Dissecting the molecular pathways of MDV oncoprotein Meq for understanding pathogenesis and aid vaccine development
Lead Research Organisation:
The Pirbright Institute
Department Name: Avian Oncogenic Viruses
Abstract
Infectious diseases result in direct and indirect losses at various steps of poultry farming and amongst them neoplastic disease caused by viruses is a major economic problem faced by the poultry industry worldwide. The oncogenic viruses causing neoplastic infection in chickens are herpesviruses comprising of Marek's disease virus (MDV) and retroviruses comprising of reticuloendotheliosis virus (REV) and avian leucosis virus (ALV). Marek's disease (MD) is a common disease of chickens involving paralysis and commonly death from the growth of highly malignant T lymphomas (cancers of white blood cells). MD is caused by a transmissible agent MDV. MDV is very contagious and is a major threat to the poultry industry worldwide. The estimated total loss from this disease worldwide is up to $2 billion. Presently, it is controlled by vaccination, and nearly 22 billion vaccine doses a year are used in an attempt to control the disease. Despite widespread vaccination, the threat from this disease is on increase due to continued evolution of MDV towards greater virulence, and more fundamental studies to understand the mechanisms by which this virus causes cancer is needed to develop more effective control programmes. Meq is the major oncoprotein in MDV induced tumorigenesis. Previously, we have identified Meq targetome in cancer cells. In this new grant proposal, to be carried out jointly between the Pirbright Institute and Roslin Institute, we want to extend these studies to obtain detailed information on the role of Meq and its targets in MDV induced oncogenesis using a number of advanced approaches including CRISPR/Cas9 genome editing we have recently established in the lab and rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) for Meq interactome identification. The study is very important to understand the mechanisms by which this virus induces cancer, some of which are valuable in understanding cancer in other species including humans. Finally, the findings from the project will be very valuable in developing new approaches for the control of cancers caused by oncogenic viruses.
Technical Summary
The objectives of this project are to dissect the molecular pathways of MDV oncoprotein Meq for understanding pathogenesis and aid vaccine development. Meq is the major oncoprotein in MDV induced tumorigenesis. Yet the underlying molecular mechanisms are not fully understood. Our overall aim is to dissect the molecular events during Meq-induced neoplastic transformation exploiting the recent technological advances such as the CRISPR/Cas9 genome editing and rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME). Specifically, we will investigate the role of Meq and its cancer related targets in maintaining the transformed phenotype of MDV1 cell line by deleting/mutating Meq/Meq-targets using CRISPR/Cas9 genome editing tool in MDV transformed cell line and perform proliferation assay for cell growth and RNA-seq for gene expression and pathways involved. RIME will be carried out to identify Meq interactome. Finally, we will delete Meq from very virulent plus (vv+) MDV1 virus and also to replace vv+ Meq with vaccine strain CVI988 Meq using CRISPR/Cas9 system and ask the question "Are the mutant viruses could be used as vaccine?" The data obtained will allow us to understand the role of Meq in maintaining the transformed phenotype and molecular interactions and pathways involved during MDV-induced oncogenesis.
Planned Impact
Poultry industry is a rapidly growing sector crucial for the global food security, acting as a major source of protein for the growing world population. Marek's disease (MD) is one of the major disease of poultry which causes serious economic losses and the global estimate of losses from MD is approximately $2 billion annually. Detailed understanding of the molecular basis of MDV induced oncogenesis, as the current proposal aims to achieve, will benefit development of new strategies for control.The beneficiaries of this research will include academic scientists, the poultry breeding companies and vaccine production companies, the Pirbright Institute, the BBSRC and its stakeholders such as Defra and the UK farming industry.
The research will have general impact with the wider scientific community, veterinary and medical practitioners, students and general public. Engagement with these diverse groups will be achieved via meetings, articles in the trade press, tailored web pages, press releases to the media and outreach events in schools.
In the longer term the research may lead to medical benefits by improving control of human virus pathogens which will benefit the UK MRC and UK department of Health, the pharmaceutical industry and international organization such as the World Health Organization.
