Time-resolved high throughput imaging of membraneless organelles to organ models

• Subject Area: Biochemistry ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533312446

The secure supply of the population with established and newly developed drugs is essential for ensuring a functioning healthcare system and is currently the focus of public interest due to supply shortages. The h_da is researching the development of new concepts for the discovery and production of active substances using sustainable processes. Within the framework of the DFG Research Impulse Program (FIP), the expertise of eight working groups from three disciplines has been combined to make the process of drug discovery more sustainable. Here we are applying for a high-throughput microscope to optimize the new methods for drug screening, to expand on other methods that are important for clinical translatability, such as organ-on-a-chip systems, and to enable systematic, standardized characterization of biomolecular condensates. Biomolecular condensates are currently in the spotlight of biochemical and cell biological research. Many processes seem to be regulated by this form of compartmentalization in cells. However, there is disagreement about the relevance of the biochemical observations for cell biological processes. This could be improved by standardizing and systematically analyzing the conditions under which the condensates form. We want to contribute here by establishing a platform for the study of biomolecular condensates with high-throughput microscopy that is available to the entire scientific community. By comparing results from different laboratories over an extended parameter space, we will gain a better understanding of the phenomenon and its biological significance. Based on this, we will use the platform to develop drugs and drug conjugates (e.g. with nanoparticles) that (de)stabilize or detect these structures. In addition, the microscope to be acquired will be used to develop organ-on-a-chip systems with which, among other things, the interaction of nanoparticles with cell systems can be investigated. In the future, such methods could significantly reduce the number of animal experiments in the development of active substances and thus make the process more sustainable. Furthermore, by using human (patient) cells and mimicking (patho)physiological conditions, these models help to improve the clinical translatability of preclinical data. The new research infrastructure will radiate into large parts of the h_da (e.g. departments of plastics technology, computer science, mathematics and natural sciences and media) and contribute to increased collaboration with working groups at the TU Darmstadt. Collaboration with working groups at ETH Zurich will make a valuable contribution to the internationalization of the h_da and offer new starting points for future research cooperation.

• DFG Programme: Major Instrumentation Initiatives
• Major Instrumentation: High.Throughput-Mikroskop „ImageXpress Confocal HT.ai“
• Applicant Institution: Hochschule Darmstadt
• Leader: Professor Dr. Heinz Neumann
• Co-Investigators: Professor Dr. Michael Becker; Professorin Dr. Christina Graf; Professor Dr. Franz-Josef Meyer-Almes; Professor Dr. Frank Schael; Professor Dr. Andreas Weinmann