Live-Cell Imaging
The QueCellAI Initiative is maintaining multiple Incucyte® Live Cell Analysis Systems, which are located at UMG, the MPI for Multidisciplinary Sciences, as well as the University of Göttingen. The equipment is used by the collaboration partners to support their biomedical research. For this purpose, innovative image processing pipelines and new hardware modalities are integrated.
Translational Epigenetics Group
The group research focuses on dissecting the structure-to-function relationship of human chromosomes at the molecular level. We wish to understand how chromatin integrates the various signaling stimuli of its environment to control transitions between homeostatic and deregulated functional programs. We particularly ask how changes along the linear DNA fiber translate into dynamic higher-order regulatory networks. Ultimately, by deciphering the general rules governing transcriptional and chromatin homeostasis, we should be able to compile a parsimonious set of rules that allows prediction of how a cell will respond during ageing or in malignancy.
Contact: Prof. Dr. Argyris Papantonis
Translational Molecular Imaging
Main foci of our interdisciplinary research group “Translational Molecular Imaging” (Max-Planck Institute for Multidisciplinary Sciences/University Medical Center Göttingen) are the development of novel therapeutic strategies to improve patient outcomes. In a variety of aggressive, heterogeneous solid tumors (e.g. pancreatic ductal adenocarcinoma, PDAC) the current chemo-radiotherapies are largely ineffective, resistant tumor phenotypes develop, severe side effects occur and impaired penetration into the stroma-rich PDAC tumor tissue exists.
We propose to deliver high concentrations of chemotherapeutics selectively to tumor cells by validating a novel, site-specific drug delivery platform, through inorganic-organic hybrid nanoparticles (NP) consisting of cytotoxic drugs (>70% weight basis). The use of live cell imaging in this context is essential to track fluorescent dye-labeled NP uptake in cells, assess drug release and cytotoxic efficacy in cell and organoid-based assays.
Since the development of PDAC and selection of more aggressive cells is strictly connected with intracellular (pHi) and extracellular pH (pHe) changes, the effects of acute pHe changes and long-term acid-adaptation on PDAC growth are studied in the Incucyte using murine PDAC cells, either grown in physiological conditions (pH 7.4) or gradually adapted to pH 6.7.
Furthermore, immunotherapy is not yet effective in PDAC, which is partly due to a strongly immunosuppressive TME. We, therefore, co-culture PDAC cells and organoids with different fluorescently labeled immune- and stroma cells to monitor their interactions in dependence on novel nanoparticle-based vaccines.
Contact: Prof. Dr. Frauke Alves
Cellular Microenvironment for Pluripotent Mouse Embryonic Stem Cells
In recent years it became evident that the cellular microenvironment influences the fate of the cell through processes that were termed “mechanotransduction”. However, to what extent such mechanotransductive processes might influence the spatial organisation of the nucleus and chromatin features, and therefore the fate of a cell, is still largely unexplored. By precisely controlling the cellular microenvironment using nanotechnology, our team is interested in determining key players that regulate the cells’ life choices in response to the sensing of its microenvironment and how these mechanisms affect the dynamics of differentiation.
In summary our interest focuses on the characterization of the transcriptional regulation effects that substrate nanotopography can induce on pluripotent mouse embryonic stem cells (mESCs) and cancer models to understand how such effects may affect pluripotency and cell identity
Contact: Ph.D. Carmelo Ferrai
Auditory Neuroscience
Mammalian sound encoding relies on faithful and precise neurotransmission between cochlear inner hair cells (IHC) and afferent spiral ganglion neurons. To master this challenging task, the presynaptic active zones of IHCs are equipped with presynaptic specializations – termed 'synaptic ribbons' – that facilitate high rates of vesicular release and subsequent replenishment, even during prolonged periods of ongoing stimulation. While the molecular architecture and function of mature ribbon-type active zones has been an area of intense research, the processes underlying presynaptic development prior to hearing onset still remain largely enigmatic. Hence, the Vogl group primarily focuses on developmental aspects of IHC synaptogenesis and functional synaptic maturation in living and structurally-intact mammalian inner ear preparations. For this purpose, their work employs AAV-mediated gene manipulation of cochlear cell types in combination with electrophysiology, optogenetics and a range of advanced light-microscopic imaging techniques (e.g., multi-plane muti-color wide-field, confocal and stimulated emission-depletion [STED] microscopy) to decipher the molecular determinants and – in particular – the temporal sequence of presynaptic active zone formation during early postnatal development in mice. Here, their research relies heavily on various live-cell imaging paradigms for long-term multi-color tracking of fluorescently-labelled synaptic components.
Contact: Dr. Christian Vogl