Genetic diversity in immune response

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Interaction of virus with the host is fundamental to initiate an infection and to complete a successful replication cycle, however, the outcome of this initiation depends up several factors of both virus and host origins. Among host responses, the most profound and first-line-of-defense is the induction of innate immune responses mediated by the central player, type I interferons (IFN). Although induction of IFNs is generic but the terminal actions can be host and pathogen specific. In this context, chicken is unique since even in the updated version of chicken genome, it appears that chicken lack kinase Tyk2, STAT2 and IRF9, which are crucial elements in JAK/STAT pathway (IFN signalling). However, interestingly, ectopic expression of duck RIG-I in chicken cells reconstituted the downstream signalling pathway, with higher induction of several interferon stimulated genes (ISGs), indicating the presence of potent mechanism of ISGs transcriptional regulation in chicken while apparently lacking IRF3 and RIG-I genes. It would therefore be interesting to study the ways chickens have evolutionarily adapted other compensatory mechanisms compared to ducks, turkeys and gees. Aims of my research activities include understanding the innate immune response in different avian hosts that range from sensing of viruses to terminal IFN effectors mediated by myriad interferon stimulated genes. Currently, I have established large-scale, genome-wide and high throughput screen platforms to investigate, both generically and specifically, the interaction of viruses with host immune responses and the ways viruses have adapted to circumvent these responses using proof-of-the-concept avian paramyxoviruses (different pathotypes of Newcastle disease virus).

Publications

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Góes LGB (2016) Genetic diversity of bats coronaviruses in the Atlantic Forest hotspot biome, Brazil. in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

 
Description Through this fellowship, novel genomics and proteomics methodologies have been developed, and are being applied to address the genetic diversity of innate immune genes in chicken and duck.

We identified new interferon in chicken and other avian species

We investigate the novel mechanisms of viral genome sensing in chicken
Exploitation Route Understanding the molecular mechanisms of differences in innate immunity between hosts of variable virus susceptibilities would help to devise better control measures and therapies.
Sectors Agriculture, Food and Drink

 
Description Bilateral BBSRC-FAPESP Research Grant: Dissecting Essential Roles of Chicken Interferon Stimulated Genes in the Pathobiology of Poultry Viruses
Amount £383,644 (GBP)
Funding ID BB/M008681/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2015 
End 09/2018
 
Description Brazil Partnering Award: Population genetic diversity of wild birds and its influence on virus evolution and biology
Amount £18,219 (GBP)
Funding ID BB/L026546/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2014 
End 06/2017
 
Description Construction of an interferon stimulatory gene mini-library for chiropteran species and assessment of the expression dynamics of bat interferon stimulated genes (baISGs)
Amount £15,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 03/2015 
End 04/2016
 
Description Emerging and Next Generation Vaccine Technologies Against Veterinary Viruses
Amount £43,000 (GBP)
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2016 
End 09/2016
 
Description Evasion of host innate immunity by Newcastle Disease Virus (NDV) and its pathogenic consequences
Amount £26,513 (GBP)
Funding ID BBS/E/I/00001991 
Organisation The Pirbright Institute 
Sector Academic/University
Country United Kingdom
Start 01/2015 
End 04/2017
 
Description Newton Fund, Institutional Links
Amount £230,000 (GBP)
Funding ID 172710323 
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2015 
End 09/2017
 
Description Preparedness for novel virus emergence from wild birds and bats: metagenomics-driven viromes and understanding innate immunity
Amount £220,000 (GBP)
Funding ID 172710323 
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 12/2017
 
Description Triple-Reporter Cell Lines for Screening of Antiviral and Viral Immune Modulator
Amount £6,000 (GBP)
Funding ID 2015/R2 (inc CNRS) 
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 05/2015 
End 06/2016
 
Description Avian Vaccines Malaysian Researchers 
Organisation Putra Malaysia University
Department Department of Pathology
Country Malaysia 
Sector Hospitals 
PI Contribution We have successfully organized a British Council funded workshop on Emerging and Next Generation Vaccine Technologies Against Veterinary Viruses at Institute of Bioscience (IBS), Universiti Putra Malaysia from 01 to 04 August 2016.
Collaborator Contribution Through this partnership, we have applied two research grants to work together in tackling infections in poultry.
Impact Two Funding Applied One Publication Online
Start Year 2016
 
