New Professorship
Dynamics of Excitable Cell Networks
Prof. Dr. Emilie Macé
University Medical Center Göttingen
c/o Max Planck Institute for Biological Intelligence
emilie.mace[at]bi.mpg.de
Prof. Dr. Emilie Macé
Systems neuroscience aims to understand the circuits and computations underlying behavior. However, one major challenge is that neuronal circuits span multiple spatial scales, from the level of the synapse to that of the entire brain. In our lab, we address this challenge using a novel method for recording whole-brain activity in behaving mice at high spatial resolution developed by Macé. We combine this technique functional ultrasound imaging (fUS), with optogenetic manipulations of targeted neuronal circuits and electrophysiological recordings.
One major goal of our team is to study how mice spontaneously switch between behaviors in a natural environment. We also study how sensory cues driving behavior switches are processed at the brain-wide level to inform behavior, with a focus on how salient visual objects are recognized by the brain. We hope that elucidating these fundamental principles may help better understand the dysfunction of behavioral control in some psychiatric disorders.
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Theory of Neuronal Systems
Prof. Dr. Viola Priesemann
Max Planck Institute for Dynamics and Self-Organization
and University of Göttingen
Prof. Dr. Viola Priesemann
Viola Priesemann investigates learning and self-organization in complex systems, such as the human brain. This living neuronal network shows highly optimized information processing; Viola investigates how information processing emerges based on local, unsupervised learning rules. To that end, she makes use of theoretical physics, information theory, and network science. Likewise, she also investigates the self-organization in social networks, from coordinated dyadic interactions and joint foraging, to the impact of threads like infectious disease, or news and fake-news on society. Across all these systems, the overarching goal is to identify, how local interactions between neurons or agents give rise to emergent function on the large scale. The understanding of these fundamentals may improve the initialization and effectiveness of future artificial neural networks, elucidate social dynamics, and shed light on the riddle of how our complex brains cope seemingly effortless with the complex environment. With her research focus on the analysis and theory of living networks, she makes a very important contribution to the overall research theme of the MBExC.
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Multiscale biology
Prof. Dr. Jan Huisken
Humboldt Professor of Multiscale Biology
University of Göttingen
jan.huisken[at]uni-goettingen.de
Prof. Dr. Jan Huisken
Jan Huisken’s professorship for Multiscale Biology is affiliated with the Faculty of Biology and Physiology. His research focuses on developmental biology using zebrafish as a key model organism. As a cofounder of modern light sheet microscopy and world-leading expert of non-invasive multiscale bioimaging, Jan uniquely combines physics and developmental biology, thus providing a strong link to the Faculty of Physics. His multiscale, light sheet microscopy methods are ideally suited to strengthen the MBExCs research scope with regard to precise analyses of the heart and brain from individual cells and their networks to the tissue level.
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Structural cell biology
Prof. Dr. Ruben Fernandez-Busnadiego
Institute of Neuropathology
University Medical Center Göttingen
ruben.fernandezbusnadiego[at]med.uni-goettingen.de
Prof. Dr. Ruben Fernandez-Busnadiego
Our research focuses on cutting-edge electron microscopy to reveal the intricate detail of cellular architecture. We combine cryo-FIB milling with cryo-electron tomography (cryo-ET) to image cells pristinely preserved by vitrification at molecular resolution.
One of our foci is the study of membrane contact sites (MCS), structures where two cellular membranes come into close apposition to directly exchange Ca2+, lipids and metabolites. We combine cryo-ET with molecular biology and functional assays to reveal the structural and functional roles of different MCS-resident proteins in situ, i.e. within their unaltered cellular environment.
Another major research area is the molecular architecture of neurons, both in their healthy state and in the context of neurodegenerative diseases. For example, our work has revealed the intricate structure of the presynaptic cytomatrix, a dense network of filaments linking synaptic vesicles to each other and to the active zone, likely playing important roles in the regulation of neurotransmitter release. We have also investigated toxic protein aggregates related to e.g. Huntington’s disease or amyotrophic lateral sclerosis. Our work reveals the broad diversity of such aggregates, both structurally and in terms of cellular interactions. These studies are shedding new light into the molecular mechanisms of neuron (dys)function.
