A5000485385- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Particle accelerators and beam dynamics
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Full-Duplex Wireless Communications
- Polyomavirus and related diseases
- Enzyme Structure and Function
- Legionella and Acanthamoeba research
- Antenna Design and Analysis
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
- Magnetic confinement fusion research
- Toxoplasma gondii Research Studies
- Particle Detector Development and Performance
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Particle Accelerators and Free-Electron Lasers
- Autophagy in Disease and Therapy
- Advanced biosensing and bioanalysis techniques
- Protein Structure and Dynamics
- Superconducting Materials and Applications
- Enzyme Production and Characterization
- Cancer Mechanisms and Therapy
University of Zurich
2023-2025
European Molecular Biology Laboratory
2019-2024
University of Tübingen
2018-2019
Bernstein Center for Computational Neuroscience Tübingen
2019
University of British Columbia
2017
During normal cellular homeostasis, unfolded and mislocalized proteins are recognized removed, preventing the build-up of toxic byproducts1. When protein homeostasis is perturbed during ageing, neurodegeneration or stress, can accumulate several forms chemical damage through reactive metabolites2,3. Such modifications have been proposed to trigger selective removal chemically marked proteins3-6; however, identifying that sufficient induce degradation has remained challenging. Here, using a...
The Integrator is a specialized 3′ end-processing complex involved in cleavage and transcription termination of subset nascent RNA polymerase II transcripts, including small nuclear RNAs (snRNAs). We provide evidence the modular nature by biochemically characterizing its two subcomplexes, INTS5/8 INTS10/13/14. Using cryoelectron microscopy (cryo-EM), we determined 3.5-Å-resolution structure INTS4/9/11 ternary complex, which constitutes Integrator's catalytic core. Our reveals spatial...
RNA polymerase II (RNAPII) controls expression of all protein-coding genes and most noncoding loci in higher eukaryotes. Calibrating RNAPII activity requires an assortment polymerase-associated factors that are recruited at sites active transcription. The Integrator complex is one the elusive transcriptional regulators metazoans, deemed to be after initiation help establish modulate paused RNAPII. known composed 14 subunits assemble operate a modular fashion. We employed proteomics...
Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This achieved via two enzymatic activities, RNA endonuclease phosphatase, acting on the promoter-proximally paused polymerase Ⅱ (RNAPⅡ). Yet, it remains unclear how assembly recruitment are regulated what functions many its core subunits are. Here, we report structures human sub-complexes: INTS10/13/14/15 INTS5/8/10/15, an integrative model fully assembled bound to...
Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense attacking intracellular pathogens and inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression absence IFN-γ killed cells induced Golgi fragmentation. exposure improved macrophage survival through activity kinase PIM1. PIM1...
MCPyV is the first polyomavirus directly implicated in development of an aggressive human cancer, Merkel cell carcinoma (MCC). Although constantly shed from healthy skin, MCC incidence increases among aging and immunocompromised individuals. To date, events connecting initial infection subsequent transformation still remain elusive. differs other known polyomaviruses concerning its tropism, entry receptor requirements, kinetics. In this study, we examined cellular requirements for endocytic...
Abstract The metazoan tRNA ligase complex (tRNA-LC) has essential roles in biogenesis and unfolded protein response. Its catalytic subunit RTCB contains a conserved active-site cysteine that is susceptible to metal ion-induced oxidative inactivation. flavin-containing oxidoreductase PYROXD1 preserves the activity of human tRNA-LC NAD(P)H-dependent manner, but its protective mechanism remains elusive. Here, we report cryogenic electron microscopic structure RTCB–PYROXD1 complex, revealing...
Summary Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs in Metazoans. This achieved via Integrator’s two enzymatic activities, RNA endonuclease phosphatase, acting on the promoter-proximally paused Polymerase II (RNAPII). Yet, it remains unclear how assembly recruitment are regulated what functions many its core subunits. Here we report cryo-EM reconstructions large sub-complexes: INTS10/13/14/15 (Arm module)...
Polysialic acid (polySia) is a homopolymeric saccharide that associated with some neuroinvasive pathogens and found on selective cell types in their eukaryotic host. The presence of polySia capsule these bacterial helps resistance to phagocytosis, cationic microbial peptides bactericidal antibody production. biosynthesis catalysed by single polysialyltransferase (PST) transferring sialic from nucleotide-activated donor lipid-linked acceptor oligosaccharide. Here we present the X-ray...
Abstract RTCB is the catalytic subunit of metazoan tRNA ligase complex (tRNA-LC) that plays essential roles in biogenesis and unfolded protein response. The center contains a conserved cysteine susceptible to metal ion-induced oxidative inactivation. flavin-containing oxidoreductase PYROXD1 preserves activity mammalian tRNA-LC NAD(P)H-dependent manner, but its protective mechanism remains elusive. Here we report cryo-EM structure human with PYROXD1, revealing directly interacts through...
Heparin is a polymeric carbohydrate with variety of biomedical applications that particularly challenging from synthetic point view. Here, we present the synthesis carbohydrate-polymer based hybrid structures by combining defined heparin fragments monodisperse, sequence-controlled glycooligo(amidoamines) suitable as glycan mimetic model compounds demonstrated STD-NMR binding studies viral capsids.
Abstract Merkel Cell Polyomavirus (MCPyV) is a small, non-enveloped tumor virus associated with an aggressive form of skin cancer, the cell carcinoma (MCC). MCPyV infections are highly prevalent in human population virions being continuously shed from skin. However, precise host tropism(s) remains unclear: able to replicate within subset dermal fibroblasts, but DNA has also been detected variety other tissues. appears different polyomaviruses as it requires sulfated polysaccharides such...