If the proposed studies lead to new approaches for controlling MDV or other viral diseases, additional funding will be sought from relevant funding agencies and other sources for further development. There is extensive experience within the Pirbright Institute of patent applications and commercialisations, new opportunities will feed into an established system for technology development and knowledge transfer by the Pirbright Business Development group.
The research will have general impact with the wider scientific community, veterinary and medical practitioners, students and general public. Engagement with these diverse groups will be achieved via meetings, articles in the trade press, tailored web pages, press releases to the media and outreach events in schools.
In the longer term the research may lead to medical benefits by improving control of human virus pathogens which will benefit the UK MRC and UK department of Health, the pharmaceutical industry and international organization such as the World Health Organization.
If the proposed studies lead to new approaches for controlling MDV or other viral diseases, additional funding will be sought from relevant funding agencies and other sources for further development. There is extensive experience within the Pirbright Institute of patent applications and commercialisations, new opportunities will feed into an established system for technology development and knowledge transfer by the Pirbright Business Development group.
Organisations
- The Pirbright Institute (Lead Research Organisation)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Henan Academy of Agricultural Sciences (Collaboration)
- Henan Agricultural University (Collaboration)
- University of Surrey (Collaboration)
- Moy Park (Collaboration)
- South China Agricultural University (Collaboration)
- DIAMOND LIGHT SOURCE (Collaboration)
People |
ORCID iD |
YONGXIU YAO (Principal Investigator) | |
Venugopal Nair (Co-Investigator) |
Publications
Zhang Y
(2018)
Application of CRISPR/Cas9 Gene Editing System on MDV-1 Genome for the Study of Gene Function.
in Viruses
Yao Y
(2019)
Herpesvirus of Turkeys (Meleagridis Herpesvirus 1) Encodes a Functional MicroRNA-221 Homolog with High Sequence Conservation
in Advances in Microbiology
Tang N
(2019)
Generating Recombinant Avian Herpesvirus Vectors with CRISPR/Cas9 Gene Editing.
in Journal of visualized experiments : JoVE
Li T
(2019)
Co-infection of vvMDV with multiple subgroups of avian leukosis viruses in indigenous chicken flocks in China.
in BMC veterinary research
Yang F
(2020)
Antiviral effect of baicalin on Marek's disease virus in CEF cells.
in BMC veterinary research
Description | One of the key findings of this project was the establishment of an efficient pipeline for in situ CRISPR editing of the Marek's disease virus (MDV) genome in lymphoma-derived cell lines. Using this approach, we have demonstrated viral genes such as pp38 and MDV-miR-M4 are not essential for maintaining the transformed phenotype. On the other hand, deletion of MDV-encoded oncogene Meq or mutations preventing its interactions resulted in cell death demonstrating the essential role of Meq in transformation. In addition, we have demonstrated that targeted deletion of the MDV-2 essential gene glycoprotein B (gB) from MSB-1 cells coinfected with oncogenic MDV-1 and non-pathogenic MDV-2 viruses induces total inhibition of MDV-2 virus replication on co-cultivated CEF, with no effect on MDV-1 replication. The identified viral genes critical for reactivation/inhibition of viruses will be useful as targets for development of de novo disease resistance in chickens to avian pathogens. Another key finding was the establishment of CRISPRa (CRISPR activation) system to activate the latent viral genes in MDV cell lines. Using this approach, we have demonstrated targeted activation of pp38/pp24 expression in LCLs triggers lytic replication of MDV in MDV-transformed cell lines. Following the successful targeted editing of the MDV-transformed cell lines, we used CRISPR/Cas9 gRNA library screening approach to identify the host factors required for the maintenance of the transformed phenotype of MDV-transformed cells. 339 host genes have been identified being essential for maintaining the transformed phenotype of MDV cell line. Gene pathway analysis showed a significant mitochondrial signature. Further analysis using several known mitochondrial inhibitors suggests that mitochondrial function is critical for the continued proliferation of HP8 cells. The methylation calling from the recent Pacbio sequencing of different MDV cell lines demonstrated the difference at certain loci between different cell lines. |
