Thecentral nervous system (CNS) is our most complex organ system. Despite tremendousprogress in our understanding of the biochemical, electrical, and geneticregulation of CNS functioning and malfunctioning, many fundamental processesand diseases are still not fully understood. For example, axon growth patterns inthe developing brain can currently not be well-predicted based solely on thechemical landscape that neurons encounter, several CNS-related diseases cannotbe precisely diagnosed in living patients, and neuronal regeneration can stillnot be promoted after spinal cord injuries.
Duringmany developmental and pathological processes, neurons and glial cells aremotile. Fundamentally, motion is drivenby forces. Hence, CNS cells mechanicallyinteract with their surrounding tissue. They adhere to neighbouring cells and extracellular matrix using celladhesion molecules, which provide friction, and generate forces usingcytoskeletal proteins. These forces aretransmitted to the outside world not only to locomote but also to probe themechanical properties of the environment, which has a long overseen huge impacton cell function.
Onlyrecently, groups of several project leaders in this consortium, and a few other groupsworldwide, have discovered an important contribution of mechanical signalsto regulating CNS cell function. For example, they showed that brain tissuemechanics instructs axon growth and pathfinding in vivo, that mechanicalforces play an important role for cortical folding in the developing humanbrain, that the lack of remyelination in the aged brain is due to an increasein brain stiffness in vivo, and that many neurodegenerative diseases areaccompanied by changes in brain and spinal cord mechanics. These first insights strongly suggest thatmechanics contributes to many other aspects of CNS functioning, and it islikely that chemical and mechanical signals intensely interact at the cellularand 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 mechanicsas an important yet missing puzzle stone in our understanding of CNSdevelopment, homeostasis, and pathology. Our strongly multidisciplinary teamwith unique expertise in CNS mechanics integrates advanced invivo, in vitro, and in silico techniques across time(development, ageing, injury/disease) and length (cell, tissue, organ) scalesto 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. Invivo and in vitro studies provide a basic understanding ofmechanics-regulated biological and biomedical processes in different regions ofthe CNS. In addition, they help identify key mechano-chemical factors forinclusion in in silico models and provide data for model calibration andvalidation. In silico models, in turn, allow us to test hypotheses without the need of excessive or even inaccessibleexperiments. In addition, they enable the transfer and comparison of mechanics data and findingsacross species and scales. They also empower us to optimise processparameters for the development of in vitro brain tissue-like matricesand in vivo manipulation of mechanical signals, and, eventually, pavethe way for personalised clinical predictions.
Insummary, we exploit mechanics-based approaches to advance ourunderstanding of CNS function and to provide the foundation for futureimprovement of diagnosis and treatment of neurological disorders.
The scientific focus of the Department of Neuroradiology is on multimodal imaging, especially in stroke, brain tumors, focal epilepsies, MS and dementia and on the minimally invasive treatment of cerebral aneurysms, vascular malformation, stenosis and acute stroke using state-of-the-art imaging technology including innovative flat-panel imaging and clinically approved ultrahigh-field 7 Tesla MRI.
Research projects
J111: Voxelomic Atlas: Single-Voxel Spatio-Spectral Homology Matching
(FAU Funds)
Immun-Checkpoints der Kommunikation zwischen Darm und Gehirn bei entzündlichen und neurodegenerativen Erkrankungen (GB.com)
(Third Party Funds Group – Overall project)
Funding source: DFG / Klinische Forschungsgruppe (KFO)
URL: https://www.kfo5024.med.fau.de/
Die Darm-Hirn-Achse ist ein bidirektionales Kommunikationssystem, das durch neurale, hormonelle, metabolische, immunologische und mikrobielle Signale gesteuert wird. Zelluläre und molekulare Faktoren aus dem Darm können die Funktion des Gehirns modulieren und neuere Erkenntnisse deuten darauf hin, dass eine gestörte Kommunikation entlang dieser Achse eine zentrale Rolle bei der Pathogenese von gastrointestinalen und neurologischen Erkrankungen spielt. In diesem Zusammenhang deuten klinische Studien darauf hin, dass Patienten mit chronisch-entzündliche Darmerkrankung (CED) ein erhöhtes Risiko aufweisen, später an Morbus Parkinson zu erkranken. Darüber hinaus wird ein Zusammenhang zwischen Multiple Sklerose und CED vermutet. Aufgrund des starken Zusammenhangs zwischen gastrointestinaler Entzündung und Neurodegeneration/Neuroinflammation hat sich das Konzept der pathologischen "Darm-Hirn-Achse" entwickelt. Veränderungen des Mikrobioms (Dysbiose), sowie die Translokation von bakteriellen Antigenen und Entzündungszellen/ löslichen Faktoren über die Darmbarriere und Blut-Hirn-Schranke werden als wichtige Faktoren für strukturelle und funktionelle Veränderungen im Zentralnervensystem (ZNS) angenommen. Während das Konzept einer Darm-Hirn-Achse zunehmend an Bedeutung gewinnt, ist eine eingehende Charakterisierung der Kommunikation zwischen beiden Organen begrenzt. Diese neuen Einblicke sind jedoch zwingend notwendig, um immunologische Schaltstellen dieses Netzwerk zu identifizieren. Das zentrale Ziel dieser klinischen Forschergruppe ist es daher, die Interaktionen zwischen dem Darm und Nervensystem entlang der Darm-Hirn-Achse bei immunvermittelten entzündlichen- und degenerativen Erkrankungen zu definieren. Die Verknüpfung der Forschungsschwerpunkte Immunologie und Neurowissenschaften ermöglich es uns dabei, einzigartige neue Erkenntnisse über die Pathogenese dieser Erkrankungen zu gewinnen, um somit die Grundlage zur Entwicklung neuer diagnostischer und therapeutischer Ansatzpunkte zu schaffen. Die Beeinflussung von Entzündungsprozessen in einem der beiden Organsysteme kann möglicherweise das Risiko minimieren, entlang dieser Achse entzündliche oder degenerative Begleiterscheinungen zu entwickeln. Um dieses Ziel zu verwirklichen, werden wir unserer Expertise im Bereich der präklinischen und klinischen Neuroimmunologie, Neurodegeneration, Gastroenterologie und mukolsalen Immunologie in einer Initiative vereinen und damit die traditionelle organzentrierte Betrachtungsweise von Entzündungsprozessen ersetzen. Unser langfristiges Ziel ist es dabei, die Mechanismen der Interaktionen von Darm und Gehirn im Detail zu entschlüsseln, um neue Biomarker und Zielstrukturen für Therapien zu identifizieren, neue therapeutische Ansätze zu entwickeln, mit denen Erkrankungen im Gastrointestinaltrakt und ZNS wirksam bekämpft oder sogar verhindert werden können. Hierdurch sollen neuartige Therapieansätze entwickelt werden.
