacterial disease, and therefore present compelling targets for the development of novel therapeutics. During my Ph.D. and post-doctoral work I studied the structure and function of c-di-GMP-sensing protein factors controling extracellular matrix production by DNA-binding at the transcription initiation level or by inside-out signalling mechanisms at the cell envelope, as well as membrane exporters involved directly in downstream matrix component secretion.

Here, I propose to apply my expertise in microbiology, protein science and structural biology to study the structure and function of exopolysaccharide secretion systems in Gram-negative species. Using Pseudomonas aeruginosa, Vibrio spp. and Escherichia coli as model organisms, my team will aim to reveal the global architecture and individual building components of several expolysaccharide-producing protein megacomplexes. We will combine X-ray crystallography, biophysical and biochemical assays, electron microscopy and in cellulo functional studies to provide a comprehensive view of extracellular matrix production that spans the different resolution levels and presents molecular blueprints for the development of novel anti-infectives. Over the last year I have laid the foundation of these studies and have demonstrated the overall feasibility of the project.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › microbiology › bacteriology
• natural sciences › earth and related environmental sciences › geology › mineralogy › crystallography
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• natural sciences › physical sciences › optics › microscopy › electron microscopy
• natural sciences › biological sciences › molecular biology › structural biology

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-2017-STG - ERC Starting Grant

Aufforderung zur Vorschlagseinreichung

ERC-2017-STG

Finanzierungsplan

ERC-STG - Starting Grant

Gastgebende Einrichtung

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

• Netto-EU-Beitrag: € 1 499 901,00
• Adresse: RUE MICHEL ANGE 3 ; 75794 Paris ; Frankreich
• Region: Ile-de-France › Ile-de-France › Paris
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 499 901,00

Begünstigte (1)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

Frankreich

• Netto-EU-Beitrag: € 1 499 901,00
• Adresse: RUE MICHEL ANGE 3 ; 75794 Paris
• Region: Ile-de-France › Ile-de-France › Paris
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 499 901,00