A5015069689- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Genetic Associations and Epidemiology
- Bacteriophages and microbial interactions
- Genomics and Rare Diseases
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Animal Disease Management and Epidemiology
- RNA Research and Splicing
- Diet and metabolism studies
- Vector-Borne Animal Diseases
- Genomics and Chromatin Dynamics
- Viral gastroenteritis research and epidemiology
- Microbial metabolism and enzyme function
- Microbial Metabolic Engineering and Bioproduction
- Biochemical Acid Research Studies
- CRISPR and Genetic Engineering
- Bioinformatics and Genomic Networks
- T-cell and Retrovirus Studies
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Telomeres, Telomerase, and Senescence
- Cellular Mechanics and Interactions
AstraZeneca (United Kingdom)
2022-2025
AstraZeneca (Brazil)
2022-2024
Discovery Centre
2024
Institute of Structural and Molecular Biology
2018-2024
University College London
2018-2024
University of Virginia
2018-2019
University of Warsaw
2016-2018
International Institute of Molecular and Cell Biology
2013-2017
Heidelberg University
2014
This paper is a report of second round RNA-Puzzles, collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, 10, represented sequences three large structures with limited or no homology previously solved molecules. A lariat-capping ribozyme, as well riboswitches complexed to adenosylcobalamin tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, AMBER refinement. Some derived models...
Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers discover drug targets1-4. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to plasma proteome remains largely unknown. Here we associations between protein-coding 2,923 protein abundances measured in 49,736 UK Biobank individuals. Our variant-level exome-wide study identified 5,433...
African swine fever virus (ASFV) causes incurable and often lethal hemorrhagic in domestic pigs. In 2020, ASF presents an acute global animal health emergency that has the potential to devastate entire national economies as effective vaccines or antiviral drugs are not currently available (according Food Agriculture Organization of United Nations). With major outbreaks ongoing Eastern Europe Asia, urgent action is needed advance our knowledge about fundamental biology ASFV, including...
PIN-like domains constitute a widespread superfamily of nucleases, diverse in terms the reaction mechanism, substrate specificity, biological function and taxonomic distribution. Proteins with are involved central cellular processes, such as DNA replication repair, mRNA degradation, transcription regulation ncRNA maturation. In this work, we identify classify most complete set to provide first comprehensive analysis sequence-structure-function relationships within whole PIN domain-like...
African swine fever virus (ASFV) has a major global economic impact. With case fatality in domestic pigs approaching 100%, it currently presents the largest threat to animal farming. Although genomic differences between attenuated and highly virulent ASFV strains have been identified, molecular determinants for virulence at level of gene expression remained opaque. Here, we characterize transcriptome genotype II Georgia 2007/1 (GRG) during infection physiologically relevant host cells,...
Telomeres protect chromosome ends from damage and their length is linked with human disease aging. We developed a joint telomere metric, combining quantitative PCR whole-genome sequencing measurements 462,666 UK Biobank participants. This metric increased SNP heritability, suggesting that it better captures genetic regulation of length. Exome-wide rare-variant gene-level collapsing association studies identified 64 variants 30 genes significantly associated length, including allelic series...
Coagulase negative staphylococci (CoNS) are commensal bacteria on human skin. Staphylococcus lugdunensis is a unique CoNS which produces various virulence factors and may, like S. aureus, cause severe infections, particularly in hospital settings. Unlike other staphylococci, it remains highly susceptible to antimicrobials, genome-based phylogenetic studies have evidenced conserved genome that distinguishes from all staphylococci. We demonstrate possesses closed pan-genome with very limited...
Abstract In eukaryotes, histone paralogues form obligate heterodimers such as H3/H4 and H2A/H2B that assemble into octameric nucleosome particles. Archaeal histones are dimeric on DNA ‘hypernucleosome’ particles of varying sizes with each dimer wrapping 30 bp DNA. These composed canonical variant paralogues, but the function these variants is poorly understood. Here, we characterise structure paralogue MJ1647 from Methanocaldococcus jannaschii has a unique C-terminal extension enabling...
Genomics can provide insight into the etiology of type 2 diabetes and its comorbidities, but assigning functionality to non-coding variants remains challenging. Polygenic scores, which aggregate variant effects, uncover mechanisms when paired with molecular data. Here, we test polygenic scores for cardiometabolic comorbidities associations 2,922 circulating proteins in UK Biobank. The genome-wide score associates 617 proteins, 75% also associate another score. Partitioned capture distinct...
