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EASTBIO A novel synthetic biology approach towards anti-bacterial cell therapy


   School of Biological Sciences

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  Dr E Cachat, Dr M Moule  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Project Description

With the rising threat posed by antimicrobial resistance and the slow pace at which new antibiotics are being developed, never has the need for new anti-bacterial treatment strategies been more pressing. We could envisage a future where, as an alternative to antibiotic therapy, our immune cells are engineered to seek-and-destroy specific bacterial species, much like CAR T cells are engineered to sense and respond specifically to cancer cells1. As a first step towards this goal, this project aims at harnessing recent advances in the field of synthetic biology to engineer mammalian cells capable of ‘sensing’ bacterial pathogens.

Synthetic biology applies the engineering principles of modularity and standardisation to construct new and improved biological systems. It strives to make the engineering of biology easier and more predictable, and already enables control over complex cellular behaviours in bacteria and yeast. The field is currently making great progress at extending this level of control to mammalian cells, bringing novel synthetic systems into the clinic2. By repurposing existing receptor architectures3, we will develop novel signalling circuits in mammalian cells that endow them with artificial bacteria-sensing functions. In the first instance, cells will be engineered to detect lab strains like Escherichia coli or Bacillus subtilis as a proxy for infectious bacterial cells. After this proof of concept stage and as a step further towards anti-bacterial cell therapy, mammalian cells will be engineered to detect - and eventually destroy - pathogens such as Pseudomonas aeruginosa or Staphylococcus aureus. The pathogen-sensing cells engineered in this project might also be used to study the cellular interactions taking place between bacteria and host cells during bacterial infections.

Training:

Within this project, the student will receive training in general scientific research skills and analytical methods, but also acquire specific skills in molecular and synthetic biology.

Student attributes:

You should enjoy working as part of a team, show an aptitude towards learning new techniques and be enthusiastic about- /show curiosity towards- synthetic biology. Other attributes: good presentation & communication skills, previous experience in cell culture would be a bonus.

https://www.ed.ac.uk/profile/elise-cachat

https://www.ed.ac.uk/profile/dr-maddie-moule

The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity

The “Institution Website” button will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership http://www.eastscotbiodtp.ac.uk/how-apply-0
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate (£17,668 annually in 2022) and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants, however any Visa or Health Insurance costs are not covered. UKRI eligibility guidance: Terms and Conditions: https://www.ukri.org/wp-content/uploads/2020/10/UKRI-291020-guidance-to-training-grant-terms-and-conditions.pdf International/EU: https://www.ukri.org/wp-content/uploads/2021/03/UKRI-170321-InternationalEligibilityImplementationGuidance.pdf

References

1. Wu, MR., Jusiak, B. & Lu, T. Engineering advanced cancer therapies with synthetic biology. Nat Rev Cancer 19, 187–195 (2019). https://doi.org/10.1038/s41568-019-0121-0
2. McNerney, M.P., Doiron, K.E., Ng, T.L. et al. Theranostic cells: emerging clinical applications of synthetic biology. Nat Rev Genet (2021). https://doi.org/10.1038/s41576-021-00383-3
3. Scheller, L. & Fussenegger, M. From synthetic biology to human therapy: engineered mammalian cells. Curr Opin Biotechnol 58,108-116 (2019). https://doi.org/10.1016/j.copbio.2019.02.023

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