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Understanding influenza-induced long-term changes to lung immunity

  • Full or part time
    Dr A Wack
  • Application Deadline
    Tuesday, November 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This 4-year PhD studentship is offered in Dr Andreas Wack’s Group based at the Francis Crick Institute (the Crick).

The Wack lab is interested in influenza virus infection, a disease of major public health impact whose severity ranges from mild cold-like symptoms to necessity of hospitalisation and death. We aim to understand what factors determine influenza severity and have studied the multifaceted interplay of gut microbiota, bacterial superinfection, pollution, airway epithelia and interferons in this disease [1-5].

Given its high prevalence, influenza afflicts individuals once or several times during their lifetime, and in the majority of cases, infection resolves without obvious long-term consequences. However, it is unknown whether the infection leaves an imprint in innate lung immunity that persists beyond full recovery. We have started studying this question in mice and have discovered that lung immune reactivity changes long-term after the end of influenza virus infection. This altered functionality is confined to a subset of lung immune cells called alveolar macrophages and corresponds to changes in their transcriptional profile and epigenetic landscape.

We are interested in understanding how general and long-lasting this phenomenon is: Do other infections or inflammatory and non-inflammatory insults to the lung always lead to the same stereotypical changes or does the type of initial lung insult condition which functional changes occur? Are other lung cell types involved in the changes we observe? We have so far observed changes to local immunity; does this correspond to changes in other organs or systemic changes? What are the underlying molecular and cellular mechanisms? Are similar infection-dependent changes detectable in humans? If over longer time periods, these changes in functionality disappear, what are the signals leading to this disappearance and who sends them?

To answer these questions, a vast range of techniques are in use at present: Extensive in vivo experimentation in genetically altered infection models and using lineage-tracing strategies; study of human immune cells; multiple –omics technologies to understand transcriptional, metabolic and epigenetic changes in lung immune cells; bioinformatic analysis and extensive comparison with existing datasets from human and murine immune cells; and extensive functional analysis of selected immune cell types in vitro. The excellent Crick core facilities render such multi-pronged approaches feasible. The PhD project will be collocated in one of these research areas. With these studies, we aim to understand better how a life-long biography of infections continually reshapes lung immunity in humans.

Candidate background
Candidates should be interested in immunity to infection and have in vitro and / or in vivo experience in this area. Applications from individuals with bioinformatics background or with interest and experience in epigenetic analysis would also be appreciated.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2020 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.


Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.


1. Crotta, S., Davidson, S., Mahlakoiv, T., Desmet, C. J., Buckwalter, M. R., Albert, M. L., . . . Wack, A. (2013)

Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.

PLOS Pathogens 9: e1003773. PubMed abstract

2. Davidson, S., Crotta, S., McCabe, T. M. and Wack, A. (2014)

Pathogenic potential of interferon αβ in acute influenza infection.

Nature Communications 5: 3864. PubMed abstract

3. Ellis, G. T., Davidson, S., Crotta, S., Branzk, N., Papayannopoulos, V. and Wack, A. (2015)

TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection.

EMBO Reports 16: 1203-1218. PubMed abstract

4. Villa, M., Crotta, S., Dingwell, K. S., Hirst, E. M. A., Gialitakis, M., Ahlfors, H., . . . Wack, A. (2016)

The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis.

Nature Communications 7: 12652. PubMed abstract

5. Bradley, K. C., Finsterbusch, K., Schnepf, D., Crotta, S., Llorian, M., Davidson, S., . . . Wack, A. (2019)

Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection.

Cell Reports 28: 245-256 e244. PubMed abstract

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