The research interests of our group focusses on autoimmune mechanisms on central synaptic pathology.

Recent findings in patients with autoimmune encephalitis showed that these disorders are associated and presumably induced by highly specific autoantibodies against synaptic target structures, e.g. ionotropic receptors (NMDA, AMPA, Glycin receptors), G-protein coupled receptors (e.g. GABA-B receptors), or synaptic linker proteins (e.g. LGI1). The group of C. Geis investigates the effects of human autoantibodies on pre- and postsynaptic mechanisms. We have established passive-transfer mouse models with application of purified patient antibodies that are used to study the pathogenic effects of antibodies on animal behavior. Moreover, autoantibody-induced synaptic dysfunctions are evaluated in neuronal cell cultures, acute brain slices, and in-vivo using neurophysiological techniques. Super-resolution imaging techniques are used to investigate distinct antibody-induced morphological changes on the nanoscale level.

Another research focus is on pathomechanisms involved in sepsis associated encephalopathy. Here, the group of C. Geis uses a murine peritoneal contamination and infection model (PCI) to evaluate immune-mediated processes that may cause neuronal damage underlying cognitive deficits. Of particular interest is the role of microglia as the brain’s resident immune cells. Techniques used involve qPCR and RNASeq to analyze changes on the transcriptome level as well as immunohistochemical stainings of brain slices for morphological analyses. Several behavioural tests are performed to evaluate neurocognitive deficits after PCI. 

Learning and adaptation are fundamental properties of the brain, driven by the continuous remodelling of neuronal networks. Our research group at the Department of Neurology investigates the cellular and molecular mechanisms underlying dynamic structural and functional alterations in the young, aging and diseased brain, with a particular focus on adult neural stem cells and neurogenesis, and brain-immune interactions.

To address these topics, we employ cutting-edge neuroimaging techniques (e.g. magnetic resonance imaging, confocal microscopy), advanced molecular methods (e.g. single-cell sequencing, RNAscope), bioinformatics, behavioural testing, and interventional approaches to model disease in mice. 

During the upcoming summer course, we will introduce our research topics and molecular methods for investigating cell-type specific changes in the brain. Additionally, participants will gain hands-on experience in immunohistochemistry, confocal laser-scanning microscopy, and image analysis.

A) Electrophysiological recordings of stimulus-dependent responses in 2 different areas of the hippocampus. B) Mouse passing the Barnes maze test. C) Newborn neurons (purple) and D) newborn neuronal precorsor cells (purple) in the adult dentate granule layer. E) Tracing of a neuron residing layer II-III of the mouse motor cortex. F) MRI image of volumetric changes in rat model of cortical malformations.

Human brain development is prolonged and uniquely vulnerable: Although neurogenesis begins during embryogenesis, maturation processes such as synaptogenesis, myelination, and circuit refinement continue into early adulthood, shaping the mature brain. This extended window increases the brain's vulnerability to various genetic and environmental disruptions. Even subtle early disturbances can derail brain development trajectories, leading to neurodevelopmental disorders (NDDs) with irreversible, lifelong effects, highlighting a key challenge: determining when, where, and how early insults lead development toward pathology.
Human brain organoids have become powerful three-dimensional in vitro models derived from pluripotent stem cells that self-organize into structures mimicking early brain development. These include the organization of ventricular zone-like (VZ) and cortical progenitor populations, as well as primitive neuronal layers, offering insights into the cellular processes behind human
corticogenesis. Brain organoids provide a way to study mechanisms of human brain development and to model neurodevelopmental disorders that are challenging to examine in vivo due to limited tissue access and species differences in developmental pathways. When derived from patientspecific iPSCs, brain organoids have uncovered previously unknown cellular mechanisms involved in congenital malformations such as microcephaly, lissencephaly, and heterotopia. Besides, human brain organoids have also emerged as a novel and innovative experimental system to study and model devastating brain tumors such as glioblastoma.
The summer school training is intended to provide an introduction to human brain organoids and their applications to decoding human brain developmental and disease mechanisms, using specific neurogenetic diseases and glioblastoma as examples.

