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EASTBIO: Investigating the role of bacterial mechanosensitive channel periplasmic domains in cell survival.

  • Full or part time
    Dr S Miller
    Dr Teuta Pilizota
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Supervisors:

Dr Samantha Miller (University of Aberdeen)
https://www.abdn.ac.uk/people/sam.miller/

Dr Teuta Pilizota (University of Edinburgh)
https://www.ed.ac.uk/profile/teuta-pilizota

Bacteria have evolved specific molecules and mechanisms to survive their dynamic environment. Understanding these fundamental processes are important not only for enhancing our knowledge but also potentially for future treatments of disease and enhancing biotechnological processes such as in synthetic biology. In this project we will examine the function of a periplasmic domain found in a unique subclass of bacterial mechanosensitive channels in bacterial survival. We hypothesise these domains have evolved to aid bacterial cell survival in specific environmental transitions by coupling their function to that of a mechanosensitive channel. The project will combine microbial and biochemical techniques with biophysical approaches in bacterial cells.

Mechanosensitive (MS) channels are ubiquitous throughout life kingdoms. They are gated by changes in membrane tension and in higher organisms involved in processes such as hearing, balance and pain perception. In bacterial cells they are required to survive hypoosmotic shocks, such as transfer from a high salt to a low salt environment. In this situation, unless the MS channels open to release cell solutes, bacterial cells lyse and die. The MscL and MscS channels are the principal channels involved in this response. They have been extensively studied at the biochemical, structural and genetic level in Escherichia coli. Bacterial strains have multiple MscS family members, for example E.coli has 6 members. The family are related by their common core domain structure but are distinguished by additional domains, often of unknown function. This diversity of structure and associated potential for variations in function is not well understood. Periplasmic domains are one major variation. These channels can have high similarity in their membrane domains, but their periplasmic domains can be unique. The periplasmic domains appear to have little precedent in the genome sequence database, although some are related to solute binding proteins of transporters. In this project we will investigate the function of these domains, exploring their role in bacterial stress responses and cell survival. We will build on our unpublished data and existing tools (materials and approaches) together with the complementary expertise and experience of the supervisors. This project would suit a biophysicist interested in learning biological and biochemical techniques or biochemists and microbiologists interested in learning biophysical techniques.

Application Procedure:
http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at . Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to .

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. Queries on eligibility? Email Alison McLeod ().

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

Rasmussen T, Rasmussen A, Yang L, Kaul C, Black S, Galbiati H, Conway SJ,
Miller S, Blount P, Booth IR. (2019) Interaction of the Mechanosensitive Channel, MscS, with the Membrane Bilayer through Lipid Intercalation into Grooves and Pockets. J Mol Biol. Aug 9;431(17):3339-3352.

Buda R, Liu Y, Yang J, Hegde S, Stevenson K, Bai F, Pilizota T. (2016) Dynamics of
Escherichia coli's passive response to a sudden decrease in external osmolarity.
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5838-E5846.

Booth IR, Miller S, Müller A, Lehtovirta-Morley L. (2015) The evolution of bacterial
mechanosensitive channels. Cell Calcium. Mar;57(3):140-50.



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