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Using Nanotechnology to address antibiotic resistance


School of Biosciences

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Prof Tim Dafforn , Prof D Roper No more applications being accepted Funded PhD Project (UK Students Only)
Birmingham United Kingdom Biochemistry Bioinformatics Biophysics Microbiology Pharmaceutical Chemistry Structural Biology

About the Project

Bacterial antibiotic resistance is a major global health challenge (10 million deaths a year are predicted by 2050 at a cost of £66 trillion). More than 60% of therapeutic drugs target are membrane proteins but historically it has been exceptionally difficult generally to produce stable samples in any quantity for study and drug discovery. This has greatly limited the exploitation of membrane proteins generally for developing conventional drugs as well as for future healthcare technologies.

We have developed a nanoparticle approach to this problem by combining an amphipathic polymer (Styrene-co-Maleic Acid; SMA) and phospholipid bilayers which inserts into native phospholipid membranes and extracts 10 nm diameter discs (SMALPs) of the membrane. Uniquely this enables membrane proteins to be produced complete with the lipid environment that surrounds them and stabilises the protein. This means that the protein can be studied using a wide range of techniques including:

1.    Ligand binding assays and characterisation including Surface Plasmon Resonance

2.    Molecular structural techniques which may include X-ray Crystallography and Cryo-Electron Microscopy

This iCASE project is a collaboration between Professor Tim Dafforn at the University of Birmingham and Professor David Roper at the University of Warwick with industrial partner Defence Science Technology Laboratory (DSTL) at Porton Down.  

Our aim is to use the SMALP method to:

1.    Extract and purify membrane proteins that DSTL has identified as potential targets for novel antimicrobial therapies

2.    Investigate the structure and function of these extracted membrane proteins

3.    Develop ligand binding assays that will underpin a programme of drug discovery

At the end of the project, you will be skilled in membrane protein biochemistry and have experience in cutting edge methods used to study these proteins. You will also have experience of working in laboratories at DSTL and the partnering Universities.


Funding Notes

Funding is through an EPSRC iCASE studentship with Birmingham, Warwick and the Defence Science Technology Laboratory

References

Lee et al. Sci Rep. 2019 Dec 10;9(1):18712. doi: 10.1038/s41598-019-54999-x.
Teo et al. Sci Rep. 2019 Feb 12;9(1):1813. doi: 10.1038/s41598-018-37962-0.
Parmar et al. Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):378-383. doi: 10.1016/j.bbamem.2017.10.005. Epub
Lee et al. Nat Protoc. 2016 Jul;11(7):1149-62. doi: 10.1038/nprot.2016.070
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