Prof S Gordon, Prof David MacHugh
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
A four-year PhD studentship in Mycobacterium bovis-specific virulence mechanisms and host-pathogen interaction is available at the Molecular Microbiology Laboratory at the University College Dublin. Applicants should have a 2.1 honours degree or higher in Microbiology, Immunology, Genetics/Genomics, Cell Biology, Biochemistry or a cognate discipline.
Tuberculosis (TB) is a devastating disease of humans and animals. Mycobacterium bovis, which causes bovine tuberculosis, is a major zoonotic pathogen and causes billions of annual losses to global agriculture. Fundamental gaps in our knowledge of host-pathogen interaction in TB hinder the development of new vaccines and diagnostics to help combat the disease. In this project we will address these knowledge gaps by exploring key M. bovis virulence adaptations, building on comparative analyses between M. bovis and the human pathogen Mycobacterium tuberculosis that show the latter to be attenuated in the bovine host.
The project will involve the construction of recombinant mycobacteria with potential virulence factors inactivated, and then using these recombinants in macrophage infections to explore how the innate response to infection is modulated. A key component will be the application of transcriptomics and related bioinformatics analyses to define the macrophage response to infection.
The research project will be carried out within a ‘One Health’ framework, leveraging information from parallel genomics studies of host-pathogen interactions in human tuberculosis caused by Mycobacterium tuberculosis. This information will feed into the development of novel biomarkers of TB infection.
The successful applicant will join a group of researchers investigating bovine and human tuberculosis, and will have access to outstanding UCD research facilities. The student will be co-supervised by Profs Stephen Gordon and David MacHugh and will be enrolled in the UCD Thematic PhD Programme in Infection Biology (www.ucd.ie/infectbio), and will include advanced training in microbiology, immunobiology, computational biology and bioinformatics.
Funding Notes
Four-year Science Foundation Ireland (SFI) funded position, €18,000 stipend per annum, postgraduate fees funded separately by the project. Only available for EU students.
References
Correia C.N., et al. (2017) Circulating microRNAs as Potential Biomarkers of Infectious Disease. Front. Immunol. 8, 118.
Farrell D., et al. (2016) Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis. Microbial genomics 2, e000071.
Healy C., et al. (2016) The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase. Tuberculosis (Edinb) 97, 154-62.
Nalpas N.C., et al. (2015) RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli. Sci. Rep. 5, 13629.
Vegh P., et al. (2015) MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking. Tuberculosis 95, 60-7.