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  Mechanisms of induction of protective lung tissue resident memory cells against influenza


   Pirbright Laboratory, Surrey, Outer London

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  Dr E Tchilian, Prof Christine Rollier  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Influenza is a global health threat to humans and livestock and animal influenza viruses are the CDC’s top zoonotic pathogen. There is a critical need to develop vaccines that provide broad protection and decrease the need for annual immunisation.

We have established a powerful pig influenza model to study immunity to influenza. Pigs are a natural host for the same subtypes of influenza virus as humans and have the same distribution of sialic acid receptors in their respiratory tract. The pig is immunologically, physiologically and anatomically more similar to humans than small animals.

Lung tissue-resident memory T and B cells (TRM and BRM) are critical for cellular immunity to influenza and other respiratory pathogens. TRM and BRM are most effectively induced by natural infection or mucosal delivery of vaccines. However the factors necessary for their generation and maintenance are not well understood, but both the method of antigen administration and the nature of the antigen itself may play a crucial role. In this project we shall investigate the generation and properties of TRM and BRM induced by H1N1pdm09 influenza infection or mucosal immunisation with adenoviral vectored vaccine expressing influenza internal (nucleoprotein) and external (hemagglutinin) proteins.

The student will have the opportunity for the first time to dissect the mechanisms of induction of TRM and BRM in a large natural host animal model and to establish their role in immunity to influenza. The student will:

1. Define the phenotype and function of TRM and BRM following infection or immunisation.

2. Characterise the inductive microenvironment in the lung following infection or immunisation.

3. Adopt an unbiased data driven transcriptomic approach to identify TRM and BRM from well protected or poorly protected animals.

The student will be exposed to the unique scientific environment in Pirbright and Surrey which offer complementary skills and facilities. The student will also have the opportunity to collaborate with human immunologists from Oxford and Imperial College London. The proposed studies will determine whether alterations in the mode of priming affect the nature of the TRM and BRM response. This will be a crucial step in the more rational development of novel vaccine strategies for influenza and other respiratory diseases.

TO APPLY: Full details of how to apply can be found on our website How to apply | The Pirbright Institute

For informal enquiries regarding this project please contact the project supervisors.

For enquiries regarding eligibility and the application process please email [Email Address Removed]

For Home student eligibility guidelines, please refer to the UKRI Full Eligibility Criteria (Annex One): UKRI-030221-Guidance-International-Eligibility-Implementation-training-grant-holders-V2.pdf

Biological Sciences (4) Veterinary Sciences (35)

Funding Notes

This is a fully funded studentship open to UK nationals. Eligible students will receive a minimum stipend of £15,609 pa plus a cost of living allowance £2,200 pa. University tuition fees will be paid at the Home rate. EU and international applicants are welcome to apply, however from 1st August 2021, EU and International students will be liable for tuition fees at the international rate and must be able to fund the difference between Home and Overseas tuition fees themselves. For Home student eligibility guidelines, please refer to UKRI Full Eligibility Criteria (Annex One) - link above.

References

1. Martini V et al. Simultaneous Aerosol and Intramuscular Immunization with Influenza Vaccine Induces Powerful Protective Local T Cell and Systemic Antibody Immune Responses in Pigs (2021). J Immunol. 206:652-663; doi: 10.4049/jimmunol.2001086
2. Holzer B et al. Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans (2021). PloS Pathogens 17(3):e1009330. doi: 10.1371/journal.ppat.1009330
3. Canini L et al. Timelines of infection and transmission dynamics of H1N1pdm09 in swine (2020). PLOS Pathogens, 16(7): e1008628; doi: 10.1371/journal.ppat.1008628
4. Martini V et al. Distribution of droplets and immune responses after aerosol and intra-nasal delivery of influenza virus to the respiratory tract of pigs (2020). Frontiers in Immunology 11:594470; doi: 10.3389/fimmu.2020.594470
5. McNee A et al. Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms (2020). J Immunol. 205(3):648-660; doi: 10.4049/jimmunol.2000429