Technology Development for In-Situ Imaging of Microbial Cultures

University of Edinburgh

School of Biological Sciences

Project Description

The current standard for estimating the growth of bacterial cultures, optical density (OD) measurements, no longer provides sufficient information needed for academic research, industrial biotechnology applications, and pharmacological work on antimicrobial resistance. As a matter of fact, all these sectors increasingly require accurate information on cell morphology, which is now recognized as an early indicator of host-cell physiological changes that have a negative effect on the product yield. Additionally, specific shape changes point to the underlying molecular mechanism that causes them, enabling more efficient troubleshooting of product development pathways. For example, production of recombinant proteins in Escherichia coli affects cells’ intracellular pressure, forcing the cells to inadvertently leak the product and other cellular content during fermentation. An early indication of cellular pressure changes is increase in the cells size and a characteristic change in cell shape that subsequently leads to cell blebbing, which, if detected early, can be accounted for. Furthermore, imaging cells during production can enable improved analysis of product accumulation (such as early detection of inclusion bodies) simultaneously with morphological information, which offers the potential to reveal the molecular pathway that causes it.

To overcome this challenge, as part of this project you will develop a cell counter/imager device. The global cell counting and high-throughput imaging market is currently focused mainly on mammalian cells, whereas here we will focus on imaging microbial cells. The task of imaging (and counting via imaging) of microbial, and in particular bacterial cells, is non-trivial due to their small size, extensive size changes (up to 100 times), as well as the fact that bacteria can swim. You will work in an interdisciplinary team composed of physicists, engineers, biotechnologists and microbiologists to succeed in this project, and will learn from their extensive expertise in customized microscopy and microbiology. Since this project has commercial potential, details of day to day work are confidential. Please email Teuta directly to speak about the project timeline and specific techniques involved ([email protected]) The project will be based in Pilizota lab (pilizotalab.bio.ed.ac.uk/) in collaboration with Menolascina lab. You will have the opportunity to work as part of the Synthetic and Systems Biology Centre at University of Edinburgh and interact with academic labs working on themes of relevance for this project.

The project is part of IBioIC Doctoral Training Centre, please visit their webpages to familiarize yourself with training opportunities and requirements this will entail ibioic.com/ibioic_ctp/d6/ Furthermore, as part of the project you will have the opportunity to take a 6-month placement at OGI Bio, University of Edinburgh’s spinout company.

Eligibility Requirements

To be eligible for this project (a) your background should be in engineering (electrical, mechanical, biomedical), physics or biotechnology (providing that your degree covered sufficient number of courses in physics and engineering), and (b) you should be UK/EU (with 3-year residency in UK prior to the application) student.

Application Process

Use the Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
Application Deadline: 31 January 2021, for a start date up until 30 September 2021.

References

Stevenson K, et al Sci. Rep. 2016;6:38828
Pilizota T, et al, Biophys J. 2007 93:264-275
Rosko J, et al PNAS 2017; doi: 10.1073/pnas.1620945114

To apply for this PhD, please use the following application link: https://apps.bio.ed.ac.uk/pgr/checklist/project/1009

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