EASTBIO: Development and characterisation of multi-cellular lung organoids for use in Bovine TB research at the University of Edinburgh

Despite decades of research, Bovine Tuberculosis (BTb) continues to cause significant animal welfare and economic issues globally. Caused by the intracellular bacterium Mycobacterium bovis, this zoonotic pathogen also infects and causes disease in humans and multiple animal species. Current diagnostic tools, vaccination and treatment options are not ideal; resulting in a continued reliance on the ‘test and cull’ strategy in the UK.

In this project, we aim to optimise the production of multi-cellular bovine lung organoids derived from bovine stem cells, and/or abattoir material, with the ultimate goal of reducing the numbers of live animals used in BTb research. These ‘lungs-in-a-dish’ (Archer et al. 2021, doi: 10.1186/s13567-021-00946-6) will be extensively characterised by comparing their cellular composition with bovine lung tissue, using a variety of approaches such as immunohistochemistry and quantitative RT-PCR techniques. Once the conditions for optimal organoid production are established, this project will be extended to study the interaction of M. bovis strains obtained from diverse locations within the UK which differ in virulence cattle, and in their ability to survive and replicate in bovine macrophages (Jensen et al. 2018, doi: 10.1128/IAI.00385-17; Jensen et al. 2020, doi: 10.1371/journal.pone.0222437). Cellular responses and the survival of the bacterium over time will be studied. In addition the interaction of infected cells with mucosal innate immune cells, which will be provided in co-culture, will also be explored. The information deriving from these studies will be invaluable in the development of more specific and sensitive diagnostic tools for BTb and provide important insights into the immunobiology of the lung: M. bovis interaction required for the smart design of future vaccination strategies.

This project would suit an enthusiastic, curiosity-driven student with an interest in molecular characterisation of host: pathogen interactions. The supervisory team have an excellent track record in PhD student supervision with a strong focus on personal development of the student, as well as the day-to-day training to develop the key experimental planning, data analysis and critical thinking skills of a well-rounded biological scientist. This project will provide the student with a variety of highly transferable technical skills in immunology, microbiology and cellular microbiology; including (but not restricted to) lung organoid culture, phenotypic characterisation of bovine immune cells, fluorescence microscopy, molecular biology techniques and specialist training to work with M. bovis at Containment Level 3.

• This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) www.eastscotbiodtp.ac.uk/how-apply-0

• EASTBIO Application and Reference Forms can be downloaded via www.eastscotbiodtp.ac.uk/how-apply-0

• Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [email protected]

• You should also ensure that two references have been send to [email protected]  by the deadline using the EASTBIO Reference Form

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees.  The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees.

There is a cap on the number of international students the DTP recruits.  It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our university.

Please refer to UKRI websiteand Annex B of the UKRI Training Grant Terms and Conditionsfor full eligibility criteria.

Closing Date: 16th December 2021