Replication of influenza virus at the molecular level
Lead Research Organisation:
University of Oxford
Department Name: Sir William Dunn Sch of Pathology
Abstract
The fundamental aim of this proposed research programme is to develop a much deeper understanding of the molecular and cell biology of influenza viruses, allowing the development of novel strategies to combat influenza. Influenza viruses are a major contributor to disease and death in humans, and with their ability to cause yearly epidemics and occasional pandemics they represent a considerable burden to healthcare systems globally. The most devastating influenza pandemic, the 1918 "Spanish" flu, caused over 50 million deaths worldwide. Wild birds represent an important reservoir for influenza A viruses from which novel pandemic strains can emerge. Currently the H5N1, H7N7 and H9N2 subtypes are considered the biggest threats as these are prevalent in birds and can infect humans directly. Although these viruses lack the ability to transmit between humans, they can cause severe disease and death. The concern is that these viruses, through adaptation or by mixing with other virus subtypes, could gain the ability to easily transmit between humans and lead to a new pandemic. Although vaccines against seasonal influenza and a very limited number of antiviral drugs are available, we are surprisingly defenceless against emerging pandemic influenza viruses. To prepare a vaccine matching a pandemic strain could take several months and resistance to drugs is an increasing problem. Therefore novel strategies for the control of influenza need to be developed.
The focus of the proposed research programme is the transcriptional machinery of influenza virus, a complex of several proteins which is responsible for copying the genetic information of the virus in a host cell. The genetic information of influenza virus is stored in segments of RNA. These need to be copied into messenger RNA (transcription) to be translated into viral proteins, as well as replicated to produce new copies of the genome. These new copies are then assembled with viral proteins to be incorporated into new virus particles that are released from the host cell to initiate new cycles of viral reproduction. Interestingly, transcriptional machineries of influenza viruses that infect birds tend to work poorly in human cells. When "bird flu" transmits to humans the machinery usually undergoes changes to become adapted to its new host. In other words, the transcriptional machinery of an influenza virus can determine which host the virus could infect, and can also determine the severity and the outcome of the disease caused.
Although the viral transcriptional machinery performs essential functions in a host cell-specific manner without which the virus cannot survive, we do not understand how this machine works at the molecular level or how the host cell's species (whether bird or human) affects its function. We therefore wish to determine the molecular mechanisms used by the viral transcriptional machinery to transcribe and replicate the viral genome, and the molecular interactions between the viral transcriptional machinery and the host cell. This research programme will help to understand the molecular basis of virulence, host range restriction and adaptation of influenza viruses to new hosts. It will therefore allow a better understanding of the emergence of strains with pandemic potential. Importantly, it will underpin the development of novel antiviral strategies by indentifying targets for antiviral drugs in the viral transcriptional machinery as well as in cellular proteins. It could also facilitate the development of novel influenza vaccines, offering protection against a wide variety of influenza virus strains. Any emerging information during the course of the programme will be exploited, potentially with the involvement of industrial partners.
The focus of the proposed research programme is the transcriptional machinery of influenza virus, a complex of several proteins which is responsible for copying the genetic information of the virus in a host cell. The genetic information of influenza virus is stored in segments of RNA. These need to be copied into messenger RNA (transcription) to be translated into viral proteins, as well as replicated to produce new copies of the genome. These new copies are then assembled with viral proteins to be incorporated into new virus particles that are released from the host cell to initiate new cycles of viral reproduction. Interestingly, transcriptional machineries of influenza viruses that infect birds tend to work poorly in human cells. When "bird flu" transmits to humans the machinery usually undergoes changes to become adapted to its new host. In other words, the transcriptional machinery of an influenza virus can determine which host the virus could infect, and can also determine the severity and the outcome of the disease caused.