Exploitation Route | Establishment of the pipeline for in situ CRISPR editing of lymphoma-derived cell lines, gives the opportunity for the identification of critical viral and host genes involved in features such as virus-host interactions, neoplastic transformation, and virus latency. The identified genes could serve as targets for inducing de novo genetic resistance using gene editing approaches. Determination of the global myc-binding profiles in transformed macrophages could provide insights into its role in transformation. Achieving rapid detection of ALV infection is imperative in effective control of the spread of ALVs. The methylation data could be integrated with the transcriptomes data from the same cells to determine the oncogenic pathways and develop models/predictions of oncogenesis. |
Sectors | Agriculture Food and Drink |
URL | https://www.mdpi.com/1999-4915/11/5/391 |
Description | BBSRC IAA The Pirbright Institute |
Amount | £300,000 (GBP) |
Funding ID | BB/S506680/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2021 |
Description | CRISPR/Cas system-based molecular diagnostics for avian viral pathogens |
Amount | £21,263 (GBP) |
Organisation | The Pirbright Institute |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2020 |
End | 03/2020 |
Description | Collaborative partnership for establish of PhysioMimix™ OOC system, part of Pirbright Institute Flexible Talent Mobility Account |
Amount | £180,000 (GBP) |
Funding ID | BB/S507945/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2020 |
End | 12/2020 |
Description | Development of CVI-988 based recombinant vaccine |
Amount | £240,000 (GBP) |
Organisation | Eco Animal Health Ltd |
Sector | Private |
Country | United Kingdom |
Start | 07/2019 |
End | 03/2021 |
Description | Development of CVI988 based recombinant vaccine |
Amount | £238,000 (GBP) |
Organisation | Eco Animal Health Ltd |
Sector | Private |
Country | United Kingdom |
Start | 03/2023 |
End | 02/2024 |
Description | Development of HVT vectored vaccine |
Amount | £100,000 (GBP) |
Organisation | MSD Animal Health |
Sector | Private |
Country | United Kingdom |
Start | 11/2022 |
End | 04/2023 |
Description | Development of HVT-ND using CRISPR/Cas9 system |
Amount | £188,317 (GBP) |
Organisation | HIPRA |
Sector | Private |
Country | Spain |
Start | 05/2022 |
End | 05/2023 |
Description | Development of avian herpesvirus vector vaccines for poultry |
Amount | £772,000 (GBP) |
Organisation | MSD Animal Health |
Sector | Private |
Country | United Kingdom |
Start | 01/2024 |
End | 12/2026 |
Description | Development of avian herpesvirus vector vaccines for poultry |
Amount | £432,000 (GBP) |
Organisation | MSD Animal Health |
Sector | Private |
Country | United Kingdom |
Start | 01/2021 |
End | 12/2023 |
Description | Development of improved HVT based vaccines using CRISPR/Cas9 system |
Amount | £258,820 (GBP) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2021 |
End | 12/2022 |
Description | Development of multivalent HVT vectored vaccines |
Amount | £15,169 (GBP) |
Organisation | Vaxxinova |
Sector | Private |
Country | Netherlands |
Start | 05/2022 |
End | 05/2023 |
Description | Effects of co-infections on Marek's disease in poultry and development of novel recombinant Marek's disease virus vector vaccines |
Amount | £562,000 (GBP) |
Funding ID | BB/X017575/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2023 |
End | 09/2026 |
Description | PhD studentship |
Amount | £130,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2022 |
End | 09/2026 |
Description | PhD studentship |
Amount | £91,830 (GBP) |
Organisation | The Pirbright Institute |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2019 |
End | 03/2023 |
Description | PhD studentship |
Amount | £110,000 (GBP) |
Organisation | The Pirbright Institute |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2022 |
End | 03/2026 |
