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Novel single-cells omics and microfluidics approaches to tackle antimicrobial resistance

University of Exeter - College of Life and Environmental Sciences

Qualification Type: PhD
Location: Exeter
Funding for: UK Students, EU Students
Funding amount: BBSRC SWBio DTP funded CASE studentship available for September 2022 entry. The studentship will provide funding of fees and a stipend which is currently £15,609 per annum for 2022-23, on a full time basis.
Hours: Full Time
Placed On: 25th October 2021
Closes: 6th December 2021
Reference: 4289

We cannot see bacteria but there are around ten trillion of them in us or on us, thus ten times more the number of our own cells. Many bacteria are beneficial for us, some however, can cause infectious diseases such as meningitis or pneumonia. Indeed, bacterial infections are one of the leading causes of death worldwide and are estimated to lead to 300 million deaths by 2050.     

Antibiotics save millions of lives combatting infectious diseases. However, several bacteria, particularly those having a double membrane that makes them more impermeable, are resistant to antibiotic treatment. Therefore, we urgently need to develop strategies to overcome the current impasse by enhancing the accumulation of antibiotics near their bacterial targets, for example by using combination therapies with multiple antibiotics (Nature 559, 259, 2018).    

In order to understand the biological mechanisms underlying antibiotic uptake and efflux in Gram-negative bacteria, you will use a novel microfluidic technology that has recently been developed in Dr Pagliara’s team at the Living Systems Institute, University of Exeter (BMC Biol. 15, 121, 2017; Lab Chip 20, 2765 2020; RSC Chem. Biol. 1, 395, 2020). You will work in collaboration with the team of Dr Blaskovich at the University of Queensland, and Dr Serpi, University of Cardiff, to synthesise fluorescent derivatives of commonly used antibiotics and novel antibiotics, respectively.     

Combined with a fluorescence microscope, these microfluidic devices and fluorescent probes will allow you to measure antibiotics entering or exiting individual bacteria as well as measuring the efficacy of these compounds in killing bacteria. You will then apply omics approaches to identify genes and proteins that allow individual bacteria to avoid antibiotic accumulation.     

Using this knowledge and bioinformatics you will identify compounds that help antibiotics to enter and kill individual bacteria. The latter work will be carried out under the supervision of Prof Tsaneva-Atanasova. This project also offers the possibility for a placement at the Defence Science and Technology Laboratory where you will test newly identified combination therapies in simple infection models, such as the wax moth Galleria mellonella.    

Over the past ten years, single-microbe research has taken off around the globe engaging teams of scientists from different disciplines. As part of our battle against antibiotic resistance, by studying antibiotic uptake and efflux in single bacteria your project will provide crucial novel knowledge for the development of new antibacterial therapies and a better use of existing ones. 

Eligibility 

To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria. 

A fully-funded four year SWBio DTP studentship will cover 

  • a stipend* at the standard Research Council UK rate; currently £15,609 per annum for 2022-23
    •    research and training costs 
    •    tuition fees (at the standard Research Councils UK rate) 
    •    additional funds to support fieldwork, conferences and a 3-month internship 

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.  Any further queries in relation to residency must be directed to the institution that you are applying to. 

* An enhanced stipend is available for students with a recognised veterinary degree qualification (£24,090 per annum for 2022-2023). There may also be enhanced stipends associated with projects that have a CASE partner (highlighted as *CASE in the project lists). 

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