Multi-Scale Biology - Objectives

 

The goal of this initiative is to establish a platform for a range of research activities at RWTH Aachen University, including cardiovascular research, disease and stress signaling in plants, inflammation, mechanobiology, molecule design and synthesis, neurodegeneration, oncology, and stem cell research. Consequently, an interdisciplinary approach involving biochemists, cell biologists, chemists, computer scientists, mathematicians, physicians, physicists, plant biologists and structural biologists from several faculties of RWTH Aachen University, the Joint Research Center for Computational Biomedicine and various departments of Forschungszentrum Jülich is followed.

Integrating information obtained at many different levels/scales for improving human and animal health and for securing plant growth and yield is a major challenge in medicine and biology of today and will become significantly more important in the future. Particularly, the molecular functions of individual effector molecules, such as enzymes and bioactive compounds, their interaction with inhibitors/modulators, and their function in protein networks, cells, organs, organisms and crosstalk between organisms need to be understood and exploited. Various approaches can help to understand such multi-scale systems.

One of those approaches involves the use of libraries of small molecules to interfere with the functionality of a specified individual protein or bioactive compound. These targets can have various functions, e.g. in cancer, neurodegeneration or in the interaction of plants with pathogens. The identification of small molecules in such screens will not only provide information on the relevance of the target but will also open opportunities to interfere with the associated processes.

Another type of approach uses genetic screens, e.g. with shRNA libraries, to define novel components that target and/or cooperate positively or negatively with a relevant pathway by targeted interference. The recent technological developments allow the assessment and application of small molecules and genetic interference to a broad range of cell types and targets in an integrated approach for scanning and understanding both chemical and biological variation. Importantly these systems can also be used for identifying cooperative processes of cell fate control and of signaling networks. The obtained results are relevant for bridging the gaps between data from well-defined model systems and clinical applications and agricultural practices. Thus these approaches possess the capacity to address the heterogeneity of complex behavior e.g. in response to stress and in disease. They provide key methodological and mechanistic knowledge for efficient development of new paradigms for treating complex human and plant diseases with multi-factorial cause and for diseases associated with genetic instability, such as cancer.