Mathematical Virology: A new mathematical approach to viral evolution grounded in experiment
Lead Research Organisation:
University of Leeds
Department Name: Astbury Centre
Abstract
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Organisations
Publications
Twarock R
(2018)
A modelling paradigm for RNA virus assembly.
in Current opinion in virology
Geraets JA
(2015)
Asymmetric genome organization in an RNA virus revealed via graph-theoretical analysis of tomographic data.
in PLoS computational biology
Stockley PG
(2016)
Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid.
in Bacteriophage
Dykeman EC
(2013)
Building a viral capsid in the presence of genomic RNA.
in Physical review. E, Statistical, nonlinear, and soft matter physics
Rolfsson Ó
(2016)
Direct Evidence for Packaging Signal-Mediated Assembly of Bacteriophage MS2.
in Journal of molecular biology
Twarock R
(2018)
Hamiltonian path analysis of viral genomes.
in Nature communications
Patel N
(2017)
HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly.
in Nature microbiology
Stockley P
(2013)
Packaging signals in single-stranded RNA viruses: nature's alternative to a purely electrostatic assembly mechanism
in Journal of Biological Physics
Dykeman EC
(2013)
Packaging signals in two single-stranded RNA viruses imply a conserved assembly mechanism and geometry of the packaged genome.
in Journal of molecular biology
Patel N
(2015)
Revealing the density of encoded functions in a viral RNA.
in Proceedings of the National Academy of Sciences of the United States of America
| Description | We have demonstrated that RNA packaging signal-viral coat protein interactions in the family of positive sense single stranded RNA viruses can be novel drug targets. This group includes major human pathogens such as polio, HIV, hepatitis B etc. |
| Exploitation Route | In addition to teh previous patents filed by teh Universities of Leeds and York our work has now extended to the HBV virus and in a collabaortion with the NIH has led to a further patent application led by the NIH in which the Pi/co-I on nthis grant are named inventors. |
| Sectors | Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Our results have led to a new paradigm in virus assembly that has identified novel anti-viral drug targets, having implications for viral assembly and evolution. |
| First Year Of Impact | 2015 |
| Sector | Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Cultural |
| Description | New perspectives for anti-viral therapy: The regulatory roles of genomic RNA in virus assembly, infection and evolution. |
| Amount | £1,246,487 (GBP) |
| Funding ID | 110145 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2016 |
| End | 07/2021 |
| Description | • In situ Structural & Mechanistic Interrogation of dsDNA synthesis in Hepatitis B Virus |
| Amount | £291,000 (GBP) |
| Funding ID | MRF-044-0002-RG-PATEL |
| Organisation | Medical Research Council (MRC) |
| Department | Medical Research Foundation |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2018 |
| End | 04/2021 |
| Title | A novel anti-viral strategy against RNA viruses |
| Description | Our mathematical models resulted in the discovery of a new anti-viral strategy against single-stranded RNA viruses, including Hepatitis C and HIV. |
| IP Reference | GB1315785.4 |
| Protection | Patent application published |
| Year Protection Granted | |
| Licensed | Commercial In Confidence |
| Impact | This patent application initiated a cascade of subsequent applications al targeted at exploiting the novel aspect of virion assembly in ssRNA viruses we have discovered, namely RNA Packaging Signal-mediated Assembly. There are many aspects of this mechanism that are potentially exploitable, from directly-acting anti-virals targeting the RNA-CP contacts that drive the mechanism to recoding therapeutic RNAs as good assembly substrates for gene delivery and editing. |
| Title | METHODS OF TREATING HBV |
| Description | In collaboration with colleagues at the US NIH Frederick we screened for small molecule ligands that bind the major RNA RNA PS. We then characterised their affinities for the free RNA and assessed their ability to inhibit HBV replication in vivo (with the Dorner laboratory, Imperial College). On the basis of teh initial results our NIH colleagues filed this patent application for teh use of ligands based around their library as treatments for HBV infection. The in vivo data failed to be reproducible leading to abandonment of the patent since the ligand library used was fairly generic. |
| IP Reference | U.S. Application No. 62/685,145 |
| Protection | Patent application published |
| Year Protection Granted | |
| Licensed | No |
| Impact | We are in discussions to develop our understanding of the HBV virus to develop bespoke delivery systems for mRNAs. |
| Description | A conserved, self-assembly instruction manual for viral pathogens |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this seminar at the annual Astbury Centre for Structural Molecular Biology. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Life on the edge of equilibrium: The roles of asymmetric components in ssRNA viruses |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented this seminar to the Department of Virology & Infectious Disease at the University of Cambridge. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Living With Replicating Nanomachines: From Zika To The Common Cold |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Undergraduate students |
| Results and Impact | I gave this "after dinner" talk to the Cambridge Biological Society based at St Johns College Cambridge. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Nature's ssRNA Self-assembly Instruction Manual: Roles & Consequences of Packaging Signal-Mediated Assembly |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this seminar at the 25th Phage & Virus Assembly meeting in Turf Valley, USA. |
| Year(s) Of Engagement Activity | 2017 |
| Description | PS-mediated Assembly |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this talk jointly with my co-I on our Wellcome Trust Investigator Award, at an award holders symposium. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Reading the self-assembly instruction manuals of viruses: An enigmatic RNA function |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this seminar on the NIH Frederick campus. It was beamed to the Bethesda site but I have no idea of the size of that remote audience. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Seeing The "Invisible" Virus Assembly Instruction Manual In Action |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented this seminar (remotely) to the Brookhaven (USA) synchrotron user group. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Seeing is Believing: Revealing the Inner Workings of Viruses Using a Combination of Fluorescence, Electron Microscopy and X-rays |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Undergraduate students |
| Results and Impact | I gave this research seminar at Leeds Beckett University. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Simple RNA Viruses: Avoiding the Tyranny of Symmetry to Stay Infectious |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this seminar to the London School of Hygiene & Tropical Medicine. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Structural & functional investigations of a murderous viral enzyme in a native-like context |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I presented this seminar (remotely) to the 5th Summer School on Innovative Approaches for Identification of Antiviral Agents |
| Year(s) Of Engagement Activity | 2021 |
| Description | Therapeutic Exploitation of Essential RNA-Coat Protein Interactions in Viruses |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this research seminar to the "RNA Salon" meeting in Leeds. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Viral assembly 101: Yet more lessons for biology from a humble RNA phage |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this talk during a symposium held at the Institut Pasteur to celebrate the centenary of the discovery of phages. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Why Simple Viruses Get Frustrated. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this talk to the Astbury Centre annual symposium |
| Year(s) Of Engagement Activity | 2021 |
| Description | Why simple viruses get frustrated |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave this research seminar (remotely) to the Phage & Virus Assembly symposium organised by the University of York. |
| Year(s) Of Engagement Activity | 2021 |