Technology development for in situ imaging of microbial cultures

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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 (teuta.pilizota@ed.ac.uk)