Although the viral transcriptional machinery performs essential functions in a host cell-specific manner without which the virus cannot survive, we do not understand how this machine works at the molecular level or how the host cell's species (whether bird or human) affects its function. We therefore wish to determine the molecular mechanisms used by the viral transcriptional machinery to transcribe and replicate the viral genome, and the molecular interactions between the viral transcriptional machinery and the host cell. This research programme will help to understand the molecular basis of virulence, host range restriction and adaptation of influenza viruses to new hosts. It will therefore allow a better understanding of the emergence of strains with pandemic potential. Importantly, it will underpin the development of novel antiviral strategies by indentifying targets for antiviral drugs in the viral transcriptional machinery as well as in cellular proteins. It could also facilitate the development of novel influenza vaccines, offering protection against a wide variety of influenza virus strains. Any emerging information during the course of the programme will be exploited, potentially with the involvement of industrial partners.
Technical Summary
The proposed research programme aims to uncover fundamental aspects of structure and function of influenza virus as well as virus-host interactions and host responses to viral infection. The main focus is the viral transcriptional machinery, a multi-subunit enzyme complex, which transcribes and replicates the viral RNA genome in a host cell-dependent manner. This enzyme, which consists of the viral RNA polymerase and nucleoprotein, is essential for the virus to replicate and is an important determinant of host range and virulence. The research objectives are to determine the molecular mechanisms of transcription and replication of the viral RNA genome by this transcriptional machinery, to identify and characterise the molecular interactions it makes with the host cell, and to determine the implications of these interactions for cell tropism, host range and virulence. The proposal builds on the achievements of my research over a 20 year period, in the last 10 years supported by a Senior Research Fellowship and 5-year Research Grant from the MRC. We will use the latest state-of-the-art technologies in single-molecule imaging (FRET), super-resolution microscopy (PALM and STORM), structural biology and proteomics in combination with methods from biochemistry, cell biology and virology. Recombinant proteins for structural analysis will be expressed using recombinant baculovirus technology (Multi-Bac) allowing the expression of multiple proteins from a single baculovirus in insect cells. Influenza virus mutants for cell biology and animal studies will be generated by reverse genetics. Virulence studies will use established animal models for influenza. Impacts of this research will include understanding the emergence of influenza strains with pandemic potential, discovery of novel viral and cellular drug targets, and the development of novel vaccines by reverse genetics. Promising avenues will be exploited in collaboration with industrial partners.
Planned Impact
The proposed research programme focuses on fundamental aspects of structure and function of influenza viruses as well as on virus-host interactions and host responses to viral infection. Influenza viruses are a major contributor to disease and death in humans, and with their ability to cause yearly epidemics and occasional pandemics they represent a considerable burden to healthcare systems globally. It is estimated that influenza is responsible for between 3 million and 5 million cases of severe illness and between 250,000 and 500,000 deaths worldwide annually. Influenza could be considered one of today's biggest threats to the world's socio-economic health, and the threat of a novel pandemic influenza virus emerging in the human population against which there would be no pre-existing immunity remains a cause for serious concern. The UK National Security Council in its Strategic Defence Review (published on 18 October 2010) classified a potential influenza pandemic in the group of risks of the highest priority for UK national security.
In the shorter term (year 2-3 of the programme), the research programme will uncover molecular mechanisms used by influenza viruses to adapt to a new host and it will therefore be useful in identifying influenza viruses with the potential to cause a pandemic. This knowledge could contribute towards evidence-based policy making and influence public policies on influenza pandemic preparedness.
In the longer term (beyond 5 years), the research programme has the potential to impact the public by underpinning the development of antiviral drugs and improved vaccines. Novel drugs and vaccines could contribute to the reduction of disease and human suffering, benefit health services through a reduction in bed residence and associated nursing and treatment costs and the economy through reduced absence from work, and in the case of an emerging pandemic they might avert a global disaster. This long-term aim will be fully exploited with the involvement of new collaborators, specialists in structure-based drug design and vaccine development as well as industrial partners depending on the outcomes of research.
