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


School of Biological Sciences

Prof P Swain , Prof Teuta Pilizota Wednesday, January 06, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

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

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 baker’s 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 extracellular pH and phenotype cells 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 the numbers of ion channels through tagging these channels with fluorescent proteins and by determining the fitness of mutants with particular channels deleted, you will discover why baker’s yeast modifies ions in this way and confirm your understanding by integrating the results into a mathematical model of cell growth.

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. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process.


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website. This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants. Please refer to UKRI website (View Website) and Annex B of the UKRI Training Grant Terms and Conditions (View Website) for full eligibility criteria.

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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