Mitochondria are essential cell organelles that are best known for their function in cellular energy homeostasis. However, research in the last two decades has unravelled an unexpected complexity of mitochondria and multiple ways how mitochondria interact with their cellular environment. Mitochondria are now recognised as dynamic and plastic organelles that are integrated into a complex network of cellular signalling cascades. They respond to alterations in cellular physiology but by themselves signal to determine cell fate and function. These complex and bi-directional interactions of mitochondria with the cell make it also necessary to revise the view on the role of mitochondria in disease. The CRC will tackle the challenge of mitochondrial complexity using novel interdisciplinary and collaborative approaches. The planned projects in research area A will examine how mitochondrial function adapts to changing physiological demands focussing on mitochondrial plasticity and the regulatory role of mitochondrial dynamics in preserving the functional integrity of mitochondria and the cell. Work in research area B examines the role of mitochondrial signalling under various stress conditions and in disease. Together, the planned experiments in the CRC will foster our understanding as to how mitochondria regulate cell function and therefore will provide new insight into the cell-type specificity of mitochondrial diseases.
Cell death is a fundamental biological process that is critical for the maintenance of tissue homeostasis and plays a central role in host-microbe interactions and pathogen defence in both animals and plants. The recent discoveries of molecularly controlled pathways of lytic cell death, such as necroptosis, pyroptosis and ferroptosis, revealed that cells can select between different modalities of regulated cell death (RCD) and instigated the concept that the consequences of cell death at the tissue and organismal levels are profoundly affected by the way a cell dies. Dying cells regulate tissue responses by engaging in an intimate cross-talk with bystander cells, yet it remains unclear how the type of cell death determines the outcome of this interaction.
The overarching goal of this CRC is to understand the mechanisms of regulation and the functional and physiological consequences of diverse forms of RCD in organismal physiology and pathology, with particular focus on immunity, inflammation and host-microbe interactions. By combining multi- and inter-disciplinary approaches, this CRC aims to provide answers to fundamental outstanding questions in cell death research and aspires to make major contributions to the better understanding of the regulation and function of the different forms of RCD in organismal physiology and pathology and the underlying mechanisms.
In order to achieve this, work in two Research Areas focuses on the regulation and function of cell death in organismal homeostasis and disease, and on the mechanisms and function of RCD in host-microbe interactions.
The motor system enables us to interact with the environment. The variety of motor activity ranges from simple monosynaptic reflexes to complex behaviour, e.g., tool use, all of which rely on coordinated interaction between neurons and muscles. Motor control, i.e., the neural mechanisms that enable muscle activation in a coordinated and meaningful manner, ensures the stability and integrity of our body in its environment. Compared to sensory, cognitive, or affective-emotional systems, the performance of the motor system is particularly easy to quantify in terms of the observable motor effect and can be compared across species. In studying the neural mechanisms underlying motor control, the comparison of motor behavioral parameters across species offers a special opportunity to bridge the gap between molecular, cellular, and systemic levels. This also has clinical relevance: the motor system is affected in many, if not all, neurological and psychiatric disorders. Therefore, a more comprehensive understanding of the motor system will advance our knowledge of the neural basis of neurological and psychiatric disorders. In interplay, neuropsychiatric disorders provide new insights into the (dys)function of the motor system and lend themselves to targeted testing of models of motor control.
The Collaborative Research Center (CRC) 1451 brings together neuroscientists investigating genetic factors, cellular and synaptic, and system/neuronal network processes underlying motor control in animals and humans, both in healthy individuals and in neuropsychiatric disorders. All investigators are committed to the multi-faceted, iterative and integrative agenda of the CRC, with the long-term goal of identifying the essential mechanisms underlying normal and pathological motor control. The research topic and the comprehensive, interdisciplinary and collaborative approach are unique in Germany. The CRC will provide new insights into the genetic, cellular and systemic mechanisms that contribute to motor precision, coordination, flexibility and moto learning (Research Area A). Research will also be conducted on how these mechanisms develop or change across the lifespan (Research Area B). Finally, studies of disease-related motor control disorders (Research Area C) will a) allow validation of models of physiological motor control and its development, b) improve our understanding of neurological and psychiatric disorders that lead to motor impairments, and c) provide new perspectives for their treatment.