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Funding objective

This funding line is intended to enable young scientists to test an innovative project idea for a 3R approach in a relatively uncomplicated manner, thereby strengthening the implementation of the 3R principle in everyday research. These can be, for example, projects to improve the translation to human (patho-)physiology through an alternative human model system, to promote the enhancement of animal welfare in animal testing, or to use in-silico approaches that affect the 3Rs. The proposals can refer to innovative project ideas where there is a high risk of failure.

Currently funded research projects

Crossroads of loading in joint health and disease: Mimicking mechanical overload in a xeno-free in vitro 3D artificial joint model

Immunofluorescence staining for the detection of fibrosis markers in an animal-free, mechanically stressed synovial organoid. Image credits: Alexandra Damerau.

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.

Multicellular liver platform for CRISPR perturbations in a complex human microenvironment

Immunofluorescence staining for various liver cell types in liver organoids from induced stem cells. Image credits: Julian Weihs

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.

Molecular mechanisms of mucociliary clearance regulation during airway inflammation

Using time-lapse recordings of fluorescent particles, it is demonstrated that interleukin-1ß reduces the beat frequency of cilia in nasal epithelial cell cultures from healthy subjects. Image credits: Tihomir Rubil

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.

Projects with completed funding

Pneumonia in vitro - Refinement of primary human lung models to study pulmonary infections

Alveolar organoids in matrigel. Image rights: Karen Hoffmann, Charité.

The aim of Karen Hoffmann's research approach is to develop animal free organotypic alveolar cultures - i.e. lung tissue consisting of the smallest branches of our airways, the so-called alveoli. In the future, the researcher wants to use these to study pulmonary bacterial infections. A key aspect in terms of the 3Rs is the cultivation of the complex primary in vitro models without the use of Matrigel. Matrigel consists of a complex mixture of biomolecules used as a growth medium in 3D cell culture and tissue engineering.

The disadvantage of Matrigel, however, is that it is produced  in mice by transplanting tumor cells and also contains the antibiotic gentamicin. The researcher is now aiming to establish two alternative models: a 3D organoid model based on alignate, a polysaccharide derived from brown algae, and a so-called air-liquid interface model. Both models will be compared with respect to their cellular composition and infected with the bacterium Pseudonomas.aeruginosa and a specific phage cocktail to assess their usability for bacterial infection studies and new therapeutic approaches. The aim is not only to improve the standardization of primary cell culture, but also to support the use of animal-free methods by replacing Matrigel.

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