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Immunofluorescence staining of different liver cell types in induced pluripotent stem cell derived liver organoids. Copyright: Julian Weihs



Charité 3R honours three young researchers with the Young Investigator Award 2023

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For the development of three different organ models from human tissue, Alexandra Damerau, Julian Weihs and Tihomir Rubil will receive this year's 3Rs Young Investigator Award. The award is intended to enable young researchers to test out an innovative project idea for a 3Rs approach in order to strengthen the implementation of the 3Rs principle in everyday research. The aim of the 3Rs principle is to avoid animal experiments wherever possible (Replace), to reduce the number of animals used in experiments (Reduce) and to limit their suffering to the indispensable level (Refine). The three projects were selected from a total of 20 high-quality applications by the Charité 3R Spokesperson's Council and two additional experts in an anonymous review process. The prize is endowed with 15.000 euros per project.

In the project "Crossroads of loading in joint health and disease: Mimicking mechanical overload in a xeno-free in vitro 3D artificial joint model", a three-dimensional joint model grown from human cartilage and connective tissue cells is to be further developed in such a way that mechanical forces that normally act on joints are taken into account. The assumption is, that mechanical stress on joints contributes significantly to the development of osteoarthritis (OA), the most common chronic, degenerative joint disease and the main cause of age-related limitations. However, the explicit influence of mechanical forces in the development and progression of the disease has been poorly investigated so far. Dr. Alexandra Damerau, together with her colleagues Dr. Moritz Pfeiffenberger and Dr. Timo Gaber from Prof. Frank Buttgereit's working group at the Department of Rheumatology and Clinical Immunology, would like to develop a system with which disease processes triggered by mechanical stimuli can be researched in an animal-free, controlled environment. The aim is to identify and understand the key mechanism of the pathological forces that occur in OA.

Julian Weihs, a doctoral student in the research group of Dr. Milad Rezvani from the Department of Paediatrics with a focus on gastroenterology, nephrology and metabolic medicine, wants to establish a liver platform derived from various human stem cells in order to analyze genetic factors of chronic liver diseases in complex human systems. Here, the term platform refers to the organ model itself, which allows the investigation of various questions. This is because the platform carries a CRISPR system integrated into the cells, which can specifically change the expression of many different genes. In this way, different genes and their effects can be evaluated in an organ-like context in vitro. The aim of his project "Multicellular liver platform for CRISPR perturbations in a complex human microenvironment" is to better understand mechanisms of chronic liver diseases at the level of gene products in order to identify new gene therapies, together with the central facilities for stem cells as well as genomics at BIH.

Tihomir Rubil, PhD student in Prof. Marcus Mall's research group at the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, is investigating the so-called "mucociliary clearance" (MCC)"- an important protective mechanism of the lungs that keeps the airways free of inhaled pathogens and pollutants. In his project "Molecular mechanisms of mucociliary clearance regulation during airway inflammation", the mechanisms that regulate this disease will be investigated in healthy and sick persons at the cellular and molecular level. Cell culture models from primary human respiratory epithelial cells will be used to model the physiological processes of MCC, reducing the need for animal experiments and supporting the 3Rs principle. Using these models, the researchers aim to investigate the cellular processes and protein-level changes associated with pro-inflammatory conditions.  The analyses will be carried out in collaboration with the BIH Flow & Mass Cytometry Core Facility and the Charité High-Throughput Mass Spectrometry Core Facility.

Further information on the funded projects and further Charité 3R funding lines can be found here. Charité 3R wishes the three award winners every success in implementing their ideas and hope that this will result in further 3R projects and applications. To all applicants who did not receive funding this time, Charité 3R wishes good luck with future applications and other creative ways to implement the ideas.



Charité 3R

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