Abstract The unprecedented scale of genomic databases has revolutionized our ability to identify regions in the human genome intolerant variation—regions often implicated disease. However, these datasets remain constrained by limited ancestral diversity. Here, we analyze whole-exome sequencing data from 460,551 UK Biobank and 125,748 Genome Aggregation Database (gnomAD) participants across multiple ancestries test several key intolerance metrics, including Residual Variance Intolerance Score...
Abstract Recruitment of RNA polymerase and initiation factors to the promoter is only known target for transcription activation repression in archaea. Whether any subsequent steps towards productive elongation are involved regulation not known. We characterised how basal machinery distributed along genes archaeon Saccharolobus solfataricus . discovered a distinct early phase where polymerases sequentially recruit Spt4/5 Elf1 form complex (TEC) before TEC escapes into transcription. escape...
The His-Me finger endonucleases, also known as HNH or ββα-metal form a large and diverse protein superfamily. domain can be found in proteins that play an essential role cells, including genome maintenance, intron homing, host defense target offense. Its overall structural compactness non-specificity make it perfectly-tailored pathogenic module participates on both sides of inter- intra-organismal competition. An extremely low sequence similarity across the superfamily makes difficult to...
The archaeal RNA polymerase (RNAP) is a double-psi β-barrel enzyme closely related to eukaryotic RNAPII in terms of subunit composition and architecture, promoter elements basal transcription factors required for the initiation elongation phase transcription. Understanding is, therefore, key delineate universally conserved fundamental mechanisms as well evolution archaeo-eukaryotic machineries. dynamic interplay between RNAP subunits, nucleic acids dictates activity ultimately gene...
α2β1 integrin is one of the most important collagen-binding receptors and has been implicated in numerous widely spread thrombotic immune diseases. a potent tumour suppressor its downregulation associated with increased metastasis poor prognosis breast cancer. Currently, very little known about mechanism regulating cell surface expression trafficking. Here, using quantitative fluorescent microscopy-based RNAi assay, we investigated impact 386 cytoskeleton-associated or regulatory genes on...
The family of D-isomer specific 2-hydroxyacid dehydrogenases (2HADHs) contains a wide range oxidoreductases with various metabolic roles as well biotechnological applications. Despite vast amount biochemical and structural data for representatives the family, long complex evolution broad sequence diversity hinder functional annotations uncharacterized members. We report an in-depth phylogenetic analysis, followed by mapping available on reconstructed tree. analysis suggests that some...
Abstract Combining human genomics with proteomics is becoming a powerful tool for drug discovery. Associations between genetic variants and protein levels can uncover disease mechanisms, clinical biomarkers, candidate targets. To date, most population-level proteogenomic studies have focused on common alleles through genome-wide association (GWAS). Here, we studied the contribution of rare protein-coding to 1,472 plasma proteins abundances measured via Olink Explore 1536 assay in 50,829 UK...
Prokaryotic ribosomal protein genes are typically grouped within highly conserved operons. In many cases, one or more of the encoded proteins not only bind to a specific site in RNA, but also motif localized their own mRNA, and thereby regulate expression operon. this study, we computationally predicted an RNA present bacterial phyla 5′ untranslated region operons encoding S6 S18. We demonstrated that S6:S18 complex binds motif, which hereafter refer as complex-binding (S6S18CBM). This is...
Abstract RNA polymerase inhibition plays an important role in the regulation of transcription response to environmental changes and virus-host relationship. Here we present high-resolution structures two such RNAP-inhibitor complexes that provide structural bases underlying RNAP archaea. The Acidianus two-tailed virus encodes RIP factor binds inside DNA-binding channel RNAP, inhibiting by occlusion binding sites for nucleic acid initiation TFB. Infection with Sulfolobus Turreted Icosahedral...
The d-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers and duplications losses. As result, the exact functional annotation of individual members can be extrapolated to very limited extent. Here, we revise previous simplified view on classification 2HADH family; specifically, show that previously delineated glyoxylate/hydroxypyruvate reductase (GHPR) subfamily consists two separated GHRA GHRB subfamilies. We compare...
The genomes of intracellular symbiotic or pathogenic bacteria, such as Buchnera, Mycoplasma, and Rickettsia, are typically smaller compared with their free-living counterparts. Here we showed that noncoding RNA (ncRNA) families, which conserved in frequently could not be detected by computational methods the small genomes. Statistical tests demonstrated absence is an artifact low GC content deletions these genomes, thus it was indicative independent loss ncRNAs different endosymbiotic...
RNA has been found to play an ever-increasing role in a variety of biological processes. The function most non-coding molecules depends on their structure. Comparing and classifying macromolecular 3D structures is crucial importance for structure-based inference it used the characterization functional motifs structure prediction by comparative modeling. However, compared numerous methods protein superposition, there are few tools dedicated superimposing structures. Here, we present...