Description Collaboration and Partnership With American Researchers 
Organisation University of Rochester
Department Neuromuscular Disease Center
Country United States 
Sector Academic/University 
PI Contribution To establish bases on system biology of avian immunity, collaboration was established with Luis Martinez-Sobrido.
Collaborator Contribution Researcher from Rochester are establishing mouse reporter cell lines and we at Pirbright are generating chicken reporter cell lines to be used for antiviral and virus pathogensis studies.
Impact We have devised the CRISPR/Cas9 strategy and are working to generate knockin cell lines in both institutions.
Start Year 2016
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation State University of Campinas
Country Brazil 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation University of Sao Paulo
Department Department of Virology
Country Brazil 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Partnership with Brazilian Researchers working on avian and bats immunity 
Organisation University of Surrey
Department Surrey Space Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Through Bats and Birds Research Network, we gathered a team of researcher who have interests or working on avian and bats innate immunity. All above-mentioned partners are now active members of the network and contributing significantly.
Collaborator Contribution We have obtained two funding, one from BBSRC and one from British Council to investigate the role of virus induced innate immunity and dynamics of viruses in these hosts. Brazilian participants are mainly responsible to collect samples, based on their extensive field experience and British partners are involved in the analysis and interpretation of the outcome.
Impact Workshop on Birds and Bats at University of Surrey, June 2016 Poultry Health Course at Pirbright Institute, April 2017 Visit of Brazilian and British Partners to laboratory facilities Virtual Meeting to Discuss and Plan the Collaborations Mutual Funding and Research Articles
Start Year 2015
 
Description Avian Genetics and Immunity (University of Surrey) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Symposium on Avian Genetics and Immunity is being to engage international audience with interests on avian genetics and immunity
Year(s) Of Engagement Activity 2017
URL http://geneticsandimmunity.com
 
Description Birds and Bats Workshop (University of Surrey) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact It was organised to bring together researchers from Brazil and UK to discuss the current advances in bats and bird immunity and virology
Year(s) Of Engagement Activity 2016
URL http://birdsandbats.net
 
Description Invited Talk at Rochester Medical University New York, USA: Antiviral Potential of Chicken IFIT5 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact During the talk, several questions were asked and possibilities for the future collaboration was assessed. Taking on from there, we are planning a joint USA-UK application in coming call from different councils.
Year(s) Of Engagement Activity 2017
 
Description Invited Talk in Harbin Veterinary Research Institute, China: Avian Functional Genomics and Innate Immunity 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact In this invited talk, several stakeholders were present and we agreed to apply for a funding together through Newton Fund-BBSRC call on Swine and Poultry Diseases in Developing Countries. Although the application was unsuccessful, a strong link was established.
Year(s) Of Engagement Activity 2017
 
Description Poultry Health Course (Pirbright) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The course is organised for participants from Brazil to understand the current advances in poultry diseases.
Year(s) Of Engagement Activity 2017
URL http://www.poultryhealthcourse.com/
 
Description Presentation in GARAD-2018 in Vietnam: Potential of chicken IFIT5 in Establishing Antiviral State 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact In the Global Alliance for Research on Avian Diseases 2018, I have presented our work on current understanding of IFIT5 mediated antiviral potential in avian species.
Year(s) Of Engagement Activity 2018
URL http://www.theeventsportal.com/GARAD-2018/3/Home
 
Description UK-Malaysia Vaccinology Workshop (Malaysia) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This workshop aimed to build long-term and sustainable links between scientists in the UK and Malaysia working on/have interests in veterinary vaccines. This workshop has encouraged early career researchers from veterinary, biological and social sciences to understand the ever-increasing threats to global food security from infectious animal diseases and their control using next generation vaccine strategies.
Year(s) Of Engagement Activity 2016
URL http://ukmalaysiaworkshop.co.uk/