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Dr. Eri Sakata
Institute for Auditory Neuroscience & InnerEarLab
University Medical Center Göttingen
eri.sakata[at]med.uni-goettingen.de
Dr. Eri Sakata
Our research addresses the fundamental mechanisms governing protein fate by the protein quality control system, particularly protein degradation by ubiquitin-proteasome system (UPS). We focus on unraveling how the molecular machineries for protein degradation execute their function and how the AAA+ ATPases, which are the main force generator of substrate unfolding and translocation, convert chemical energy to mechanical force. We answer these questions using cryo-electron microscope (cryo-EM) single particle analysis (SPA) and other biochemical and biophysical methods, providing the structural basis for conformational dynamics and regulatory mechanisms of protein assemblies.
Our cryo-EM studies have revealed that the conformational dynamics of the 26S proteasome are tightly related to executing its substrate processing functions. Nucleotide-binding pockets of the ATPase subunits were arranged in a coordinated manner, showing that ATP hydrolysis proceeds sequentially. We are seeking a deeper-understanding of the conformational dynamics of the proteasome and its regulatory mechanisms. Besides the proteasome, another AAA+ ATPase known as p97/Cdc48 plays key roles in substrate processing in the UPS. We aim to address the structural basis of the sequential substrate processing by p97 and the 26S proteasome. Our research will lead us to understand the mechanisms governing protein fate by these ATPases at the molecular and atomic levels.
My research group is part of the University Medical Center Göttingen, Institute for Auditory Neuroscience and the Multiscale Bioimaging Excellence Cluster (MBExC), providing us many exciting new directions and collaboration opportunities. We are going to investigate protein homeostasis in inner ear cells where the UPS plays an important role. In collaboration with the group of Prof. Tobias Moser, we also aim to understand the structural basis for the function of otoferlin, which is responsible for neurotransmitter release in inner hair cells.
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Dr. Thomas Frank
University of Göttingen
c/o Max Planck Institute for Biological Intelligence
thomas.frank[at]uni-goettingen.de
Dr. Thomas Frank
Our sense of smell is remarkable. For example, it is closely linked to past experience. A single familiar scent can bring back vivid memories - whether they be joyous memories of our childhood or difficult memories of traumatic experiences. But smells also influence our behavior more directly. The scent of delicious food can turn our heads, as long as we are hungry, while the smell of spoiled food makes us instinctively recoil. Our research tries to understand how the brain processes smells and how that leads to specific actions and flexible behaviors. To do this, we are studying the brains of a small fish called zebrafish, in which we study neuronal information processing at multiple scales, from synapses to whole brain networks. We study how information is transformed across different parts of the brain, such as areas that handle sensory information, form associations, and control movement. We use a combination of imaging, optogenetics, electrophysiology, genetics, behavioral approaches, and computational methods to observe, manipulate, and make sense of the activity of brain cells as the fish react to different smells in their environment. Our ultimate goal is to understand how past experience, internal states, and the environment can change the way the different parts of the brain work together to process sensory information and influence behavior.
Jun.-Prof. Dr. Nadja A. Simeth-Crespi
Institute of Organic and Biomolecular Chemistry
University of Göttingen
nadja.simeth[at]uni-goettingen.de
Jun.-Prof. Dr. Nadja A. Simeth-Crespi
In many biological and artificial networks stimuli-responsive processes play a crucial role. Signal-induced up- and downregulation of selected processes facilitate information transduction throughout the whole network and represents the basis for complex function. While light is an established traceless and precise external trigger for a wide range of applications, most systems are limited to the use of a single photoresponsive molecule and its regulation of one transformation. However, the rigorous modulation in a large (biological) network is based on the interplay of a series of external stimuli. We are determined to develop λ-orthogonal stimuli to control dynamically and externally various individual processes within the same system and in the presence of each another.