Exploring Brain Mechanics (EBM): Understanding, engineering and exploiting mechanical properties and signals in central nervous system development, physiology and pathology
(Third Party Funds Group – Overall project)
Funding source: DFG / Sonderforschungsbereich / Transregio (SFB / TRR)
URL: https://www.crc1540-ebm.research.fau.eu/
Thecentral nervous system (CNS) is our most complex organ system. Despite tremendousprogress in our understanding of the biochemical, electrical, and geneticregulation of CNS functioning and malfunctioning, many fundamental processesand diseases are still not fully understood. For example, axon growth patterns inthe developing brain can currently not be well-predicted based solely on thechemical landscape that neurons encounter, several CNS-related diseases cannotbe precisely diagnosed in living patients, and neuronal regeneration can stillnot be promoted after spinal cord injuries.
Duringmany developmental and pathological processes, neurons and glial cells aremotile. Fundamentally, motion is drivenby forces. Hence, CNS cells mechanicallyinteract with their surrounding tissue. They adhere to neighbouring cells and extracellular matrix using celladhesion molecules, which provide friction, and generate forces usingcytoskeletal proteins. These forces aretransmitted to the outside world not only to locomote but also to probe themechanical properties of the environment, which has a long overseen huge impacton cell function.
Onlyrecently, groups of several project leaders in this consortium, and a few other groupsworldwide, have discovered an important contribution of mechanical signalsto regulating CNS cell function. For example, they showed that brain tissuemechanics instructs axon growth and pathfinding in vivo, that mechanicalforces play an important role for cortical folding in the developing humanbrain, that the lack of remyelination in the aged brain is due to an increasein brain stiffness in vivo, and that many neurodegenerative diseases areaccompanied by changes in brain and spinal cord mechanics. These first insights strongly suggest thatmechanics contributes to many other aspects of CNS functioning, and it islikely that chemical and mechanical signals intensely interact at the cellularand 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 mechanicsas an important yet missing puzzle stone in our understanding of CNSdevelopment, homeostasis, and pathology. Our strongly multidisciplinary teamwith unique expertise in CNS mechanics integrates advanced invivo, in vitro, and in silico techniques across time(development, ageing, injury/disease) and length (cell, tissue, organ) scalesto 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. Invivo and in vitro studies provide a basic understanding ofmechanics-regulated biological and biomedical processes in different regions ofthe CNS. In addition, they help identify key mechano-chemical factors forinclusion in in silico models and provide data for model calibration andvalidation. In silico models, in turn, allow us to test hypotheses without the need of excessive or even inaccessibleexperiments. In addition, they enable the transfer and comparison of mechanics data and findingsacross species and scales. They also empower us to optimise processparameters for the development of in vitro brain tissue-like matricesand in vivo manipulation of mechanical signals, and, eventually, pavethe way for personalised clinical predictions.
Insummary, we exploit mechanics-based approaches to advance ourunderstanding of CNS function and to provide the foundation for futureimprovement of diagnosis and treatment of neurological disorders.
Etablierung der Magnetresonanz-Elastographie an der FAU (Y)
(Third Party Funds Group – Sub project)
Term: 1. January 2023 - 31. December 2026
Funding source: DFG / Sonderforschungsbereich (SFB)
Etablierung der Magnetresonanz-Elastographie an der FAU (Y)
(Third Party Funds Group – Sub project)
Term: 1. January 2023 - 31. December 2026
Funding source: DFG / Sonderforschungsbereich (SFB)
Quantitative Charakterisierung von Fehlbildungen des Gehirns (A02)
(Third Party Funds Group – Sub project)
Term: 1. January 2023 - 31. December 2026
Funding source: DFG / Sonderforschungsbereich (SFB)
A02 stellt die zelluläre und extrazelluläre Zusammensetzung der menschlichen Hirnrinde unter physiologischen und pathophysiologischen Bedingungen quantitativ dar, z.B. genetisch definierte Fokale Kortikale Dysplasien und Polymikrogyrien. Darüber hinaus sollen mittels hochauflösenden und funktionellen MRT-Verfahren „Biomarker“ für unsere anatomisch-pathologischen und molekularen Befunde sowie visko-elastischen Messungen im Gehirngewebe (zusammen mit A01) ermittelt werden. Der Zugang zu menschlichem Hirngewebe ist ein herausragendes Merkmal von A02 und ergänzt die in EBM verfügbaren Tier- und Zellkulturmodelle.
2024
2023
2022
2021
2020
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