Description | Production of HVT vectored VhH construct |
Amount | £155,000 (GBP) |
Organisation | Eco Animal Health Ltd |
Sector | Private |
Country | United Kingdom |
Start | 01/2020 |
End | 06/2020 |
Description | Seeding Catalyst Award |
Amount | £29,683 (GBP) |
Funding ID | ISCF-TFPSA-Pirbright |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2018 |
End | 02/2019 |
Title | Establishment of an efficient CRISPR/Cas9 gRNA library screening to identify the host factors required for maintaining the transformed phenotype of MDV tumour cell lines |
Description | Herpesviruses are large dsDNA viruses that cause widespread, lifelong latent infections in different hosts, through multiple virus-host interactions to create a delicate balance between the virus and the host. CRISPR/Cas9-based gene editing is emerging as a powerful tool to investigate the precise determinants of latency in a number of herpesvirus infections. Marek's disease virus (MDV-1) is a lymphotropic a-herpesvirus associated with latent infections and malignant CD4+ T-cell lymphomas in chicken. MDV-1 has a two-phase life cycle, consisting of a lytic and a latent phase, the latter closely associated with the oncogenesis of the virus, yet the underlying molecular mechanisms of cell transformation remain unclear. Better understanding of the factors that maintain the latency of the virus will provide insights into novel intervention strategies to interfere with the neoplastic process. We have used a high throughput genome-wide CRISPR/Cas9 gene knockout strategy, combined with next generation sequencing to identify the genes critical for maintenance of the transformed phenotype. 339 host genes have been identified being essential for maintaining the transformed phenotype of MDV cell line. |
Type Of Material | Technology assay or reagent |
Year Produced | 2023 |
Provided To Others? | No |
Impact | Establishment of the pipeline of CRISPR library screening in chicken cell lines has given the opportunity for the identification factors associated with disease pathogenesis and neoplastic transformation. The identified genes could serve as targets for inducing de novo genetic resistance using gene editing approaches. |
Title | Establishment of an efficient CRISPR/Cas9-based screening pipeline for herpesviruses to study the gene function and streamline the vector platform for recombinant vaccine development |
Description | The development of both cosmid DNA and Bacterial artificial chromosome (BAC) technologies has greatly facilitated the introduction of mutations into the viral genomes of herpesviruses to study gene functions. However, cloning of viral genomes as BAC plasmid and subsequent mutagenesis is inefficient, time-consuming and may introduce mutations by repeated passages. Following our success in efficient CRISPR/Cas9 editing of the MDV genome in both replicating virus and MDV transformed cell lines and of HVT genome for the recombinant vaccine development, we have developed an efficient CRISPR/Cas9-based screening pipeline for herpesviruses to identify the essential/non-essential genes for study of the gene function and streamline the vector platform for recombinant vaccine development. |
Type Of Material | Technology assay or reagent |
Year Produced | 2022 |
Provided To Others? | No |
Impact | Identification of essential and non-essential genes of herpesviruses provided opportunities to study gene function in vitro and in vivo. Knocking out the non-essential genes in the HVT vector can enhance HVT replication in vivo enabling recombinant HVT-based vaccines to induce stronger immune responses. |
Title | The establishment of an efficient pipeline for in situ CRISPR editing of the Marek's disease virus (MDV) genome in lymphoma-derived cell lines |
Description | The lymphoblastoid cell lines (LCLs) derived from MD lymphomas have served as valuable resources to study virus-host molecular interactions in transformed cells. However, detailed investigations into the functional role of different viral and host determinants in these cells have been difficult due to the lack of tools for in situ manipulation of viral/host genomes in MDV-transformed cell lines. Our recent success in efficient CRISPR/Cas9 editing of the MDV genome in LCLs has demonstrated the potential for targeted editing to dissect the regulatory pathways involved in latency, transformation, reactivation and lytic switch. |
