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EASTBIO Using ribosome profiling to identify novel mechanisms underlying the pathogenesis of bovine tuberculosis


Project Description

Royal (Dick) School of Veterinary Studies / The Roslin Institute

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), represents major threats to livestock and human health worldwide. The principal route of M. bovis infection is via the inhalation of infectious aerosols into the lung tissues, especially the alveolus. Alveolar macrophages (AMs), in the lungs, are the first cells that phagocytose the inhaled bacteria and provide the initial replication niche in the host1. The molecular mechanisms induced immediately after the inhaled Mycobacteria interacts with AMs determines whether the infection results in bacterial eradication, containment and asymptomatic infection, or unrestricted replication and active TB1,2. Yet, the mechanisms underpinning early bovine AM-bacteria encounters are largely unknown despite their potential to equip us with tools to combat bTB. Recent studies have shown that innate immune cells such as AMs, respond rapidly to drastic changes in their environment by modulating the completement of synthesised proteins, rather than mRNA3. This make sense since direct modulation of protein synthesis – the direct effectors of cellular function – provides a faster and more direct means for adjusting cellular protein levels compared to de novo mRNA synthesis and processing. Our preliminary data shows that bovine macrophages respond to biotic stress by modulating mRNA translation (translational control). We hypothesise that the early AM response to M. bovis is modulated by a set of translationally regulated genes induced immediately after AM-M. bovis encounter.

In this project, the student will apply the state-of-the-art ribosome profiling technology, in combination with well-established bioinformatics and immunological tools, to monitor temporal genome-wide changes in mRNA translation to model the signalling pathways underpinning AM-bacteria encounters and, identify novel genes that can be exploited in host-directed therapies against BTB

The student will acquire interdisciplinary training on immunology, microbiology, functional genomics and bioinformatics. The Roslin Institute has several research groups and students studying various aspects of infectious diseases, which will offer the successful student ample opportunities for academic and social growth. The student will also have opportunities to interact with scientist studying livestock infectious diseases in low and middle-income countries at the Centre for Tropical Livestock Health and Genetics.

For further information please contact:
Dr Musa Hassan () or Prof. Jayne Hope. ()

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

Funding Notes

Applications:
Completed application form along with your supporting documents should be sent to our PGR student team at

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh, Royal (Dick) School of Veterinary Studies and the Roslin Institute project should be returned to by the closing date: 5th January 2020.

It is your responsibility to ensure that references are provided by the specified deadline.
Download application and reference forms via:
View Website

References

1. Cohen, S. B. et al. Alveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination. Cell Host Microbe (2018). doi:10.1016/j.chom.2018.08.001
2. Cadena, A. M., Flynn, J. L. & Fortune, S. M. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome . MBio (2016). doi:10.1128/mbio.00342-16
3. Su, X. et al. Interferon-gamma regulates cellular metabolism and mRNA translation to potentiate macrophage activation. Nat Immunol 16, 838–849 (2015).

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