The group is located at the Institute for Organic and Biomolecular Chemistry and is part of the MBExC Cluster underlying the interdisciplinary character of our research program: our research dwells at the interface of physical and organic chemistry, and strives to incorporate biomolecules in chemical, biohybrid, and biomimetic systems. We focus on the orthogonality and cooperativity of (photo)chemical events to label molecules, build tools to understand complex function and bio(hybrid) networks.
Dr. Carola Gregor
Department of Optical Nanoscopy
Institute for Nanophotonics Goettingen e.V. (IFNANO)
carola.gregor[at]ifnano.de
Dr. Carola Gregor
Bioluminescence is a process by which living cells can emit light. It can be used to image living cells and organisms without external light and therefore without phototoxicity or photobleaching. Further, it enables the observation of light-sensitive processes and imaging with low background signal.
My research focuses on the bioluminescence system from bacteria. This system is fully genetically encodable and does not require the addition of an external luciferin substrate for imaging since the luciferin is synthesized and recycled by the cell. The genes of the bacterial bioluminescence system can also be introduced into mammalian cells, which enables autonomous bioluminescence imaging on the single-cell level.
Using the bacterial bioluminescence system, my group will develop new tools for biomedical imaging. We will explore strategies for the specific labeling of neurons and cardiomyocytes with high brightness for bioluminescence imaging of both cultured cells and living animals. Another goal is the generation of a genetically encoded bioluminescent calcium sensor for the observation of cellular activity in the heart and brain. We will use the developed tools to image calcium signaling, metabolic processes and cell death under healthy and disease conditions.
Dr. Antoine Huet
Institute for Auditory Neuroscience
University Medical Center Göttingen
antoine.huet[at]med.uni-goettingen.de
Dr. Antoine Huet
Acoustic information is encoded into a neural code by the synapses of inner hair cells with the spiral ganglion neurons (SGN). The resulting place, rate and temporal codes carried by the SGNs contain all the information about the acoustic environment. This neural code is integrated and refined by the neurons of the auditory brainstem to extract critical features about the acoustic scene.
Our group addresses the mechanisms underlying the integration of the auditory neural code in the brainstem with a strong focus on the refinement of the temporal code, the so-called “phase-locking enhancement”. In order to optically evoke phase-locking in the auditory pathway, we are also investigating photosensitizing tools, as optogenetics and photopharmacology.
Our research strategy combines: i) photosensitization of the SGNs and optical stimulation of the cochlea to precisely control the neural code statistic at the input of the auditory pathway; ii) single neuron recordings from the distinct neuronal populations constituting the network of interest; iii) information theory; iv) morphological imaging using confocal and light sheet microscopy; and v) computational modelling.
Our work will contribute to understand the integration of the neural code in the auditory pathway and its implication in physiological and pathological conditions (i.e. cochlear deafferentation). Our findings will be implemented in the coding strategies of the novel optical cochlear implant.
Dr. Julia Preobraschenski
Institute for Auditory Neuroscience
University Medical Center Göttingen
julia.preobraschenski[at]med.uni-goettingen.de
Dr. Julia Preobraschenski
Ferlins are a multi C2 domain protein family pivotal for vesicle fusion and trafficking. Members of the ferlin family are associated with detrimental pathogenic conditions such as deafness (otoferlin) and muscular dystrophy (dysferlin and myoferlin) in human patients. They are highlighted by their remarkably high number of C2 domains (5 to 7) and are additionally anchored in lipid membranes through their C-terminal transmembrane domain. Based on the Ca2+ ion and negatively charged lipid binding properties of their C2 domains, ferlins were initially viewed as Ca2+ sensors for membrane fusion events, similar to the well-studied family of synaptotagmins. However, novel findings suggest that ferlin family members play physiological roles beyond that, which to date remain poorly understood.
Thus, the goal of my group is to unravel the molecular mechanisms underlying ferlin function, as well as their alterations in human disease. To this end, we will combine state-of-the-art biochemical and biophysical methodologies with structural biology techniques encompassing single particle cryo electron microscopy and X-ray crystallography.
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