Important information:
We are very excited to introduce you to the eight speakers that will present their research at this year's Ulm Biophysics Symposium on October 9th, 2026!
Get more information on the talk by clicking on the speakers name:
Illuminating the Regulation of Gene Expression at the Single-Molecule Level
Abstract: Chromatin structure controls access to genetic information and is dynamically shaped by ATP-dependent chromatin remodelers, enzymes linked to cancer and developmental disease. In this seminar, I will present single-molecule imaging methods that track DNA movement within nucleosomes in real time, revealing how remodeling intermediates are coordinated with ATPase activity and how efficiently ATP hydrolysis is coupled to DNA translocation. I will also discuss a high-throughput platform combining single-molecule measurements with next-generation sequencing to uncover sequence-dependent mechanisms in diverse nucleic acid transactions.
Information flow in self-organized developmental systems
Abstract: Embryonic development relies on multi-cellular systems self-organizing into precise spatial patterns of cell fates. An inevitable obstacle is intrinsic noise at the single-cell level, which constrains the information available to cells for fate decisions. This information is often considered to be encoded in extracellular morphogen concentrations, but cells respond to a much broader set of inputs, including dynamical and combinatorial signaling as well as mechanosensitive pathways that sense tissue mechanics. Yet we lack principled frameworks to quantify and predict how cells obtain sufficient information to reliably differentiate into the right fate at the right time and place. I will discuss how combining biochemical and mechanical models of patterning and morphogenesis with information theory provides a mathematical language for analyzing biological self-organization across diverse systems. First, I will demonstrate how the coupling between mechanosensitive YAP1 signaling and lateral inhibition governs diverse epithelial organoids, from intestinal to mammary. We develop a unifying model for these systems and analyze it using information theory. Second, I will discuss how richer inputs, from mechanical gradients to combinatorial signaling, can be incorporated into this framework. This opens an avenue toward unifying the zoo of chemical and mechanical signaling processes that orchestrate embryonic development.
Studying Cell Signal Initiation with Multiparametric Fluorescence Image Spectroscopy, Nanoscopy, and Superparamagnetic Nanoparticles
Abstract: Measuring protein interaction and localization at the single-molecule level on cells remains challenging, in particular when molecular oligomerization states are to be distinguished. For this reason, we use a multiparametric spectroscopic approach to provide quantitative insights. Timeresolved FRET live-cell experiments are used to measure the supramolecular state of receptors on the cell membrane. As orthogonal measures, super-resolved STED images and molecular brightness approaches are combined, to reveal the supramolecular size and molecular concentrations on the membrane, in order to probe cell signal initiation models. We further introduce superparamagentic nanoparticles as activatable sensors to actively target and manipulate subcellular molecules. We use them to explore the subcellular architecture and the biomolecular dynamics that are important for cell signal generation.
From DNA Nanotechnology to Biomedical Insight – Towards Single-Molecule Spatial Omics
Abstract: Super-resolution fluorescence microscopy is a powerful tool for biophysical and biological research. The transient binding of short fluorescently labeled oligonucleotides (DNA-PAINT) can be leveraged for easy-to-implement multiplexed super-resolution imaging that achieves molecular-scale resolution across large fields of view. This seminar will introduce recent technical advancements in DNA-PAINT including approaches that achieve sub-10-nm spatial resolution and spectrally unlimited multiplexing in whole cells followed by recent developments in novel protein labeling probes that have the potential to facilitate DNA-barcoded labeling of much of the proteome within intact cellular environments.
Applications of these new approaches will be discussed in cell surface receptor imaging and neuroscience. Visualization and quantification of cell surface receptors at thus far elusive spatial resolutions and levels of multiplexing yield fundamental insights into the molecular architecture of surface receptor interactions thus enabling the future development of more refined “pattern”-based therapeutics. A key approach in implementing these methods has been to leverage standard off-the-shelf fluorescence microscopy hardware as a tool for spatial omics, thus democratizing the ability to visualize most biomolecules and probe their network-wide interactions in single cells, tissues, and beyond with single-molecule-based "Localizomics”.
Optimal signal processing in gene regulation
Abstract: Gene needs to be expressed precisely enough for the organism to be able to develop healthily; yet, the signals that determine gene expression and their processing are subject to stochastic fluctuations.
In this talk, I will show that we can better understand how animals regulate genes by assuming that this regulation optimizes information flow from signals to the relevant function. I will show that this applies both to the regime of precise and of noisy gene regulation, on two examples. First, I will discuss the design of regulatory regions of binding sites on the genome in early fly embryo development, where these regions regulate patterning genes with high precision. These regions involve clustering transcription factors, and activate genes non-monotonically; both these features emerge from assuming that information flow is optimized. Second, I will discuss what we can learn about naturally occurring signals from a population of cultured stem cells exposed to Wnt stimuli, where it is unclear what type of Wnt signal is read by these cells. While the expression of downstream genes appears highly noisy, we can show that with discrete and appropriately chosen signals, the cellular response can be precise enough to allow reliable differentiation into two distinct states. The emergent discrete signals show an intricate phase diagram and may occur more generally, as a consequence of noisy processing.
Chasing viruses and extracellular vesicles to understand their interactions with cells
Abstract: Light microscopy remains an invaluable method for advancing our mechanistic understanding of cellular structure and dynamic processes. Here, we report on the combination of label-free and fluorescence microscopy modalities with a capillary-based controlled virus delivery system for investigating the intricate interplay between cellular membranes and virions during the infection process. This approach allows us to dissect binding and entry dynamics at the subcellular level with unprecedented nanoscopic detail, offering a significant advantage over traditional strategies by simultaneously visualizing both the viral particle and the dynamic cellular membrane in 3D. Our investigations indicate various stages of viral interaction: initial diffusion towards the cell surface, early and transient binding events, and subsequent stable adherence. Furthermore, by tracking infected cells over many hours, we study slow processes such as the subsequent transmission of these virions. This long-term observation capability sheds light on the nanoscale intricacies of the viral lifecycle and provides mechanistic insights into how viruses manipulate cellular machinery for their own propagation.
Self-organization of active epithelial mechanics
Abstract: Animal development requires large numbers of cells to choreograph their force generation in order to sculpt tissues and organs. While much is known about the corresponding large scale tissue flow and its genetic drivers, fundamental questions regarding the underlying tissue mechanics and local control of cellular force generation remain open. We address these questions in the context of the shape changes of epithelial sheets. We leverage the fact that cellular forces equilibrate rapidly compared to the speed of development to model the epithelial sheet as a network of balanced junctional tensions – a “distributed hydrostatic skeleton”. This model admits an elegant geometric formulation that we use to investigate how cells remodel the tension network to change tissue shape. We find that a simple "winner-takes-all" mechanical feedback loop can self-organize complex cell movement, matching experimental data on the cell and tissue scale. We find that the ability to self-organize depends on initial order in the cellular packing. Our model explains how embryo geometry, cellular packing geometry, and top-down genetic patterning impinge on bottom-up cellular self-organization to determine tissue shape change.
Reconstructing human brain development with organoid and single-cell technologies
Abstract: To be added soon
The Ulm Biophysics Symposium 2026 is supported by:
