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A time-resolved analysis of the molecular events underlying bovine innate immune activation: Insights from bovine macrophage response to Mycobacterium bovis

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  • Full or part time
    Dr Musa Hassan
    Prof J Hope
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Bovine tuberculosis (bTB) is a major animal health problem world-wide and a serious zoonotic threat in developing countries. Developing new tools to tackle bTB requires a deeper molecular understanding of host interactions with Mycobacteria bovis (M. bovis), the bacteria that causes bTB. M. bovis, infections occur mainly via the inhalation of infectious bacilli. In the lungs, the bacteria are first phagocytosed and replicate in alveolar macrophages (AMs) before disseminating to other host cells[1]. Thus, the mechanisms that define the early bacteria-AM interactions determine whether the infection results in bacterial eradication, containment and asymptomatic infection, or unrestricted replication and active bTB[1,2]. Despite the potential to equip us with tools to tackle bTB, the mechanisms underpinning early bovine AM-M. bovis interactions are largely unknown.

Here, we will use well-established molecular biology, high throughput sequencing, and computational protocols to identify and quantify the genes that are turned on, and determine which of these genes that are eventually translated into proteins, in the course of AM-M. bovis interactions. Emperical data show that when cells are stressed, they regulate the complement of synthesised proteins, the direct effectors of cellular processes, by altering the rate of translating available mRNAs into proteins (translation control), rather than synthesising new mRNAs[3]. As the first line of defense against invading pathogens, innate immune cells such as AMs, must respond rapidly to eliminate pathogens and/or innitiate long-term adaptive immunity. We postulate that translation control significnatly impact the impact the early and long-term adaptive AM resoponses to M. bovis. Therefore, by profiling mRNA and protein synthesis in AMs exposed to different strains of M. bovis, we will discover which cattle proteins are essential for eliminating avirulent M. bovis and what goes wrong when they are exposed to pathogenic bacteria. We will then use this information to inform in vivo AMs functional assays.

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 LMICs at the Centre for Tropical Livestock Health and Genetics.

For further information please contact:
Dr. Musa Hassan ([Email Address Removed])
or
Prof. Jayne Hope ([Email Address Removed])

Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships

Funding Notes

3.5 year PhD
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

All applicants should also apply through the University's on-line application system for September 2020 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=831

References

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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