A5038655916- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Enzyme Structure and Function
- Mast cells and histamine
- Cerebrovascular and genetic disorders
- Atherosclerosis and Cardiovascular Diseases
- Plant Disease Resistance and Genetics
- Galectins and Cancer Biology
- Biomedical and Engineering Education
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- interferon and immune responses
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Innovation, Sustainability, Human-Machine Systems
- Signaling Pathways in Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Alzheimer's disease research and treatments
- Genomics and Phylogenetic Studies
- Endoplasmic Reticulum Stress and Disease
- Lipoproteins and Cardiovascular Health
- Vanadium and Halogenation Chemistry
- Protease and Inhibitor Mechanisms
- Nuclear Structure and Function
ETH Zurich
2014-2023
University of California, San Francisco
2022
University of Zurich
2017-2022
The recent devastating pandemic has drastically reminded humanity of the importance constant scientific and technological progress. A strong interdisciplinary dialogue between academic industrial scientists various specialties, entrepreneurs, managers public is paramount in triggering new breakthrough ideas which often emerge at interface disciplines. following sections, compiled by a highly diverse group authors, are summarizing recently achieved game-changing leaps science technology....
The locus of the human proprotein convertase subtilisin-kexin type-7 (PC7) gene (PCSK7) is on chromosome 11q23.3 close to cluster APOA5/APOA4/APOC3/APOA1, a region implicated in regulation lipoprotein metabolism. A GWAS reported association PCSK7 SNPs with plasma triglyceride (TG), and exome sequencing African Americans revealed low-frequency coding variant PC7 (R504H; SNP rs142953140) ~ 30% TG reduction. Another rs508487 linkage disequilibrium promoter liver-derived apolipoprotein A-V...
Abstract Productive ribosomal RNA (rRNA) compaction during ribosome assembly necessitates establishing correct tertiary contacts between distant secondary structure elements. Here, we quantify the response of yeast proteome to low temperature (LT), a condition where aberrant mis-paired folding intermediates accumulate. We show that, at LT, cells globally boost production their machinery. find that LT-induced factor, Puf6, binds nascent catalytic RNA-rich subunit interface within 60S...
Abstract Apolipoprotein L1 (ApoL1) is a circulating innate immunity protein protecting against trypanosome infection. However, two ApoL1 coding variants are associated with highly increased risk of chronic kidney disease. Here we present X-ray and NMR structures the N-terminal domain (NTD) its closest relative ApoL2. In both proteins, four five NTD helices form four-helix core structure which different from classical bundle pore-forming colicin A. The reactivity conformation-specific...
The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) seems to extend the RNA-binding surface six nucleotides for SF1 (Homo sapiens) and seven GLD-1 (Caenorhabditis elegans). To understand structural basis of this probable difference specificity, we determined solution structure KH-QUA2 complete consensus sequence identified tra-2 gene. Compared SF1,...
Abstract Vascular leakage, or edema, is a serious complication of acute allergic reactions. leakage triggered by the release histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression Neutrophil Serine Protease 4 (NSP4) during early stages cell development regulates cell-mediated vascular leakage. In myeloid precursors, granulocyte–macrophage progenitors (GMPs), loss NSP4 results in decrease cellular levels histamine, heparin/heparan sulfate. Mast...
Construction of the eukaryotic ribosome is a complex process in which nascent ribosomal RNA (rRNA) emerging from Polymerase I hierarchically folds into native three-dimensional structure. Modular assembly individual domains through interactions with proteins and myriad factors permit efficient disentanglement error-prone folding process. Following these dynamic events, long-range tertiary are orchestrated to compact rRNA. A combination genetic, biochemical, structural studies now providing...
Abstract The trimeric serine protease HTRA1 is a genetic risk factor associated with geographic atrophy (GA), currently untreatable form of age-related macular degeneration. Here, we describe the allosteric inhibition mechanism by clinical Fab fragment, being evaluated for GA treatment. Using cryo-EM, X-ray crystallography and biochemical assays identify exposed LoopA as sole epitope, which approximately 30 Å away from active site. cryo-EM structure HTRA1:Fab complex in combination molecular...
Abstract Final maturation of eukaryotic ribosomes occurs in the cytoplasm and requires sequential removal associated assembly factors processing immature 20S pre-RNA. Using cryo-electron microscopy (cryo-EM), we have determined structure a cytoplasmic pre-40S particle poised to initiate final at resolution 3.4 Å. The reveals extent conformational rearrangements 3’ major minor domains ribosomal RNA that take place during maturation, as well roles Enp1, Ltv1, Rio2, Tsr1, Pno1 process....
Abstract The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by Recognition Motifs (RRM1 & RRM2) during reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover consensus sequence bound each RRM. High-resolution NMR structures show that RRM2 recognizes 5´-GNGG-3´ motif leading an unusual mille-feuille topology. These also reveal how RRM1 preferentially interacts with CC-dinucleotide upstream this...
ABSTRACT The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by Recognition Motifs (RRM1 & RRM2) during reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover consensus sequence bound each RRM. High-resolution NMR structures show that RRM2 recognizes 5’-GNGG-3’ motif leading an unusual mille-feuille topology. These also reveal how RRM1 preferentially interacts with CC-dinucleotide upstream this...
Abstract The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by Recognition Motifs (RRM1 & RRM2) during reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover consensus sequence bound each RRM. High-resolution NMR structures show that RRM2 recognizes 5´-GNGG-3´ motif leading an unusual mille-feuille topology. These also reveal how RRM1 preferentially interacts with CC-dinucleotide upstream this...