New MBExC Groups

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New Professorship


Structural cell biology


Prof. Dr. Ruben Fernandez Busnadiego
Institute of Neuropathology
University Medical Center Göttingen
ruben.fernandezbusnadiego@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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New Research Group


Structural biology of protein quality control


Dr. Eri Sakata
Institute for Auditory Neuroscience & InnerEarLab
University Medical Center Göttingen
eri.sakata@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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New Junior Fellow


Biochemistry of membrane dynamics


Dr. Julia Preobraschenski
Institute for Auditory Neuroscience
University Medical Center Göttingen
julia.preobraschenski@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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New Junior Fellow


Bioluminescence imaging


Dr. Carola Gregor
Department of Optical Nanoscopy
Institute for Nanophotonics Goettingen e.V. (IFNANO)
carola.gregor@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.



New Junior Fellow


Auditory circuit analysis


Dr. Antoine Huet
Institute for Auditory Neuroscience
University Medical Center Göttingen
antoine.huet@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.

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Open Positions

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