Any outcomes with potential of being commercially exploited will be communicated to Isis Innovation Limited, a wholly-owned subsidiary of the University of Oxford, managing technology transfer and academic consulting for scientists working at the University of Oxford. The project also has the potential to contribute to wealth creation and economic prosperity through the creation and growth of companies and jobs, enhancing business revenue and innovative capacity. This could be achieved by the commercialisation and exploitation of scientific knowledge, leading to spin-off companies and the creation of new drugs and vaccines.
The project will also contribute to training and delivering highly skilled researchers. PDRAs employed on the project will gain skills in virology as well as in novel emerging technologies (e.g. single-molecule technologies, super-resolution microscopy, proteomics) that will allow them to take leading positions in various fields of industry, e.g. in drug and vaccine development not only against influenza virus, but also against other significant human and animal pathogens.
Scientists employed on the project will participate in public outreach activities contributing to increasing public awareness and understanding of the latest developments in influenza virus research, for example by giving public talks and participating in the annual Oxford Science Festival. We will take every opportunity to communicate our research to schoolchildren to increase interest in natural sciences.
In the shorter term (year 2-3 of the programme), the research programme will uncover molecular mechanisms used by influenza viruses to adapt to a new host and it will therefore be useful in identifying influenza viruses with the potential to cause a pandemic. This knowledge could contribute towards evidence-based policy making and influence public policies on influenza pandemic preparedness.
In the longer term (beyond 5 years), the research programme has the potential to impact the public by underpinning the development of antiviral drugs and improved vaccines. Novel drugs and vaccines could contribute to the reduction of disease and human suffering, benefit health services through a reduction in bed residence and associated nursing and treatment costs and the economy through reduced absence from work, and in the case of an emerging pandemic they might avert a global disaster. This long-term aim will be fully exploited with the involvement of new collaborators, specialists in structure-based drug design and vaccine development as well as industrial partners depending on the outcomes of research.
Any outcomes with potential of being commercially exploited will be communicated to Isis Innovation Limited, a wholly-owned subsidiary of the University of Oxford, managing technology transfer and academic consulting for scientists working at the University of Oxford. The project also has the potential to contribute to wealth creation and economic prosperity through the creation and growth of companies and jobs, enhancing business revenue and innovative capacity. This could be achieved by the commercialisation and exploitation of scientific knowledge, leading to spin-off companies and the creation of new drugs and vaccines.
The project will also contribute to training and delivering highly skilled researchers. PDRAs employed on the project will gain skills in virology as well as in novel emerging technologies (e.g. single-molecule technologies, super-resolution microscopy, proteomics) that will allow them to take leading positions in various fields of industry, e.g. in drug and vaccine development not only against influenza virus, but also against other significant human and animal pathogens.
Scientists employed on the project will participate in public outreach activities contributing to increasing public awareness and understanding of the latest developments in influenza virus research, for example by giving public talks and participating in the annual Oxford Science Festival. We will take every opportunity to communicate our research to schoolchildren to increase interest in natural sciences.
Publications
Bauer DLV
(2018)
Influenza Virus Mounts a Two-Pronged Attack on Host RNA Polymerase II Transcription.
in Cell reports
Dadonaite B
(2019)
The structure of the influenza A virus genome
in Nature Microbiology
Dadonaite B
(2017)
The structure of the influenza A virus genome
Dadonaite B
(2016)
Filamentous influenza viruses.
in The Journal of general virology
Eaton JD
(2018)
Xrn2 accelerates termination by RNA polymerase II, which is underpinned by CPSF73 activity.
in Genes & development
Fan H
(2019)
Structures of influenza A virus RNA polymerase offer insight into viral genome replication.
in Nature
Fodor E
(2013)
The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication.
in Acta virologica
Gabriel G
(2014)
Molecular determinants of pathogenicity in the polymerase complex.
in Current topics in microbiology and immunology
Hawksworth A
(2020)
Proteomics as a tool for live attenuated influenza vaccine characterisation.
in Vaccine
Hengrung N
(2015)
Crystal structure of the RNA-dependent RNA polymerase from influenza C virus.
in Nature
Ho JSY
(2020)
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.
in Cell
Hutchinson EC
(2014)
Conserved and host-specific features of influenza virion architecture.
in Nature communications
Hutchinson EC
(2013)
Transport of the influenza virus genome from nucleus to nucleus.
in Viruses
Killip MJ
(2015)
Influenza virus activation of the interferon system.
in Virus research
Killip MJ
(2017)
Single-cell studies of IFN-ß promoter activation by wild-type and NS1-defective influenza A viruses.
in The Journal of general virology
Krug R
(2013)
Textbook of Influenza
Lakdawala SS
(2016)
Moving On Out: Transport and Packaging of Influenza Viral RNA into Virions.
in Annual review of virology
Lakdawala SS
(2014)
Influenza a virus assembly intermediates fuse in the cytoplasm.
in PLoS pathogens
Long JC
(2016)
The PB2 Subunit of the Influenza A Virus RNA Polymerase Is Imported into the Mitochondrial Matrix.
in Journal of virology
Martínez-Alonso M
(2016)
RNA-Free and Ribonucleoprotein-Associated Influenza Virus Polymerases Directly Bind the Serine-5-Phosphorylated Carboxyl-Terminal Domain of Host RNA Polymerase II.
in Journal of virology
Nilsson BE
(2017)
Role of the PB2 627 Domain in Influenza A Virus Polymerase Function.
in Journal of virology
Nilsson-Payant B
(2018)
The Surface-Exposed PA 51-72 -Loop of the Influenza A Virus Polymerase Is Required for Viral Genome Replication
in Journal of Virology
Paterson D
(2014)
Host restriction of influenza virus polymerase activity by PB2 627E is diminished on short viral templates in a nucleoprotein-independent manner.
in Journal of virology
Resa-Infante P
(2015)
Targeting Importin-a7 as a Therapeutic Approach against Pandemic Influenza Viruses.
in Journal of virology
Riedl W
(2018)
Dusting for flu's fingerprints.
in Nature microbiology
Robb NC
(2019)
Real-time analysis of single influenza virus replication complexes reveals large promoter-dependent differences in initiation dynamics.
in Nucleic acids research
Robb NC
(2016)
Single-molecule FRET reveals the pre-initiation and initiation conformations of influenza virus promoter RNA.
in Nucleic acids research
Serna Martin I
(2018)
A Mechanism for the Activation of the Influenza Virus Transcriptase.
in Molecular cell
Serna Martin I
(2018)
A Mechanism for the Activation of the Influenza Virus Transcriptase.
in Molecular cell
Te Velthuis AJ
(2016)
Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis.
in Nature reviews. Microbiology
Te Velthuis AJ
(2013)
Uncoupling of influenza A virus transcription and replication through mutation of the unpaired adenosine in the viral RNA promoter.
in Journal of virology
Te Velthuis AJ
(2016)
The role of the priming loop in influenza A virus RNA synthesis.
in Nature microbiology
Te Velthuis AJW
(2018)
Mini viral RNAs act as innate immune agonists during influenza virus infection.
in Nature microbiology
Tomescu AI
(2014)
Single-molecule FRET reveals a corkscrew RNA structure for the polymerase-bound influenza virus promoter.
in Proceedings of the National Academy of Sciences of the United States of America
Turrell L
(2015)
Regulation of influenza A virus nucleoprotein oligomerization by phosphorylation.
in Journal of virology
Van Wilgenburg B
(2016)
MAIT cells are activated during human viral infections.
in Nature communications
York A
(2013)
Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus.
in Proceedings of the National Academy of Sciences of the United States of America
York A
(2013)
Biogenesis, assembly, and export of viral messenger ribonucleoproteins in the influenza A virus infected cell.
in RNA biology
Description | Invited member to join the board of directors of the European Scientific Working group on Influenza (ESWI) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
URL | http://eswi.org/home/about-eswi/members-and-associate-members/ |
Description | Conference Grant |
Amount | € 880 (EUR) |
Organisation | European Scientific Working group on Influenza (ESWI) |
Sector | Charity/Non Profit |
Country | Belgium |
Start | 08/2017 |
End | 09/2017 |
Description | Junior Research Fellowship |
Amount | £750 (GBP) |
Organisation | University of Oxford |
Department | Worcester College Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2013 |
End | 09/2014 |
Description | Lockey Grant |
Amount | £250 (GBP) |
Organisation | Lockey Committee |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2014 |
End | 10/2014 |
Description | Programme Grant |
Amount | £1,800,000 (GBP) |
Funding ID | MR/R009945/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2023 |
Description | Single-molecule analysis of influenza virus transcription and replication |
Amount | £420,000 (GBP) |
Funding ID | MR/N010744/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2016 |
End | 03/2019 |
Description | Society of General Microbiology Travel Award |
Amount | £350 (GBP) |
Organisation | Society of General Microbiology |
Sector | Charity/Non Profit |
Country | European Union (EU) |
Start | 08/2014 |
End | 10/2014 |
Title | Purification of influenza virions by haemadsorption and ultracentrifugation |
Description | A protocol for the purification of influenza virus virions published on Protocol Exchange from Nature Protocols. Protocol Exchange is an open resource where the community of scientists pool their experimental know-how to help accelerate research. |
Type Of Material | Technology assay or reagent |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Positive feedback from the research community commenting that they find the protocol very helpful. |
URL | http://www.nature.com/protocolexchange/protocols/3315 |
Title | Recombinant influenza virus RNA polymerase |
Description | We developed a Multibac system for the expression of milligram quantities of the influenza virus RNA polymerase in insect cells and procedures for its purification. |
Type Of Material | Technology assay or reagent |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | The expression and purification of large quantities of the influenza virus RNA polymerase allowed us to determine its high resolution structure using x-ray crystallography. We provided the technology to others to investigate various aspects of polymerase function as well as employing it as a tool for the development of novel antivirals tatgeting the influenza virus RNA polymerase. |
Title | SHAPE and SPLASH |
Description | We have adopted a new methods, SHAPE and SPLASH, to analyse the secondary RNA structure of the influenza virus genome and RNA-RNA interactions within the genome, in order to explain how the eight RNA genome segments of influenza A virus assemble into a budding virion. . |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | We have been contacted by several laboratories to establish collaborations or seeking advice on the transfer of these methods to allow their use for the analysis of other RNA viruses. |
URL | https://www.biorxiv.org/content/early/2017/12/21/236620 |
Title | FluPolC Structure 5D98 |
Description | Model of influenza C virus polymerase structure |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | A new model for the influenza virus polymerase explaining its activation upon promoter binding. |
URL | http://www.rcsb.org/pdb/explore.do?structureId=5D98 |
Title | FluPolC structure 5D9A |
Description | Model for the influenza C virus polymerase complex. |
Type Of Material | Computer model/algorithm |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | A new model for the activation of the influenza virus RNA polymerase complex. |
URL | http://www.rcsb.org/pdb/explore/explore.do?structureId=5D9A |
Title | Influenza B virus polymerase 6F5O |
Description | Coordinates of FluPolB fitted into the cryo-EM map of promoter vRNA bound FluPolC |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | None yet. |
URL | http://www.rcsb.org/structure/6F5O |
Title | Influenza C virus polymerase bound to Pol II CTD 6F5P |
Description | Coordinates of pS5-CTD bound FluPolC |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | None yet. |
URL | http://www.rcsb.org/structure/6F5P |
Title | Interactome of the influenza A virus transcription/replication machinery |