Type Of Material | Technology assay or reagent |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Using this approach, we have demonstrated viral genes such as pp38 and MDV-miR-M4 are not essential for maintaining the transformed phenotype. On the other hand, deletion of MDV-encoded oncogene Meq or mutations preventing its interactions resulted in cell death demonstrating the essential role of Meq in transformation. |
URL | https://www.mdpi.com/1999-4915/10/6/279 |
Description | Dr. Manman Dai |
Organisation | South China Agricultural University |
Country | China |
Sector | Academic/University |
PI Contribution | Provided knowledge and expertise on avian disease research |
Collaborator Contribution | Provided knowledge and expertise on avian disease research |
Impact | Two joint publications have been generated: 1. Dai M, Zhu S, An Z, You B, Li Z, Yao Y, Nair V, Liao M. Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis. PLoS Pathog. 2023 Oct 11;19(10):e1011685. doi: 10.1371/journal.ppat.1011685. eCollection 2023 Oct. 2. Dai M, Sun H, Zhao L, Wu Q, You B, Xu F, Liao J, Zhu S, Li Z, Yao Y, Nair V, Liao M. Duck CD8 + T Cell Response to H5N1 Highly Pathogenic Avian Influenza Virus Infection In Vivo and In Vitro. J Immunol. 2022 Aug 8;ji2101147. doi: 10.4049/jimmunol.2101147. |
Start Year | 2022 |
Description | Effects of co-infections on Marek's disease in poultry, and development of novel recombinant Marek's disease virus vector vaccines |
Organisation | Moy Park |
Country | United Kingdom |
Sector | Private |
PI Contribution | This is a joint BBSRC funded project on investigation "Effects of co-infections on Marek's disease in poultry, and development of novel recombinant Marek's disease virus vector vaccines" between Pirbright, Moy Park and Slate Hall Veterinary Practice. Pirbright team works on the detailed investigation of prevalence of naturally occurring MDV-2 (Marek's disease virus serotype 2) infection in the field in UK; isolation and characterisation of MDV-2 field strains and development of novel MDV-2-based recombinant vaccine MDV2-IBD-ND which will protect chickens against Marek's disease, infectious bursal disease and Newcastle disease. |
Collaborator Contribution | Moy Park will collect the field samples and investigate the effect of MDV-2 on flock productivity and disease. |
Impact | Too early |
Start Year | 2023 |
Description | Finn Frey |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Worked together to identify the host factors involved in MDV latency |
Collaborator Contribution | Provided chicken gRNA library for screening of MDV cell line |
Impact | Not yet |
Start Year | 2018 |
Description | Joint PhD project on "Exploring ultrastructural features of the virus-host interactions of MDV" |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | Pirbright team provided expertise on MDV biology part of the project. |
Collaborator Contribution | Diamond team provided expertise on using the state-of-the-art tools to gain structural biology insights into the distinct features of MDV-host cell interactions. |
Impact | No outputs yet. |
Start Year | 2022 |
Description | Joint PhD project on "Using Marek's Disease Virus to understand the RNA world of alphaherpesviruses" |
Organisation | University of Surrey |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Surrey team has provided expertise on characterization of Marek's disease virus encoded vhs protein function in vitro. |
Collaborator Contribution | Pirbright team has provided expertise in making the mutant virus of vhs deleted MDV and study the role of vhs in the context of infection in vitro and in vivo. |
Impact | The student Sophie Cutts has abstract accepted for oral presentation in both Microbiology Society Annual Conference 2024 to be held in Edinburgh 8-11 April and 14th International Symposium on Marek's Disease and Avian Herpesvirus to be held at St. Louis, USA from 12th-14th July, 2024. |
Start Year | 2022 |
Description | Mick Watson |
Organisation | University of Edinburgh |
Department | The Roslin Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provide samples for host-virus interaction study of MDV |
