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EASTBIO Understanding a core cellular task: how cells maintain intracellular pH in alkaline stress


   School of Biological Sciences

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  Prof P Swain, Prof Teuta Pilizota  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

If the environment become alkaline, some pathogenic fungi undergo a change in shape that is a prelude to becoming virulent, but even in budding yeast – perhaps the most studied eukaryotic cell – we do not understand how cells survive the stress caused by alkalinity.

In this project, you will use a combination of microfluidics, time-lapse microscopy, molecular biology, and simple mathematical modelling to determine the strategy used by budding yeast to survive alkaline stress. We have developed technology that allows us to follow hundreds of single cells over time in environments that we are able to change in seconds. With a special fluorescent protein that reports intracellular pH, you will use this technology to expose cells to both rapid and gradual changes in alkalinity and phenotype cells both by their ability to maintain their intracellular pH and by their fitness through simultaneously measuring single-cell growth rates.

Cells modify intracellular concentrations of ions in this stress, particularly calcium, sodium, and phosphate, using signalling networks that are conserved in pathogens, such as the calcineurin pathway. By measuring levels of ion channels through tagging with fluorescent proteins and by determining the fitness of mutants with particular channels deleted, you will discover why budding yeast modifies ionic concentrations in this way and confirm your understanding by integrating the results into a mathematical model.

Finally, you will extend your results to the pathogen Candida glabrata by predicting and testing which deletions of ion channels make this yeast particularly vulnerable to alkaline stress.

https://swainlab.bio.ed.ac.uk

https://pilizotalab.bio.ed.ac.uk

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

How to Apply

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

Crane MM, Clark IB, Bakker E, Smith S, Swain PS. A microfluidic system for studying ageing and dynamic single-cell responses in budding yeast. PloS one. 2014 Jun 20;9(6):e100042.
Serra-Cardona A, Canadell D, Ariño J. Coordinate responses to alkaline pH stress in budding yeast. Microbial Cell. 2015 Jun 1;2(6):182.

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