Back to search results

PhD Studentship: The Role of Bacterial Membrane Potential in Tuberculosis Persistence and Regrowth

London Interdisciplinary Biosciences Consortium - Pathobiology and Population Sciences, Royal Veterinary College

Qualification Type: PhD
Location: London
Funding for: UK Students, EU Students, International Students
Funding amount: £20,622 per annum
Hours: Full Time
Placed On: 23rd October 2023
Closes: 10th January 2024

This project is an industrial CASE studentship based at the Royal Veterinary College in collaboration with start-up company (Cytecom) based in Warwick. The project will investigate the biochemical, genetic, and electrophysiological pathways underlying persistent infections in tuberculosis (TB). Tuberculosis, caused by the bacterium Mycobacterium tuberculosis (Mtb), is the highest cause of mortality by a single infectious agent and kills 1.5 million people annually. Treatment of TB in humans is with lengthy, toxic, multidrug regimens and the increasing emergence of drug resistant TB is a global concern. Mtb is able to enter a physiological persistent state which is phenotypically resistant to antimicrobials.

Persistent states in many bacterial species is associated with a phenotype known as the small colony variant (SCV). The clinical importance of SCVs is highlighted by their isolation from patients with persistent, recurrent infections. SCVs show delayed growth and defects in community behaviours such as biofilm formation and cell-cell signalling. We have recently used CRISPRi to silence a putative haem synthase (HAS) in a non-pathogenic model of Mtb (Mycobacterium smegmatis) and observed a SCV phenotype. In this project we explore this phenotype using a combination of molecular microbiology, electrophysiology, and innovative mathematical modelling.

The aim of this project is to investigate persistent phenotypes in TB and measure impacts on global gene expression, membrane potential and quorum sensing behaviours. We hypothesise that silencing of the mycobacterial HAS leads to inhibition of the respiratory chain and a reduction in membrane potential. This reduction in membrane potential inhibits cell to cell communication behaviours and causes a delay in regrowth classically described in SCVs. This project will explore the novel concept that electrical signalling plays a role in allowing bacteria to sense their environment and communicate with one-another. A concept that is gaining traction in model organisms.

This project offers training in molecular microbiology such as CRISPRi gene silencing, targeted mutagenesis approaches and global transcriptomics. It offers training in mathematical modelling as neuron-firing models will be applied and modified to interpret changes in bacterial membrane potential in different physiological states.

We value your feedback on the quality of our adverts. If you have a comment to make about the overall quality of this advert, or its categorisation then please send us your feedback
Advert information

Type / Role:

Subject Area(s):

Location(s):

PhD tools
 

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Ok Ok

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Manage your job alerts Manage your job alerts

Account Verification Missing

In order to create multiple job alerts, you must first verify your email address to complete your account creation

Request verification email Request verification email

jobs.ac.uk Account Required

In order to create multiple alerts, you must create a jobs.ac.uk jobseeker account

Create Account Create Account

Alert Creation Failed

Unfortunately, your account is currently blocked. Please login to unblock your account.

Email Address Blocked

We received a delivery failure message when attempting to send you an email and therefore your email address has been blocked. You will not receive job alerts until your email address is unblocked. To do so, please choose from one of the two options below.

Max Alerts Reached

A maximum of 5 Job Alerts can be created against your account. Please remove an existing alert in order to create this new Job Alert

Manage your job alerts Manage your job alerts

Creation Failed

Unfortunately, your alert was not created at this time. Please try again.

Ok Ok

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

 
 
 
More PhDs like this
Join in and follow us

Browser Upgrade Recommended

jobs.ac.uk has been optimised for the latest browsers.

For the best user experience, we recommend viewing jobs.ac.uk on one of the following:

Google Chrome Firefox Microsoft Edge