Collaborator Contribution | Data analysis of RNA-seq on CRISPR/Cas9 edited MDV cell lines. |
Impact | One publication from this collaboration: Zhang Y, Tang N, Luo J, Teng M, Moffat K, Shen Z, Watson M, Nair V#, Yao Y#. Marek's disease virus-encoded miR-155 ortholog critical for the induction of lymphomas is not essential for the proliferation of transformed cell lines. J Virol. 2019 Jun 12. pii: JVI.00713-19. doi: 10.1128/JVI.00713-19. |
Start Year | 2018 |
Description | Professor Guozhong Zhuang |
Organisation | Henan Agricultural University |
Country | China |
Sector | Academic/University |
PI Contribution | Provided knowledge and expertise on MDV research |
Collaborator Contribution | Provided samples for MDV research |
Impact | The following joint publications have been generated: 1. Sun A, Yang S, Luo J,Teng M, Xu Y, Wang R, Zhu X, Zheng L, Wu Y, Yao Y, Nair V, Zhang G, Zhuang G. UL28 and UL33 homologs of Marek's disease virus terminase complex involved in the regulation of cleavage and packaging of viral DNA are indispensable for replication in cultured cells. Veterinary Research. 2021, 52:20. 10.1186/s13567-021-00901-5 2. Sun A, Zhao X, Zhu X, Kong Z, Liao Y, Teng M, Yao Y, Luo J, Nair V, Zhuang G, Zhang G. Fully Attenuated meq and pp38 Double Gene Deletion Mutant Virus Confers Superior Immunological Protection against Highly Virulent Marek's Disease Virus Infection. Microbiol Spectr. 2022 Nov 9; doi: 10.1128/spectrum.02871-22 3. Zhuang G, Zhao X, Jin J, Zhu X, Wang R, Zhai Y, Lu W, Liao Y, Teng M, Yao Y, Nair V, Yao W, Sun A, Luo J, Zhang G. Infection phase-dependent dynamics of the viral and host N6-methyladenosine epitranscriptome in the lifecycle of an oncogenic virus in vivo. J Med Virol. 2022 Nov 18. doi: 10.1002/jmv.28324. |
Start Year | 2019 |
Description | Professor Luo |
Organisation | Henan Academy of Agricultural Sciences |
Country | China |
Sector | Academic/University |
PI Contribution | Provided knowledge, reagent and information on MDV research |
Collaborator Contribution | Provided samples and reagent for MDV research |
Impact | 11 joint publications have been generated: 1. Liu JL, Teng M, Zheng LP, Zhu FX, Ma SH, Li LY, Zhang ZH, Chai SJ, Yao Y and Luo J. Emerging Hypervirulent Marek's Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines. Viruses 2023, 15(7), 1434; doi: 10.3390/v15071434 2. Teng M, Zhu Z, Yao Y, Nair V, Zhang G, Luo J. (2023) Critical Roles of Non-coding RNAs in Avian Oncogenic Marek's Disease Herpesvirus Biology. SCIENCE CHINA Life Sciences 66 2, 251-268; https://doi.org/10.1007/s11427-022-2258-4.Teng M, Liu J, Luo Q, Zheng L, Yao Y, Nair V, Zhang G, Luo J. Efficient Screening and Characterization of Monoclonal Antibodies against MDV-1 Specific Oncoprotein Meq Using the CRISPR/Cas9 Gene Edited Viruses. Viruses, 2023, 15(4), 817; https://doi.org/10.3390/v15040817 3. Zheng L, Teng M, Li G, Zhang W, Wang W, Liu J, Li L, Yao Y, Nair V and Luo J. Current Epidemiology and Co-Infections of Avian Immunosuppressive and Neoplastic Diseases in Chicken Flocks in Central China. Viruses 2022, 14(12), 2599; https://doi.org/10.3390/v14122599 4. Teng M, Zhou Z, Yao Y, Nair V, Zhang G, Luo J. A New Strategy for Efficient Screening and Identification of Monoclonal Antibodies against Oncogenic Avian Herpesvirus Utilizing CRISPR/Cas9-Based Gene-Editing Technology. Viruses. 2022, 14(9), 2045; https://doi.org/10.3390/v14092045 5. Teng M, Yao Y, Nair V, Luo J. Latest Advances of Virology Research Using CRISPR/Cas9-Based Gene-Editing Technology and Its Application to Vaccine Development. Viruses. 2021, 13(5), 779; https://doi.org/10.3390/v13050779 6. Sun A, Yang S, Luo J,Teng M, Xu Y, Wang R, Zhu X, Zheng L, Wu Y, Yao Y, Nair V, Zhang G, Zhuang G. UL28 and UL33 homologs of Marek's disease virus terminase complex involved in the regulation of cleavage and packaging of viral DNA are indispensable for replication in cultured cells. Veterinary Research. 2021, 52:20. 10.1186/s13567-021-00901-5 7. Zhu Z, Teng M, Li H, Zheng L, Liu J, Yao Y, Nair V, Zhang G, Luo J. Virus-encoded miR-155 ortholog in Marek's disease virus promotes cell proliferation via suppressing apoptosis by targeting tumor suppressor WWOX. Veterinary Microbiology. 