A5016384712- Protein Structure and Dynamics
- Enzyme Structure and Function
- Redox biology and oxidative stress
- Prostate Cancer Treatment and Research
- Catalysis and Oxidation Reactions
- Mass Spectrometry Techniques and Applications
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- Xenotransplantation and immune response
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Legionella and Acanthamoeba research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Metal-Catalyzed Oxygenation Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Cancer Cells and Metastasis
- Cellular transport and secretion
- Catalytic Processes in Materials Science
- Metalloenzymes and iron-sulfur proteins
- Genomic variations and chromosomal abnormalities
- Synthesis of Tetrazole Derivatives
- Biomedical Research and Pathophysiology
- Heat shock proteins research
ETH Zurich
2019-2022
Suzuki (Japan)
2020
European Molecular Biology Laboratory
2010-2016
Paul Scherrer Institute
2013-2014
Swiss Light Source
2013
University of Zurich
2004-2012
European Molecular Biology Laboratory
2011
Argonne National Laboratory
2011
The ability of circulating tumor cells (CTCs) to form clusters has been linked increased metastatic potential. Yet biological features and vulnerabilities CTC remain largely unknown. Here, we profile the DNA methylation landscape single CTCs from breast cancer patients mouse models on a genome-wide scale. We find that binding sites for stemness- proliferation-associated transcription factors are specifically hypomethylated in clusters, including OCT4, NANOG, SOX2, SIN3A, paralleling...
Abstract Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA whole-exome sequencing the PDX organoids confirmed transcriptomic genomic similarity primary tumor. PNPCa harbors BRCA2 CHD1 somatic mutations, shows SPOP/FOXA1 -like signature microsatellite...
Pancreatic cancer (PDAC) is a highly aggressive malignancy for which the identification of novel therapies urgently needed. Here, we establish human PDAC organoid biobank from 31 genetically distinct lines, covering representative range tumor subtypes, and demonstrate that these reflect molecular phenotypic heterogeneity primary tissue. We use CRISPR-Cas9 genome editing drug screening to characterize drug-gene interactions with ARID1A BRCA2. find missense- but not frameshift mutations in...
Asparagine-linked glycosylation is a common posttranslational modification of diverse secretory and membrane proteins in eukaryotes, where it catalyzed by the multiprotein complex oligosaccharyltransferase. The functions protein subunits oligoasccharyltransferase, apart from catalytic Stt3p, are ill defined. Here we describe functional structural investigations Ost3/6p components yeast enzyme. Genetic, biochemical analyses lumenal domain Ost6p revealed oxidoreductase activity mediated...
Drosophila Nurf55 is a component of different chromatin-modifying complexes, including the PRC2 (Polycomb repressive complex 2). Based on 1.75-Å crystal structure bound to histone H4 helix 1, we analyzed interactions (Nurf55 or p55 in fly and RbAp48/46 human) with N-terminal tail H3, first H4, an fragment subunit Su(z)12 using isothermal calorimetry pulldown experiments. Site-directed mutagenesis identified binding site H3 at top WD40 propeller. Unmodified K9me3- K27me3-containing peptides...
Receptor agonism remains poorly understood at the molecular and mechanistic level. In this study, we identified a fully human anti-Fas antibody that could efficiently trigger apoptosis therefore function as potent agonist. Protein engineering crystallography were used to mechanistically understand agonistic activity of antibody. The crystal structure complex was determined 1.9 Å resolution provided insights into epitope recognition comparisons with natural ligand FasL (Fas ligand). When...
Microfluidic technology has opened new possibilities for the crystallization of biological macromolecules during past decade. systems offer numerous advantages over conventional crystal growth methods. They enable easy handling nanovolumes solutions, extreme miniaturization, and parallelization assays, especially high-throughput screening applications. Our goal was to design a versatile, low cost, easy-to-use chip based on counter-diffusion that is compatible with on-chip crystallographic...
Coiled coils are well suited to drive subunit oligomerization and widely used in applications ranging from basic research medicine. The optimization of these requires a detailed understanding the molecular determinants that control coiled-coil formation. Although many have been identified characterized great detail, puzzling observation is their presence does not necessarily correlate with state given structure. Thus, other must play key role. To address this issue, we recently investigated...
Abstract Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe a novel androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA whole-exome sequencing the PDX organoids confirmed transcriptomic genomic similarity primary tumor. PNPCa harbours BRCA2 CHD1 somatic mutations, shows an SPOP/FOXA1 -like signature...
Poster SessionsC279 even greater frame rates if hardware binning is used.With this new mode of operation we are able to obtain ultra-fine sliced data (0.002º) on reasonable time scale (3º/min).This means that rocking curve evolution can be mapped with high resolution while cooling through a phase transition.Fine slicing also offers novel method for wavelength calibration by measuring many Friedel pairs from standard granular powder material, such as NIST LaB 6 .At the price smearing some...