PhD Studentship: Development of Oligonucleotide-Based Antimicrobials to Treat Burkholderia Pseudomallei Infections In The Lung (McArthur_U17FMH)

University of East Anglia - School of Norwich Medical School

Start Date: January 2018

Supervisor: Prof. Michael McArthur

Project description: The core technology is oligonucleotide-based antimicrobials that bind to and inhibit specific bacterial transcription factors to prevent expression of essential genes and so bacterial growth or virulence. These are referred to as Transcription Factor Decoys (TFDs) and consist of a short oligonucleotide containing the binding site covalently attached to a delivery head-group. We have demonstrated that the head-group can transfect a wide range of pathogenic bacteria, including Burkholderia pseudomallei. Delivery is via interaction with prokaryotic-specific anionic phospholipids such as Cardiolipin. By varying their sequences TFDs have been designed to treat MRSA, C. difficile and E. coli infections in various animal models following oral (to gut), intravenous and topical delivery. A Systems biology approach detect which transcription factors are induced in response to the stress caused by delivery and TFDs are designed to block this, so acting in synergy.

This project aims to design and validate a lead compound to treat respiratory infections caused by B. pseudomallei. Specific aims will be to: 1) optimise the structure of TFD conjugates for B. pseudomallei; 2) identify suitable TFD targets and validate in vitro (including in context of biofilms) and in Galleria mellonella survival models; 3) formulate for aerosol delivery to the lung.

Person specification: Acceptable first degree subject areas including Biochemistry, Cell/Molecular Biology, Cancer/Oncology, Nutrition, and Medicine. The standard minimum entry requirement is 2:1 or above or a Masters degree.

Funding notes: This PhD project is jointly funded by the Faculty of Medicine and Health Sciences and DSTL.  This studentship is funded for 3 years and comprises home/EU fees (£4,195), an annual stipend of £14,296 and £1000 per annum to support research training. International students are welcome to apply but will need to be able to meet the difference between Home/EU fees and Overseas Lab Based Project Fees (£18,000)

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South East England