A5089675833- Bacteriophages and microbial interactions
- Plant Virus Research Studies
- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- Algebraic structures and combinatorial models
- Quasicrystal Structures and Properties
- Viral Infections and Immunology Research
- Hepatitis B Virus Studies
- Animal Virus Infections Studies
- Advanced Topics in Algebra
- Monoclonal and Polyclonal Antibodies Research
- Evolution and Genetic Dynamics
- Nonlinear Waves and Solitons
- Hepatitis C virus research
- COVID-19 epidemiological studies
- Advanced biosensing and bioanalysis techniques
- Protein Structure and Dynamics
- Mathematical and Theoretical Epidemiology and Ecology Models
- RNA Research and Splicing
- Advanced Combinatorial Mathematics
- Mineralogy and Gemology Studies
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- Respiratory viral infections research
- Plant and Fungal Interactions Research
University of York
2016-2025
Polytechnic University of Turin
2022
University of Leeds
2021
University of the Basque Country
2011
International Centre for Mathematical Sciences
2008
City, University of London
2002-2005
Mathematical Institute of the Slovak Academy of Sciences
2005
Northampton Community College
2004
Isaac Newton Institute for Mathematical Sciences
2004
Clausthal University of Technology
1997-2000
This paper is devoted to the multidisciplinary modelling of a pandemic initiated by an aggressive virus, specifically so-called SARS-CoV-2 Severe Acute Respiratory Syndrome, corona virus n.2. The study developed within multiscale framework accounting for interaction different spatial scales, from small scale itself and cells, large individuals further up collective behaviour populations. An interdisciplinary vision thanks contributions epidemiologists, immunologists economists as well those...
Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. Although computational methods for designing novel self-assembling proteins advanced substantially over the past decade, they primarily focus on static structures. Here we characterize three distinct computationally designed exhibit unanticipated structural diversity arising from flexibility in their subunits. Cryo-EM single-particle reconstructions and native mass...
Significance One of the important puzzles in virology is how viruses assemble protective protein containers for their genomes rapidly and efficiently during an infection. Recent advances field RNA suggests that multiple specific contacts between genomic proteins these play crucial roles this process, but detailed molecular mechanisms by which occurs are largely obscure. We describe here a mathematical model virus assembly incorporates other details real infections. It demonstrates such act...
Using cross-linking coupled to matrix-assisted laser desorption/ionization mass spectrometry and CLIP-Seq sequencing, we determined the peptide oligonucleotide sequences at interfaces between capsid proteins genomic RNA of bacteriophage MS2. The results suggest that same coat protein (CP)–RNA maturation (MP)–RNA are used in every viral particle. portions contact with CP subunits span genome, consistent a large number discrete similar contacts within each Many these sites match previous...
Abstract Viruses have evolved protein containers with a wide spectrum of icosahedral architectures to protect their genetic material. The geometric constraints defining these container designs, and implications for viral evolution, are open problems in virology. principle quasi-equivalence is currently used predict virus architecture, but improved imaging techniques revealed increasing numbers outliers. We show that this theory special case an overarching design icosahedral, as well...
Revolution in an RNA-packaging capsid Artificial nucleocapsid proteins, which could be analogous to those used by viruses package their genomes, are a promising way protect and deliver RNAs. Using escalating challenge nucleases, Tetter et al. evolved protein that forms multimeric, spherical cages into highly efficient selectively packages its own encoding RNA. Cryo–electron microscopy of the final design intermediates revealed stepwise expansion size, enabled destabilizing amino acid...
The formation of a protective protein container is an essential step in the life-cycle most viruses. In case single-stranded (ss)RNA viruses, this occurs parallel with genome packaging co-assembly process. Previously, it had been thought that process can be explained entirely by electrostatics. Inspired recent single-molecule fluorescence experiments recapitulate RNA specificity seen vivo for two model we present alternative theory, which recognizes important cooperative roles played...
Assembly of the major viral pathogens Picornaviridae family is poorly understood. Human parechovirus 1 an example such viruses that contains 60 short regions ordered RNA density making identical contacts with protein shell. We show here via a combination RNA-based systematic evolution ligands by exponential enrichment, bioinformatics analysis and reverse genetics these segments are bound to coat proteins in sequence-specific manner. Disruption either recognition motif or its contact amino...
Significance Single-stranded RNA viruses self-assemble protective protein containers around their cognate genomes rapidly and efficiently at low concentrations. encapsidation in vivo occurs preferentially with the genome, contrast to many vitro reassembly experiments. We describe molecular detail how this specificity efficiency is accomplished using multiple contacts between coat proteins dispersed packaging signals viral genome. The sequences relative positioning of are important for...
Five structural domains in chain A and partial charge distribution RBD with same orientation as of A.
Virus-like particles (VLPs) have significant potential as artificial vaccines and drug delivery systems. The ability to control their size has wide ranging utility but achieving such controlled polymorphism using a single protein subunit is challenging it requires altering VLP geometry. Here we achieve of MS2 bacteriophage VLPs via insertion amino acid sequences in an external loop shift morphology significantly larger forms. resulting geometry by the length type insert. Cryo electron...
Significance Viruses composed of a shell coat proteins enclosing ssRNA genomes are among the simplest biological entities. Their lifecycles include range processes, such as specific genome encapsidation and efficient capsid self-assembly. Until recently, these were not linked, but we have shown that many viruses in this class encode multiple, degenerate RNA sequence/structure motifs bind cognate collectively. This simultaneously ensures packaging virion assembly via an RNA-encoded...
Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing development anti-viral strategies targeting this essential part life cycle. We report identification, via RNA SELEX and bioinformatics, multiple sites across genome a typical enterovirus, enterovirus-E (EV-E), that each have affinity for cognate capsid protein (CP) capsomer. Many these evolutionarily conserved known EV-E...
Protein capsids are a widespread form of compartmentalization in nature. Icosahedral symmetry is ubiquitous derived from spherical viruses, as this geometry maximizes the internal volume that can be enclosed within. Despite strong preference for icosahedral symmetry, we show simple point mutations virus-like capsid drive assembly unique symmetry-reduced structures. Starting with encapsulin Myxococcus xanthus , 180-mer bacterial adopts well-studied viral HK97 fold, use mass photometry and...
Hollow proteinaceous particles are useful nanometric containers for delivery and catalysis. Understanding the molecular mechanisms geometrical theory behind polymorphic protein assemblies provides a basis designing ones with desired morphology. As such, we found that circularly permuted variant of cage-forming enzyme, Aquifex aeolicus lumazine synthase, cpAaLS, assembles into variety hollow spherical cylindrical structures in response to changes ionic strength. Cryogenic electron microscopy...