February 18, 2025 at 12:15

SBBS introductory meeting for students 

If you missed the introduction meeting, feel free to contact one of the organisers by email or at the first seminar.

March 04, 2025 at 12:15, room U1.197

Probing the dynamics and interactions of disordered proteins with single-molecule spectroscopy: From disordered complexes to phase separation

The functions of proteins have traditionally been linked to their folded structures, but many proteins perform essential functions without being folded. Quantifying the highly dynamic and conformationally diverse ensembles of these intrinsically disordered proteins (IDPs) and their interaction mechanisms is an important aspect of understanding their functions. I will focus on highly charged IDPs and illustrate how single-molecule spectroscopy combined with simulations and other methods can be used to probe their dynamics, interactions, and phase separation.

Prof. Dr. Ben Schuler

Department of Biochemistry, University of Zurich

Zürich, Switzerland

SPECIAL SEMINAR: Friday April 11, 2025 at 12:15, room U1.191

Disordered but Decisive: Functional Roles of Disordered Regions in Proteins—Mechanistic Insights and Therapeutic Opportunities

Roughly a third of the human proteome contains disordered regions that play crucial functional roles, yet the molecular mechanisms governing how enzymes and transcription factors are regulated by their own disordered segments remain elusive. Nature employs these regions as on/off switches or molecular rheostats to fine-tune enzymatic activity, primarily through post-translational modifications. To tackle this challenge, we leverage cutting-edge NMR technology, with innovative biochemical strategies, including novel labeling schemes and protein semi-synthesis. This approach sheds light on the molecular determinants that control enzyme and transcription factor function, offering insights into the “structural” aspects of disordered protein regulation. 

Prof. Dr. Haribabu Arthanari

Dana-Farber Cancer Institute, Harvard Medical School

Boston, MA, USA

April 15, 2025 at 12:15, room U1.197

Exploring the molecular architecture of native actin assemblies using cryo-electron tomography

Actin contributes to an extraordinary range of cellular processes by assembling and disassembling highly dynamic and ordered structures. At the structural level, little is known about how the molecular players of the actin machinery work together inside cells to produce force-generating actin systems. In recent years, cryo-electron tomography (cryo-ET) has become the method of choice for structural analysis of the cell interior at the molecular level. In this talk, I will give a tour of our past and present cryo-ET work on different cellular actin structures and show how they have begun to open new avenues for understanding actin assembly in situ at the actin cytoskeleton-membrane interface.

Prof. Dr. Marion Jasnin

Helmholtz Pioneer Campus

Helmholtz Munich, Neuherberg

April 22, 2025 at 12:15, room U1.197

Novel macrocyclic peptide antibiotics against Gram-negative bacteria based on the Thanatin scaffold 

Resistance to antibiotics represent an enormous thread to mankind and the death toll due to antimicrobial resistances was recently estimated as 4.7 millions. As a consequence alternative antibiotics with novel mode of actions are desperately desired.

Recently, novel cyclic peptide antibiotics based on the protegrin scaffold were developed that target the lipopolysaccharide (LPS) transport pathway Lpt. They represent the first new class of antibiotics developed in the last 50 years.

We recently discovered that the naturally occurring peptide thanatin binds to LptA, that is part of the LPS transport bridge across the periplasm. In my presentation I will show examples of derivatives of thanatin, developed in collaboration with Spexis,  that bind to components of the periplasmic protein bridge involved in the LPS transport pathway. Peptide protein complexes are determined by solution NMR techniques and protein-peptide interactions binding affinities were determined by fluorescence polarization. By NMR and size-exclusion chromatography using suitably modified Lpt proteins LptA and LptC we could demonstrate that the protein bridge is completely dissembled upon addition of the peptides in vitro.

The peptides display low MICs even against many multi-resistant strains from the WHO ESKAPE priority list.

I will also describe the development of a mimic of LptD, using computational protein design, that is suitable for screening and binds to the cognate ligands LptA and Thanatin but does not contain the beta-barrel and hence is much easier to produce.

Prof. Dr. Oliver Zerbe

Department of Chemistry, University of Zurich

Zürich, Switzerland 

May 06, 2025 at 12:15, room U1.197

Cryo-Electron Tomography contributes to our understanding of bacterial interactions with their environment

How are bacterial cells able to actively seek out their preferred environmental niches? How can they evade toxins and predators? How do they interact with phages, each other and their host tissue? How can they adapt to thrive in changing environments? Cryo-electron tomography (cryo-ET) is our key research tool to gain insight into the structure and function of the molecular complexes involved in these behaviors. This technique allows us to directly study microbes in their native state at resolutions capable of visualizing individual proteins. Our research provides insight into chemotactic behavior of bacteria, which allows motile cells to detect changes in nutrient concentrations and to navigate towards preferential environments. We use this detailed knowledge for practical applications, such as the design of biosensors to detect human diseases. We are also investigating specific adaptations of chemotaxis systems of human pathogens that use this system for infectivity. When bacteria sense environmental changes, they can adapt themselves to survive, both structurally and metabolically. Consequently, cells of the same species may have vastly different morphological and behavioral characteristics depending on the environment they are in. We are investigating these morphological changes and their impact on the susceptibility to environmental stressors such as phage attacks.

Prof. Dr. Ariane Briegel

Institut Pasteur

Paris, France

May 20, 2025 at 12:15, room U1.197

NMR beyond Structures – The Endless Frontier

Artificial intelligence (AI) techniques led to impressive advancements in many disciplines and are transforming science and societies. While in structural biology the accurate predictions of protein structure from amino-acid sequences are clearly important and have become invaluable tools for structural biology research, they do have fundamental limitations in providing insights into, for example, the determinants of protein complex formation, protein conformational switching and resulting functional dynamics, let alone an adequate understanding of intrinsically disordered proteins (IDPs).  

These AI-inherent limitations therefore underscore the significance and future relevance of nuclear magnetic resonance (NMR) as a crucial experimental tool in filling these crucial knowledge gaps. IDPs are challenging the established structural biology structure-function paradigm and thus mandate suitable theoretical framework and concepts to properly address the subtle interdependence between protein structure and dynamics. In the lecture I will describe how the combination of NMR and novel computational protein sequence analysis tools can be used to provide a more comprehensive view of IDPs.

Additionally, NMR is attracting increasing attention in rational drug design, as fragment-based drug discovery relies on the initial discovery of weak binding ligands and subsequent improvement of non-covalent interactions between said ligands and the protein target. Here it will be shown that in contrast to a purely structure-focused approach NMR (in combination with sophisticated protein labeling techniques) can directly probe weak but specific intermolecular interactions, an essential information for the optimization of both affinity and selectivity.

Prof. Dr. Robert Konrat

Department of Structural and Computational Biology

University of Vienna, Max Perutz Labs

Vienna, Austria