7 November 2020, https://doi.org/10.1016/j.vetmic.2020.108919 8. Zhu Z, Teng M, Li H, Zheng L, Liu J, Chai S, Yao Y, Nair V, Zhang G, Luo J. Marek's disease virus (Gallid alphaherpesvirus 2, GaHV-2)-encoded miR-M2-5p simultaneously promotes cell proliferation and suppresses apoptosis through RBM24 and MYOD1-mediated signaling pathways. Frontiers in Microbiology. 03 November 2020 | https://doi.org/10.3389/fmicb.2020.596422 9. Luo J, Teng M, Zai X, Tang N, Zhang Y, Mandviwala A, Reddy VRAP, Baigent S, Yao Y, Nair V. Efficient Mutagenesis of Marek's Disease Virus-Encoded microRNAs Using a CRISPR/Cas9-Based Gene Editing System. Viruses. 2020 Apr 20;12(4): E466. doi: 10.3390/v12040466. 10. Zhang Y, Tang N, Luo J, Teng M, Moffat K, Shen Z, Watson M, Nair V#, Yao Y#. Marek's disease virus-encoded miR-155 ortholog critical for the induction of lymphomas is not essential for the proliferation of transformed cell lines. J Virol. 2019 Jun 12. pii: JVI.00713-19. doi: 10.1128/JVI.00713-19. 11. Zhang Y, Luo J, Tang N, Teng M, Reddy VRAP, Moffat K, Shen Z, Nair V#, Yao Y#. Targeted Editing of the pp38 Gene in Marek's Disease Virus-Transformed Cell Lines Using CRISPR/Cas9 System. Viruses. 2019 Apr 26;11(5). pii: E391. doi: 10.3390/v11050391. |
Start Year | 2018 |
Description | Understanding the genetic resistant to Marek's disease |
Organisation | University of Surrey |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have provided the sequencing data of resistant and susceptible inbred chicken lines and crosses to be analyzed using AI for understanding the genetic resistant to Marek's disease. |
Collaborator Contribution | The collaborators contribution is to use AI for analysis to explore the determinants associated with the distinct resistance phenotype. |
Impact | No output yet. |
Start Year | 2023 |
Description | AN INTERVIEW WITH PROFESSOR VENUGOPAL NAIR |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Professor Venugopal Nair is a Research Group Leader at The Pirbright Institute, a visiting Professor of Avian Virology at the Department of Zoology, and a Jenner Investigator at the Jenner Institute, University of Oxford. He is also a member of the Microbiology Society, and in this interview, he tells us more about his research into viral diseases of livestock. |
Year(s) Of Engagement Activity | 2020 |
URL | https://microbiologysociety.org/membership/meet-our-members/focus-area-viruses/an-interview-with-pro... |
Description | Interview by CGTN |
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 | Public/other audiences |
Results and Impact | Increased profile of both Institute and The UK-China Centre of Excellence for Research on Avian Diseases (CERAD) |
Year(s) Of Engagement Activity | 2019 |
URL | https://newseu.cgtn.com/news/2020-01-28/British-and-Chinese-scientists-join-forces-to-fight-avian-di... |
Description | Pirbright village fair 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | This annual event, organised by Pirbright Parish Council and St. Michael & All Angels Church and hosted on the village green, offered an ideal occasion for the Institute to foster connections with the local community and ignite their interest in cutting-edge scientific research. This year's theme was 'Around the World' and included stalls and activities to reflect as many different countries and cultures as possible. The Institute's stall featured various engaging activities. Attendees, young and old had the opportunity to shake and reassemble virus models, swab Henrietta the hen to determine her health status, observe Culicoides nubeculosus midges in a display net, and examine midge larvae and pupae under a microscope for a closer inspection. |
Year(s) Of Engagement Activity | 2023 |
URL | https://thebull.pirbright.ac.uk/Interact/Pages/Content/Document.aspx?id=7311&SearchId=208907 |
Description | School visit (Tilingborne) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Stimulating increased interest in science and research |
Year(s) Of Engagement Activity | 2019 |
Description | School visit (Woking) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Stimulating increased interest in science and research |
Year(s) Of Engagement Activity | 2019 |
Description | Science Festival (Cheltenham) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Stimulating increased interest in science and research |
Year(s) Of Engagement Activity | 2019 |