Description | We have analysed the cellular interactome of the influenza virus RNA polymerase and raw files for all mass spectra used in the analysis have been deposited at the Mass spectrometry Interactive Virtual Environment (MassIVE; Center for Computational Mass Spectrometry at the University of California, San Diego) and can be accessed at http://massive.ucsd.edu/ProteoSAFe/datasets.jsp using the MassIVE ID MSV000078741. |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | The data are freely available to other researchers and can be used to address the role of specific host factors in influenza virus replication. |
URL | http://massive.ucsd.edu/ProteoSAFe/static/massive.jsp?redirect=auth |
Title | Sequencing data Pol II mNETSeq NCBI SRA: SRP132032 |
Description | Effect of influenza virus infection on host RNA polymerase II transcription - mNETSeq data of Pol II |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | None yet. |
URL | https://www.ncbi.nlm.nih.gov/sra/?term=SRP132032 |
Title | Sequencing data of influenza virus infected cells - mvRNAs SRP158565 |
Description | Sequencing data of influenza virus infected cells - mvRNAs |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | None yet. |
URL | https://www.ncbi.nlm.nih.gov/sra?term=SRP158565 |
Description | EM structural studies |
Organisation | University of Oxford |
Department | Wellcome Trust Centre for Human Genetics |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | We provided material for structural studies using electron microscopy. |
Collaborator Contribution | The partner provided expertise, data analysis and access to equipment to perform structural analysis by electron microscopy. |
Impact | 24155385 |
Start Year | 2012 |
Description | Janssen polymerase Inhibitors |
Organisation | Janssen Pharmaceutica NV |
Country | Belgium |
Sector | Private |
PI Contribution | The aim of this collaboration is to analyse binding of lead compounds with potential antiviral activity against influenza virus that bind the influenza virus RNA polymerase. We prepared recombinant influenza virus polymerase and used x-ray crystallography to obtain structural information on the binding of a selection of compounds provided by Janssen. |
Collaborator Contribution | Janssen provided compounds for analysis. |
Impact | PMID: 31647875 |
Start Year | 2018 |
Description | Medimmune RNA project |
Organisation | AstraZeneca |
Department | MedImmune |
Country | United Kingdom |
Sector | Private |
PI Contribution | The cold-adapted live attenuated influenza virus vaccine, used in the UK childhood influenza immunisation programme, is a reassortant virus containing 6 RNA gene segments from a donor virus ensuring high growth in embryonated chicken eggs and 2 RNA gene segments from seasonal influenza to ensure the expression of the new antigens. Our team proposed that the vaccine could be improved by ensuring full compatibility between the RNA segments. Towards this aim, we used SPLASH to identify RNA-RNA interactions in the donor virus as well as reassortant vaccine viruses (as described in our publication Dadonaite et al Nature Microbiol 2019). This work could allow Medimmune to optimise the RNA sequence of vaccine viruses, potentially improving vaccine efficacy. We provided expertise and carried out SPLASH on samples provided by Medimmune, analysed and interpreted the data. |
Collaborator Contribution | Medimmune provided RNA samples from vaccine viruses for analysis by SPLASH. |
Impact | The work has identified RNA-RNA interactions in influenza vaccine viruses. This is helpful in designing improved versions of the cold-adapted live attenuated influenza virus vaccine. |
Start Year | 2019 |
Description | Single molecule studies |
Organisation | University of Oxford |
Department | Department of Physics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided materials for investigating influenza virus RNA polymerase - promoter interactions at the single molecule level. |
Collaborator Contribution | The partner contributed technology to analyse protein-RNA complexes at the single molecule level. |
Impact | PMID: 25071209; PMID: 27694620; PMID: 27572643 |
Start Year | 2010 |
Description | University of St Andrews |
Organisation | University of St Andrews |
Department | Centre for Biomolecular Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided expertise in influenza virus molecular biology, especially in techniques to analyse levels of viral RNAs in complex samples. |
