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Training European Experts in Inflammation: from the molecular players to animal models and the bedside

Periodic Reporting for period 2 - INFLANET (Training European Experts in Inflammation: from the molecular players to animal models and the bedside)

Okres sprawozdawczy: 2023-03-01 do 2025-05-31

The high prevalence of chronic inflammatory diseases has major impacts on life quality and healthcare costs in western societies. Accelerating the pace of anti-inflammatory drug discovery is a formidable challenge. This requires a comprehensive understanding of inflammatory processes, allowing us to link the underlying genetic, molecular and cellular events to the physiological processes in inflamed tissues.
The goal of INFLANET is to:
(1) Understand how inflammatory signals are detected, integrated and propagated in an organism.
(2) Elucidate the genetic bases of inflammatory disorders and inform therapeutic strategies.
(3) Use cutting-edge intravital imaging strategies in animal models to study inflammatory processes, and anti-inflammatory drugs actions.
(4) Develop original mathematical modelling tools to analyse the wealth of data generated, to inform disease model development, and to provide tools for physicians to understand the pathological basis of inflammatory disorders.
An enthusiastic group of fifteen Marie Curie Research Fellows have been recruited between 2021 and 2023. During the 51 months of the project from 2021 to 2025, they have been trained through research, PhD enrolment in their respective institutions and via 5 central network-wide training events with physical presence and digital conferences. They addressed critical issues related to inflammation by developing complex models, identifying novel anti-inflammatory drugs and therapeutic targets, and effectively communicating their findings to a broad audience.
We purified novel danger signals released upon injury, which play a key role in triggering inflammatory responses. We determined the structure of these signals along with that of their receptors to better understand their interactions and explore how small molecules could be used to disrupt their binding. Additionally, we investigated their expression in animal models during episodes of inflammation.
We also explored how the SARS-CoV-2 spike protein may contribute to cytokine storm development, and how bacteria related to tuberculosis can induce inflammation.
To visualize inflammatory processes in living organisms, we developed new fluorescent tools and innovative imaging strategies, enabling us to observe how inflammatory episodes are initiated and propagated throughout the body. We further implemented computational algorithms and developed mathematical models to reconstruct the attractant fields that guide leukocyte migration during inflammation.
Moreover, we applied transcriptomic approaches—ranging from single-cell analysis to whole tissue profiling—to gain deeper insights into the molecular networks driving immune cell responses.
By analyzing patient data, we identified a novel human mutation responsible for a familial inflammatory disease. This discovery paves the way for the development of new therapeutic strategies targeting such conditions.
Building on our original findings, we have also developed new approaches for screening potential drugs to treat inflammatory diseases.
Numerous biological tools, software applications, and experimental protocols developed within the framework of the INFLANET project were shared across the consortium. These resources are regularly published and made available for use by external developers and scientific community. All scientific publications and related datasets are available in open access. Project results were presented at numerous national and international conferences throughout the duration of the project, with particular emphasis during our final dissemination meeting held in 2024 in Visegrád, Hungary.
The aim of our efforts is to validate new strategies to discover new anti-inflammatory drugs. We have now validated the biological models and the screening strategies to do so, and are confident that our results will help identifying novel anti-inflammatory drugs and therapeutic targets to treat inflammatory diseases.
In terms of medical image analysis, new tools and new work flows are now available to study laboratory data and to draw conclusions from screens to discover new drugs. These resources are open access and therefore available for use by external developers.
Thanks to the effective integration of hands-on training, the central INFLANET training program, and the complementary training provided by the ESRs’ respective doctoral schools, the project made a significant contribution to structuring doctoral training at the European level and enhancing career prospects for INFLANET researchers.
To raise public awareness and support the dissemination of our results, we produced a series of educational videos available on our YouTube channel, as well as MOOCs and a serious game—designed for smartphones—to help teenagers learn about the immune system and inflammation in an engaging way.
A teenager being introduced to confocal microscopy using the INFLANET lego light sheet microscope.
INFLANET consortium gathered for the first time in Heidelberg in May 2022.
3D structures of newly carracterized zebrafish alarmins involved in inflammatory processes.
Zebrafish keratinocytes expressing ready to be released danger signals that will be realised after i
The consortium gathered for the 5th and final Conference in Visegrad in MArch 2024
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