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Lung tissue-like culture system for bacterial pathogens to support antibiotic drug discovery (Efficacy and PK)

Research Project
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01.01.2021
 - 31.12.2022

The focus of the Roche antibiotics discovery group is to identify broad-spectrum antibiotics with novel Mode of Action (MOA). A key indication is the treatment of Gram-negative, Difficult-to-treat (DTR), hospital-acquired infections;specifically, Hospital Acquired Pneumonia (HAP) / Ventilator Acquired Pneumonia (VAP), that are among the mostchallenging and life-threatening bacterial infections today and therefore, deserve a close attention (Petite andNguyen, 2018; Weiss. et al., 2019). In order to validate novel molecular entities identified in high throughput screens,Roche aim to establish an advanced cellular system that allows simulation of human lung infections, especiallyHAP/VAP. Epithelix, a Geneva based company, has engineered an in vivo-like 3D cell culture model, MucilAir, mimicking lung(bronchial) airway system. Infection of the MucilAir system with P. aeruginosa led to a loss of the "epithelial barrier"function of the lung epithelium as observed during in vivo infections (Bertinetti C. et al, poster from Epithelix). In this project, Roche propose to adapt the MucilAir system and establish infection conditions for other Gram-negative bacteria to be able to: assess potency and PK properties of prioritized hit series, enable selection of clinical candidates improve the translation of in vitro data to human infections, thereby reducing the use of animal models (3R principle). Similar interest for developing novel tools to support antibacterial discovery and development is a major goal of Biozentrum University of Basel and ETH Zurich within the frame of National Center of Competence in Research (NCCR) AntiResist. Specifically, Prof. Christoph Dehio together with two other Biozentrum professors, Dirk Bumann and Urs Jenal have been awarded research funding to better understand pathogen physiology and heterogeneity in infected patients and development of in vitro systems that mimic relevant aspects of patient tissues. This project will be funded by Roche Center of Excellence (CoE, Roche Pharma Sciences) as part of an umbrella initiative of lung models for infection diseases, immunology and safety. Such environment is an opportunity of crossfertilization for technical knowledge, as the above-mentioned 3D cell system could also be adapted to study viral lung infections, inflammatory processes of the lung and to address the safety aspects of the developmental compounds. Direct collaborative connection between Roche and the research groups at Biozentrum and ETH Zurich will help to learn first-hand what type of progress is made in the field, with the possibility to gain access to patient sample analysis data and to the top advanced technologies available within the AntiResist initiative.

Collaborations & Cooperations

2022 - Participation or Organization of Collaborations on a national level
Broz, Petr, Prof., University of Lausanne, Research cooperation
2022 - Participation or Organization of Collaborations on a national level
Hierlemann, Andreas, Prof., ETH Zürich, Research cooperation

Funding

Lung tissue-like culture system for bacterial pathogens to support antibiotic drug discovery (Efficacy and PK)

Industriegelder, Sonstige Forschungskooperationen (GrantsTool), 01.2021-12.2022 (24)
PI : Jenal, Urs.

Members (2)

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Urs Jenal

Principal Investigator
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Rusudan Okujava

Co-Investigator