This course deals with the potential and the feasibilities of in vivo imaging of disease-related molecular markers in small laboratory animals. Namely, in vivo molecular imaging has been established to be a critical component of preclinical and translational biomedical research. It allows researchers to determine the biological structure and function of molecular markers by non-invasive means in situ in the body, i.e. without the withdrawal of tissue from the body for further analysis. This means that quantitative, spatial and temporal information on normal and diseased tissues can be determined, for example of those associated with cancer, inflammation or neurodegenerative diseases. Particular aims of such research activities are the discovery and analysis of disease-associated molecular interrelations, the elucidation of dedicated therapeutic effects, and validation of new drugs in the in vivo situation. There are several imaging modalities available for small animal imaging (e.g. mice and rat), such as whole body near infrared optical imaging, computed tomography (CT), positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance tomography (MR), etc.

In this course students will have the opportunity to get insights into: 1) the principles of the most important small animal molecular imaging modalities, 2) the construction of molecular imaging probes, 3) the basic requirements for animal experimentation, 4) the imaging of a local inflammation by utilization of small animal molecular imaging modalities, 4) the analysis of probe pharmacokinetics and the definition of physiological barriers counteracting to probe accessibility, and finally 5) the identification of potential pitfalls in image interpretation. Methods will cover areas concerning fluorescence microscopy, cytology, cell culture, optical spectroscopy, protein chemistry, pharmacology, disease models in mice, macroscopic optical imaging, CT imaging, histology, data analysis and statistics, etc.

Hands-on experience will be guided by experienced staff of the “Experimental Radiology Group”. All demonstrations and experimentation will be performed on state of the art devices and complemented with lectures on molecular imaging technology.

In order to transduce a signal of a hormone or prescription drug across the plasma membrane G-protein-coupled receptors (GPCRs) need to undergo conformational changes. The focus of our research is to investigate such conformational changes during GPCR activation and deactivation. Therefore we develop FRET-based probes for GPCRs to image the conformational change in living cells and millisecond time resolution. The use of such FRET-based sensors allows us to study receptor ligand interaction directly at the level of the receptor itself. Thus we are able monitor the effects of potential future drugs at the protein level and can correlate the observed data with effects on different signalling pathways triggered by receptor activation.

Receptor interaction with b-arrestin is an important regulatory key element in the termination of G-protein-dependent receptor signalling. The interaction of a GPCR and b-arrestin is regulated by ligand binding and receptor phosphorylation by specific receptor kinases. Since β-arrestins not only turn off G-protein-dependent-signalling but represent starting points for novel signalling cascades, we are also interested to investigate receptor ligands which are able to discriminate between G-protein and b-arrestin mediated receptor signalling. Such compounds are called biased ligands and are of great value for basic research and hold the promise for fewer side effects for patient treatment.

During the Summer School, we focus on real-time analysis of receptor activation in living cells using FRET based bio-sensors for the signal transduction pathways involved in receptor signalling. Applied techniques will include heterologous expression in mammalian cells, plate-reader assays and microscopy of signal transduction in living cells.

Aberrant gene regulation is a hallmark of cancer, and many oncogenic programs are driven by altered transcription factor binding to chromatin. In leukemia, these changes lead to impaired differentiation, dysregulated proliferation, and resistance to therapy, making leukemia a useful model system for studying disease mechanisms dependent on transcription factors.

A standard approach to measuring transcription factor occupancy is chromatin immunoprecipitation coupled with sequencing or targeted quantification. This approach has enabled genome-wide maps of protein-DNA interactions. However, conventional workflows can be limited by crosslinking chemistry, indirect interactions, and background signal. Photochemical, UV-based crosslinking provides a complementary approach because UV irradiation forms so-called zero-length crosslinks between nucleic acids and proteins in immediate contact. This enriches direct binding events in a time-resolved manner.

In this course, we will test the binding of CTCF, a master organizer of chromatin architecture, to selected DNA-binding sites in K562 cells.

Comparative analysis of CTCF ChIP-seq after ultraviolet (UV) laser light or formaldehyde (FA) fixation.
a) Examples of CTCF FA ChIP-seq (gray) and UV laser ChIP-seq using sonication (orange) or MNase digestion (blue) binding profiles at different genomic loci. (b) Venn diagram illustrating the number of detected binding sites in CTCF FA ChIP-seq (gray) and UV laser ChIP-seq after sonication (orange) or MNase digestion (blue).