Collaborator Contribution | The partner brought expertise in innate immunology, especially in techniques used to analyse the activation of the interferon pathway. |
Impact | PMID: 27983470; PMID: 25678267; a further joint publication is in preparation |
Start Year | 2014 |
Description | Abingdon School Biology Society |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk sparked questions and stimulated discussion. Positive feedback from the society. |
Year(s) Of Engagement Activity | 2014 |
Description | Amgen Biotech Experience programme |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Talking to school teachers about science background and current work. The idea of the programme is to introduce schoolchildren to molecular biology techniques by lending lab-grade equipment to schools; a teacher training day, to provide a view on how these techniques are actually used in research. |
Year(s) Of Engagement Activity | 2015 |
Description | BBC Radio 4 interview for BBC Inside Science |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Our study published in Nature Microbiology (te Velthuis AJW, Long JC, Bauer DLV, Fan RLY, Yen HL, Sharps J, Siegers JY, Killip MJ, French H, Oliva-Martín MJ, Randall RE, de Wit E, van Riel D, Poon LLM, Fodor E.Mini viral RNAs act as innate immune agonists during influenza virus infection. Nat Microbiol. 2018 Nov;3(11):1234-1242. doi: 10.1038/s41564-018-0240-5. Epub 2018 Sep 17) has attracted a wide media interest, including an interview request from BBC Radio 4 for the BBC Inside Science programme. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.bbc.co.uk/programmes/b0bkpjp5 |
Description | Creativity Foundation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Creativity Foundation legacy award - talked about creativity & the scientific process with ~30 young students in multiple disciplines (arts, business, science, etc) over the course of 3-day weekend event. Talk sparked questions and discussion afterwards. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.creativity-found.org/about/ |
Description | Diamond Newsletter - Giving structural insight into influenza virus |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | A publication through the Diamond Light Source News website highlighted our work on the influenza virus polymerase structure. The publication includes an animation depicting the transcription and replication mechanisms of influenza virus; this animation has become a useful tool in presenting our work to wider audiences as well as a teaching tool within university setting. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.diamond.ac.uk/Home/News/LatestNews/2022/04-11-22.html |
Description | Garsington Primary School |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk sparked questions and discussion. Positive feedback from school. |
Year(s) Of Engagement Activity | 2014 |
Description | Linacre Alumni Weekend |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Linacre College informal Seminar and Reception open to all Linacre Members and their guests in conjunction with Oxford University's Meeting Minds Alumni Weekend in Oxford. The occasion provided an opportunity to present our research to Linacre Members, current and past, and their guests. The presentation sparked questions and discussion afterwards, during an informal reception. |
Year(s) Of Engagement Activity | 2016 |
Description | Mapping the structure of the influenza A virus genome |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Our work, published in Nature Microbiology (Dadonaite et al Nat Micro 2019), mepping the structure of the influenza A virus genome has been reported in the MedicalXpress. |
Year(s) Of Engagement Activity | 2019 |
URL | https://medicalxpress.com/news/2019-07-influenza-virus-genome.html |
Description | Marlborough CofE secondary school |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk on influenza and pandemic emergence sparked questions and discussion afterwards. Positive feedback from school. |
Year(s) Of Engagement Activity | 2014 |
Description | Media interest in influenza virus polymerase structure |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Nature Studies Investigate Influenza Polymerase Genomeweb New structure for human flu virus protein Phys.org ?? ? ???? ????? A? ????? RNA ??? RNA ?? ?? ?? ??(Nature) Nature Asia First comprehensive structural data on a key flu protein-it's central to infection MedicalXpress ?? ? ???? ????? A? ????? RNA ??? RNA ?? ?? ?? ?? Nature Asia |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.nature.com/articles/s41586-019-1530-7/metrics |
