ORCID Profile
0000-0002-6982-4660
Current Organisations
Royal Netherlands Meteorological Institute
,
University of Oxford
,
Delft University of Technology
,
European Bioinformatics Institute
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Publisher: Springer Science and Business Media LLC
Date: 05-2002
DOI: 10.1038/417141A
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2011
DOI: 10.1261/RNA.2750811
Abstract: During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor.
Publisher: Oxford University Press (OUP)
Date: 2006
DOI: 10.1093/NAR/GKJ149
Publisher: Springer Science and Business Media LLC
Date: 15-02-2001
DOI: 10.1038/35057062
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Publisher: Springer Science and Business Media LLC
Date: 11-2022
DOI: 10.1038/S41594-022-00849-W
Abstract: Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements the impact of missense variants function and ligand binding site predictions modeling of interactions and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across erse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.
Publisher: Oxford University Press (OUP)
Date: 2004
DOI: 10.1093/NAR/GKH121
Publisher: Oxford University Press (OUP)
Date: 18-11-2010
DOI: 10.1093/NAR/GKQ1173
Publisher: Rockefeller University Press
Date: 28-03-2017
DOI: 10.1084/JEM.20161382
Abstract: The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phox and p22phox. Consequently, Eros-deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.
Publisher: Oxford University Press (OUP)
Date: 06-03-2013
DOI: 10.1093/NAR/GKT148
Publisher: American Society for Microbiology
Date: 25-08-2020
Abstract: Acyltransferase-3 (AT3) domain-containing membrane proteins are involved in O -acetylation of a erse range of carbohydrates across all domains of life. In bacteria they are essential in processes including symbiosis, resistance to antimicrobials, and biosynthesis of antibiotics. Their mechanism of action, however, is poorly characterized. We analyzed two acetyltransferases as models for this important family of membrane proteins, which modify carbohydrates on the surface of the pathogen Salmonella enterica , affecting immunogenicity, virulence, and bacteriophage resistance. We show that when these AT3 domains are fused to a periplasmic partner domain, both domains are required for substrate acetylation. The data show conserved elements in the AT3 domain and unique structural features of the periplasmic domain. Our data provide a working model to probe the mechanism and function of the erse and important members of the widespread AT3 protein family, which are required for biologically significant modifications of cell-surface carbohydrates.
Publisher: Oxford University Press (OUP)
Date: 05-11-2018
DOI: 10.1093/NAR/GKY1034
Publisher: Public Library of Science (PLoS)
Date: 20-09-2021
Publisher: Cold Spring Harbor Laboratory
Date: 24-12-2020
DOI: 10.1101/2020.12.24.424174
Abstract: Changes at the cell surface enable bacteria to survive in dynamic environments, such as erse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure thus variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly-available long-read genome sequencing data, we propose this new class could contain over 50 distinct proteins, including those implicated in host colonisation and biofilm formation by human pathogens. In large multi-domain proteins, sequence ergence between adjacent domains appears to reduce inter-domain misfolding. Periscope Proteins break this “rule”, suggesting their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria and the immune system.
Publisher: Oxford University Press (OUP)
Date: 08-12-2018
DOI: 10.1093/NAR/GKY1206
Publisher: Public Library of Science (PLoS)
Date: 19-09-2013
Publisher: Public Library of Science (PLoS)
Date: 03-06-2008
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/543179A
Publisher: Proceedings of the National Academy of Sciences
Date: 09-12-2019
Abstract: Streptococcus groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the structure of the Rib domain was previously unknown. Structures of single Rib domains of differing length reveal a rare case of domain atrophy through deletion of 2 core antiparallel strands, resulting in the loss of an entire sheet of the β-sandwich from an immunoglobulin-like fold. Previously, observed variation in the number of Rib domains within these bacterial cell wall-attached proteins has been suggested as a mechanism of immune evasion. Here, the structure of tandem domains, combined with molecular dynamics simulations and small angle X-ray scattering, suggests that variability in Rib domain number would result in differential projection of an N-terminal host-colonization domain from the bacterial surface. The identification of 2 further structures where the typical B-D-E immunoglobulin β-sheet is replaced with an α-helix further confirms the extensive structural malleability of the Rib domain.
Publisher: Proceedings of the National Academy of Sciences
Date: 31-03-2003
Abstract: Most modern speech recognition uses probabilistic models to interpret a sequence of sounds. Hidden Markov models, in particular, are used to recognize words. The same techniques have been adapted to find domains in protein sequences of amino acids. To increase word accuracy in speech recognition, language models are used to capture the information that certain word combinations are more likely than others, thus improving detection based on context. However, to date, these context techniques have not been applied to protein domain discovery. Here we show that the application of statistical language modeling methods can significantly enhance domain recognition in protein sequences. As an ex le, we discover an unannotated Tf_Otx Pfam domain on the cone rod homeobox protein, which suggests a possible mechanism for how the V242M mutation on this protein causes cone-rod dystrophy.
Publisher: Proceedings of the National Academy of Sciences
Date: 31-05-2021
Abstract: The structure of single and tandem SHIRT domains from the streptococcal surface protein Sgo_0707 were determined. In conjunction with biophysics and molecular dynamics simulations, the results show that the observed gene length variation would result in differential projection of the host ligand binding domain on the bacterial cell surface. An analysis of long-read DNA sequence data reveals many other repetitive bacterial surface proteins that appear to undergo gene length variation. We propose that these variable-length “Periscope Proteins” represent an important mechanism of bacterial cell surface modification with potential roles in infection and immune evasion.
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Oxford University Press (OUP)
Date: 29-07-2023
Abstract: NASA is engaged in planning for a Habitable Worlds Observatory (HabWorlds ), a coronagraphic space mission to detect rocky planets in habitable zones and establish their habitability. Surface liquid water is central to the definition of planetary habitability. Photometric and polarimetric phase curves of starlight reflected by an exoplanet can reveal ocean glint, rainbows, and other phenomena caused by scattering by clouds or atmospheric gas. Direct imaging missions are optimized for planets near quadrature, but HabWorlds ’ coronagraph may obscure the phase angles where such optical features are strongest. The range of accessible phase angles for a given exoplanet will depend on the planet’s orbital inclination and/or the coronagraph’s inner working angle (IWA). We use a recently created catalog relevant to HabWorlds of 164 stars to estimate the number of exo-Earths that could be searched for ocean glint, rainbows, and polarization effects due to Rayleigh scattering. We find that the polarimetric Rayleigh scattering peak is accessible in most of the exo-Earth planetary systems. The rainbow due to water clouds at phase angles of ∼20○ − 60○ would be accessible with HabWorlds for a planet with an Earth equivalent instellation in ∼46 systems, while the ocean glint signature at phase angles of ∼130○ − 170○ would be accessible in ∼16 systems, assuming an IWA = 62 mas (3λ/D). Improving the IWA = 41 mas (2λ/D) increases accessibility to rainbows and glints by factors of approximately 2 and 3, respectively. By observing these scattering features, HabWorlds could detect a surface ocean and water cycle, key indicators of habitability.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alex Bateman.