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MSc by Research Programme: Identifying key regulators of growth-arrested states in Pseudomonas aeruginosa


About This PhD Project

Project Description

This course allows you to work alongside our world renowned experts from the School of Life Sciences and gain a ’real research’ experience. You will have the opportunity to select a research project from a variety of thematic areas of research.

You will be part of our collaborative working environment and have access to outstanding shared facilities such as microscopy and proteomics. Throughout your year, you will develop an advanced level of knowledge on your topic of interest as well as the ability to perform independent research in the topic area. Alongside basic science training in experimental design, data handling and research ethics, we will help you to develop skills in critical assessment and communication. This will be supported by workshops in scientific writing, presentation skills, ethics, laboratory safety, statistics, public engagement and optional applied bioinformatics.

The period of study is one year full-time or two years part-time research, which includes two months to write up the thesis. Please apply via the UCAS postgraduate application form: https://digital.ucas.com/courses/details?coursePrimaryId=c735d826-42b6-ca1f-50db-2a3ac6f68718

In natural environments, including some infections, bacteria are forced to spend long periods of time in growth-arrested states because they are limited for an essential nutrient. Under these conditions, they are highly tolerant of antibiotics, since these drugs target growth-related processes that are generally not being utilised in growth arrest. Intriguingly, previous work has found that P. aeruginosa cells that are forced into growth-arrested states can still synthesize new proteins at very low rates, and that the proteins they preferentially synthesize include several enhancers of transcription and translation. These findings suggest that growth-arrested cells are still regulating their activities and potentially capable of responding to their environment. A better understanding of how growth-arrested cells can sense and respond to their environment could lead to new insights into how to target them with novel antimicrobial therapeutics. There is a need for novel strategies to treat P. aeruginosa specifically, because it can cause infections in immunocompromised patients that are very difficult to treat, and more generally to treat all bacterial infections because resistance to existing antibiotics is a growing problem.

To identify key regulators, this project will use a genetic screening method called Tn-Seq. This method involves making a library of tens of thousands of bacterial mutants, competing them against each other under a condition of interest, and then identifying the mutants that fare the best and those that fare the worst. We will subject our mutant pool to growth-arrested conditions in which a variety of additional mild stresses are encountered, thus selecting for mutants that are best able to respond to changing conditions despite extreme resource limitation. After identifying candidate genes of interest, we will conduct follow-up experiments on one or two of them to gain a better understanding at a molecular level of how they impact regulation during growth arrest.

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