Third Party Funds Group - Overall project
Acronym: SFB 1540 - EBM
Start date : 01.01.2023
End date : 31.12.2026
The central nervous system (CNS) is our most complex organ system. Despite tremendous progress in our understanding of the biochemical, electrical, and genetic regulation of CNS functioning and malfunctioning, many fundamental processes and diseases are still not fully understood. Recently, groups of several project leaders in this consortium, and a few other groups worldwide, discover an important contribution of mechanical signals to regulating CNS cell function. The CRC 1540 'Exploring Brain Mechanics' synergizes the expertise of engineers, physicists, biologists, medical researchers, and clinicians in Erlangen and Berlin to exploit mechanics-based approaches to advance our understanding of CNS function and, as a long-term vision, provide the foundation for future improvement of diagnosis and treatment of neurological disorders.
The central nervous system (CNS) is our most complex organ system. Despite tremendous progress in our understanding of the biochemical, electrical, and genetic regulation of CNS functioning and malfunctioning, many fundamental processes and diseases are still not fully understood. For example, axon growth patterns in the developing brain can currently not be well-predicted based solely on the chemical landscape that neurons encounter, several CNS-related diseases cannot be precisely diagnosed in living patients, and neuronal regeneration can still not be promoted after spinal cord injuries.
During many developmental and pathological processes, neurons and glial cells are motile. Fundamentally, motion is driven by forces. Hence, CNS cells mechanically interact with their surrounding tissue. They adhere to neighbouring cells and extracellular matrix using cell adhesion molecules, which provide friction, and generate forces using cytoskeletal proteins. These forces are transmitted to the outside world not only to locomote but also to probe the mechanical properties of the environment, which has a long overseen huge impact on cell function.
Only recently, groups of several project leaders in this consortium, and a few other groups worldwide, have discovered an important contribution of mechanical signals to regulating CNS cell function. For example, they showed that brain tissue mechanics instructs axon growth and pathfinding in vivo, that mechanical forces play an important role for cortical folding in the developing human brain, that the lack of remyelination in the aged brain is due to an increase in brain stiffness in vivo, and that many neurodegenerative diseases are accompanied by changes in brain and spinal cord mechanics. These first insights strongly suggest that mechanics contributes to many other aspects of CNS functioning, and it is likely that chemical and mechanical signals intensely interact at the cellular and tissue levels to regulate many diverse cellular processes.
The CRC 1540 EBM synergises the expertise of engineers, physicists, biologists, medical researchers, and clinicians in Erlangen to explore mechanics as an important yet missing puzzle stone in our understanding of CNS development, homeostasis, and pathology. Our strongly multidisciplinary team with unique expertise in CNS mechanics integrates advanced in vivo, in vitro, and in silico techniques across time (development, ageing, injury/disease) and length (cell, tissue, organ) scales to uncover how mechanical forces and mechanical cell and tissue properties, such as stiffness and viscosity, affect CNS function. We especially focus on (A) cerebral, (B) spinal, and (C) cellular mechanics. In vivo and in vitro studies provide a basic understanding of mechanics-regulated biological and biomedical processes in different regions of the CNS. In addition, they help identify key mechano-chemical factors for inclusion in in silico models and provide data for model calibration and validation. In silico models, in turn, allow us to test hypotheses without the need of excessive or even inaccessible experiments. In addition, they enable the transfer and comparison of mechanics data and findings across species and scales. They also empower us to optimise process parameters for the development of in vitro brain tissue-like matrices and in vivo manipulation of mechanical signals, and, eventually, pave the way for personalised clinical predictions.
In summary, we exploit mechanics-based approaches to advance our understanding of CNS function and to provide the foundation for future improvement of diagnosis and treatment of neurological disorders.