A5035371349- Nuclear Structure and Function
- RNA Research and Splicing
- Advanced Electron Microscopy Techniques and Applications
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Plant tissue culture and regeneration
- Supramolecular Self-Assembly in Materials
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Microbial Metabolic Engineering and Bioproduction
- Photosynthetic Processes and Mechanisms
- Plant Molecular Biology Research
- Cancer Research and Treatments
- Fungal and yeast genetics research
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Plant Taxonomy and Phylogenetics
- Electron and X-Ray Spectroscopy Techniques
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Biochemical and Molecular Research
University of Zurich
2019-2025
Novartis (Switzerland)
2023
Novartis Institutes for BioMedical Research
2023
ETH Zurich
2019-2022
Max Planck Institute for Developmental Biology
2018
Abstract Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across nuclear envelope (NE) 1–3 . These multi-megadalton structures are composed of about thirty different nucleoporins that distributed in three main substructures (the inner, cytoplasmic nucleoplasmic rings) around central channel 4–6 Here we use cryo-electron tomography on DLD-1 cells were prepared using cryo-focused-ion-beam milling to generate a structural model human NPC...
In this study, we describe the rapid identification of potent binders for WD40 repeat domain (WDR) DCAF1. This was achieved by two rounds iterative focused screening a small set compounds selected on basis internal WDR knowledge followed hit expansion. Subsequent structure-based design led to nanomolar potency with clear exit vector enabling DCAF1-based bifunctional degrader exploration.
While protein ubiquitination was long believed to be a truly eukaryotic feature, recently sequenced genomes revealed complete ubiquitin (Ub) modification operons in archaea. Here, we present the structural and mechanistic characterization of an archaeal Rpn11 deubiquitinase from Caldiarchaeum subterraneum, CsRpn11, its role processing CsUb precursor ubiquitinated proteins. CsRpn11 activity is affected by catalytic metal ion type, small molecule inhibitors, sequence characteristics at...
The nuclear pore complex (NPC) is the central portal for macromolecular exchange between nucleus and cytoplasm. In all eukaryotes, NPCs assemble into an intact envelope (NE) during interphase, but process of NPC biogenesis remains poorly characterized. Furthermore, little known about how assembly leads to fusion outer inner NE, no factors have been identified that could trigger this event. Here, we characterize transmembrane protein Brl1 as factor required NE in budding yeast. preferentially...
Selective transport across the nuclear envelope (NE) is mediated by pore complex (NPC), a massive ∼100-MDa assembly composed of multiple copies ∼30 proteins (Nups). Recent advances have shed light on composition and structure NPCs, but approaches that could map their organization in live cells are still lacking. Here, we introduce an vivo method to perform radial intensity measurements (NuRIM) using fluorescence microscopy determine average position NE-localized along nucleocytoplasmic axis....
Abstract The formation of large polymeric structures such as cytoskeletal and enzyme filaments is crucial for normal cellular function. However, can also form due to mutations that create self-interactions at the surface symmetric proteins. Often, proteins forming these maintain a folded state thereby differ from aggregates amyloids involve misfolding. We refer this type assemblies agglomerates mark difference. While cells have quality control mechanisms identify, buffer, eliminate misfolded...
Abstract The nuclear pore complex (NPC) is the central portal for macromolecular exchange between nucleus and cytoplasm. In all eukaryotes, NPCs assemble into an intact envelope (NE) during interphase, but process of NPC biogenesis remains poorly characterized. Furthermore, little known about how assembly leads to fusion outer inner NE, no factors have been identified that could trigger this event. Here we characterize transmembrane protein Brl1 as factor required NE in budding yeast....
All proteins interact with other cellular components to fulfill their function. While tremendous progress has been made in the identification of protein complexes, assembly and dynamics remain difficult characterize. Here we present a high-throughput strategy analyze native kinetics complexes. We apply our approach characterize co-assembly for 320 pairs nucleoporins (NUPs) constituting ~ 50 MDa nuclear pore complex (NPC) yeast. Some NUPs co-assemble fast via rapid exchange whereas others...