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H2020Doctoral network2017–2020

Train2Target · An integrated mulTidisciplinary appRoach towards a new generAtIon of aNtibiotics: Targeting function and cross-talk of bacterial Envelope proTein machineries

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-01-01 → 2020-12-31
EU contribution
€3,931,378
Participants
17
Scheme
MSCA-ITN-ETN

Lines connect the coordinator with its partners.

Results in brief

An integrated mulTidisciplinary appRoach towards a new generAtIon of aNtibiotics: Targeting function and cross-talk of bacterial Envelope proTein machineries

Antibiotics are essential tools in modern medicine. They are crucial for invasive surgery and treatments such as chemotherapy, moreover their use has reduced childhood mortality and increased life expectancy. However, the rapid increase of multidrug-resistant bacteria has reduced the arsenal clinically useful antibiotics, and the spectre of untreatable infections is becoming a reality. Antimicrobial resistance (AMR) has indeed been recently listed as one of the greatest threats to human health by the WHO. This scenario is especially alarming from Gram-negative bacteria which are also intrinsically resistant to many antibiotics due to their tripartite envelope structure and calls urgently for the development of novel antibacterial dugs. The Train2Target is a multisectoral consortium gathering experts from academia and industry with the purpose of providing innovative solutions for antimicrobial drug discovery. The Gram-negative bacterial envelope is an essential structure, a formidable barrier that is difficult for antimicrobial drugs to penetrate and a place where resistance mechanisms may develop. It is also a well validated target for antimicrobial discovery and therefore a structure where identify new weaknesses for drug targeting. In this context, the general objective of the Train2Target research programme is to dissect bacterial envelope biogenesis pathways to identify novel targets, to propose new leads and to train 15ESRs in all scientific and non-scientific aspects related to the drug discovery process. Specific objectives of the Train2Target project are the following: - Dissecting at the molecular level the function of the core machineries that assemble the different bacterial envelope layers ; - Investigating how the activities of envelope machineries are orchestrated and coordinated to ensure appropriate growth of the different envelope layers during bacterial cell cycle; - Developing innovative screening strategies/technologies to identify molecules inhibiting envelope biogenesis. - Providing ESRs with transferable skills (i.e. commercialization of research results, IP management, ethical issues in research, communications, project management) as indispensable tools in the drug discovery process

Data: CORDIS, © European Union

Project objective

Train2Target is a multidisciplinary European Training Network built to address the challenge of the discovery of alternative antimicrobials. Innovative strategies to deliver a next generation of drugs are urgently needed. The alarming threats and spread of multi-drug resistant bacteria is currently leaving clinicians with very limited options to combat infections especially those from Gram-negative pathogens. The Train 2Target research programme focuses on the assembly of the well-known bacterial cell envelope from a new perspective. Indeed it aims to inhibit novel targets in envelope biogenesis by altering the function and misbalancing the coordination of envelope assembly machines, which build and assemble the Gram-negative bacterial envelope. A wide variety of chemical classes and compounds sources will be screened using innovative biochemical, biophysical and genetic assays to identify valuable hit scaffolds to be optimized into druggable leads. The high quality and credibility of our consortium is ensured by a strong interdisciplinary academia-industry partnership to encompass different complementary expertise ranging from microbiology, bacterial genetics, biochemistry, cell imaging, structural biology, biophysics and chemical synthesis. Our 9 academic groups are all renowned leaders in the cell envelope biogenesis field, whereas the complementary 5 SMEs and 3 Industry partners are specialised in drug discovery and development of novel anti-infective drugs. This unique combination of scientific excellence and industrial know-how in drug discovery covers the entire process from the design to the implementation of innovative antibacterial strategies and lead identification.Train2Target also represents a unique research platform to train 15 Early Stage Researchers and equip them with the necessary scientific and transferable skills that will make them highly competitive for both top European research institutions and the pharma/biotech job market.

Original text from CORDIS.

Participants

  • UNIVERSITA DEGLI STUDI DI MILANO · MilanoCoordinatorItaly
  • ACCELOPMENT SCHWEIZ AG · ZurichSwitzerland
  • AICURIS ANTI-INFECTIVE CURES AG · WUPPERTALGermany
  • ANTABIO · LabegeFrance
  • BASILEA PHARMACEUTICA INTERNATIONAL AG · BASELSwitzerland
  • BIOVERSYS AG · BaselSwitzerland
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisFrance
  • DANMARKS TEKNISKE UNIVERSITET · Kongens LyngbyDenmark
  • NAICONS SRL · SaronnoItaly
  • THE UNIVERSITY OF BIRMINGHAM · BirminghamUnited Kingdom
  • UNION THERAPEUTICS AS · HELLERUPDenmark
  • UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II · NapoliItaly
  • UNIVERSITAT BASEL · BaselSwitzerland
  • UNIVERSITE CATHOLIQUE DE LOUVAIN · LOUVAIN LA NEUVEBelgium
  • UNIVERSITEIT VAN AMSTERDAM · AmsterdamNetherlands
  • UNIVERSITY OF NEWCASTLE UPON TYNE · Newcastle Upon TyneUnited Kingdom
  • ZOETIS INTERNATIONAL SERVICES SAS · PARISFrance

Links

Data: CORDIS, © European Union