Description | Oxfordshire Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | An estimated 120 people (c. one group of c. 3 children and 2 adults every 10 min for 4 hours) participated in an interactive demonstration on where new influenza viruses come from was carried out as part of the OSF launch event in Bonn Sq, central Oxford (from 12:30-4:30pm). A game involving chocolates was used to describe (i) infection (for younger participants) and (ii) the generation of 'hybrid' influenza viruses during mixed infection (for older participants). Posters, etc, showing the virus were also displayed and discussed. Expression of interest about basic biological sciences by the public; the equipment for the stall has also been loaned out to demonstrators to help discuss influenza at an Oxford Brookes University Science Festival in September 2013. |
Year(s) Of Engagement Activity | 2013 |
Description | Press release - Influenza virus molecules set immune response into overdrive |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Our study published in Nature Microbiology (te Velthuis AJW, Long JC, Bauer DLV, Fan RLY, Yen HL, Sharps J, Siegers JY, Killip MJ, French H, Oliva-Martín MJ, Randall RE, de Wit E, van Riel D, Poon LLM, Fodor E.Mini viral RNAs act as innate immune agonists during influenza virus infection. Nat Microbiol. 2018 Nov;3(11):1234-1242. doi: 10.1038/s41564-018-0240-5. Epub 2018 Sep 17) has attracted a wide media interest. A press release was made through the News Offices of the University of Oxford and Cambridge and the news was picked up by several media outlets, including BBC Radio 4, MedicalXpress, MedPage Today, Times of Malta, Health Canal, Technology Networks. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.ox.ac.uk/news/2018-09-20-influenza-virus-molecules-set-immune-response-overdrive |
Description | Press release - New structure for human flu virus protein |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | A press release through the Diamond Light Source website highlighted our work on the influenza virus polymerase structure. This work, published in Nature (Fan et al Nature 2019), reported the first high-resolution structures of polymerases from medically relevant human and avian influenza A viruses and proposed a mechanism for how the RNA polymerase of influenza virus replicates the viral RNA genome. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.diamond.ac.uk/Science/Research/Highlights/2019/new-structure-human-flu-virus.html |
Description | Press release on publication of the influenza virus RNA polymerase structure in Nature |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release related to a publication on the high resolution structure of an influenza virus RNA polymerase complex, published in Nature (Hengrung N, El Omari K, Serna Martin I, Vreede FT, Cusack S, Rambo RP, Vonrhein C, Bricogne G, Stuart DI, Grimes JM, Fodor E. Crystal structure of the RNA-dependent RNA polymerase from influenza C virus. Nature. 2015 Nov 5;527(7576):114-7. doi: 10.1038/nature15525). The press release was made through the University of Oxford and Diamond Press Offices, with commentary from the MRC. http://www.diamond.ac.uk/Home/News/LatestNews/27-10-15.html |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.diamond.ac.uk/Home/News/LatestNews/27-10-15.html |
Description | The Conversation - Why pandemic influenza is so deadly - revealed |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Our study published in Nature Microbiology (te Velthuis AJW, Long JC, Bauer DLV, Fan RLY, Yen HL, Sharps J, Siegers JY, Killip MJ, French H, Oliva-Martín MJ, Randall RE, de Wit E, van Riel D, Poon LLM, Fodor E.Mini viral RNAs act as innate immune agonists during influenza virus infection. Nat Microbiol. 2018 Nov;3(11):1234-1242. doi: 10.1038/s41564-018-0240-5. Epub 2018 Sep 17) has been covered in The Conversation. |
Year(s) Of Engagement Activity | 2018 |
URL | https://theconversation.com/why-pandemic-influenza-is-so-deadly-revealed-103115 |
Description | The Scientist |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Our paper published in Nature Communications (Hutchinson et al 2014) sparked interest from the magazine The Scientist. We have given an interview and the magazine published an article highlighting our research on the "Anatomy of Influenza Virus"; see http://www.the-scientist.com/?articles.view/articleNo/41013/title/Anatomy-of-a-Virus/. The wider public becoming aware of our results of research. |
Year(s) Of Engagement Activity | 2014 |