A BBSRC PhD studentship is available in Correlative cryo- single molecule fluorescence and electron microscopy of bacteria.

Project Description

Applications are invited to join the University of Nottingham BBSRC iCASE Studentship to undertake an innovative four-year PhD training programme. 

We will use a new and innovative combination of Cryo- correlative light and electron microscopy (cryo-CLEM) to image the SilABC copper/silver effluxer, which spans both the inner and outer membranes in E.coli cells. This is an important antimicrobial target and we wish to understand its function in vivo as part of a wider investigation of the bacterial silver/copper resistance mechanism with ever increasing clinical importance. We wish to observe the structure and dynamics of this complex in its native cellular environment, and investigate not only its function but also how this function maybe inhibited. To do this we will apply new, unique and cutting edge methods combining both structural and spectroscopic methods. 

The project will be located within the Central Laser Facility (CLF) at the Research Complex at Harwell, where cutting-edge super-resolution cryo-CLEM imaging techniques are being actively developed. Super-resolution microscopy bypasses classic diffraction limit barrier in optical imaging. As a fluorescence microscopy method, it takes the leading role to study the distribution and organisation of specific biomolecules in cells. Cryo-electron microscopy (cryo-EM) is a powerful tool to obtain up to sub-nanometre resolution molecular and cellular ultrastructure. Both techniques were recognised by the Nobel Prize in Chemistry recently (2014 and 2017). Super-resolution cryo-CLEM combines both of these techniques to link function to structure in complex biological systems, offering macromolecular level resolution in both imaging modalities. Apart from conventional cryo-CLEM approach, a proprietary lens technology has been developed which enhances the resolution performance of conventional cryo-FM by a factor of 3. Furthermore, the resolution can be improved to a few tens of nanometers applying single molecule localisation imaging. This system is mounted within a Focused Ion Beam (FIB)-Scanning Electron Microscopy system which provides complementary high resolution information. As such we will hope to attain resolutions of a few nanometers for localisation of optical signals within the EM data. This is an innovative and potentially data-rich technique with very high impact that will link the functional and structural information in cells preserved in a near-native state. 

This project will be based at the Research Complex at Harwell (RCaH) in Oxfordshire and will be supervised by Dr. David Scott (School of Biosciences, University of Nottingham/RCaH) and Dr. Lin Wang (Central Laser Facility). There will be a three-month industrial placement at Laser Support Services (Oxfordshire, UK) as a compulsory part of this project. 

Applications are invited from students who have/expect to graduate with a first/upper-second UK honours degree, or equivalent qualifications gained outside the UK. Students with an appropriate Masters degree are particularly encouraged to apply. This is a multidisciplinary project so we seek candidates with backgrounds from either the physical or biological sciences. Applicants with prior experience in imaging instrumentation, image analysis, or programming in Matlab or/and LabVIEW, are encouraged to apply. However, experience in these areas is not essential as training will be provided. 

How to apply

Applicants should go to https://www.nottingham.ac.uk/bbdtp/icase-studentships/icase-studentships.aspx to download the specific application and reference forms. 

Applications should include: a fully completed application form; a CV of no more than two A4 pages; a transcript of module marks achieved at the time of submission; and two references. Application forms and CVs should be named in the following format: SURNAME-initial-DTP_BBSRC_iCASE-application.doc (.docx or .pdf) and SURNAME-initial-BBSRC_iCASE-cv.doc (.docx or.pdf) e.g. SMITH-A-BBSRC_iCASE-application.doc 

Applications should be sent via email with the subject line ‘BBSRC iCASE Studentship’ to ([log in to unmask]@stfc.ac.uk) by the deadline: noon, 26th April 2018. 

References should be sent directly from the referees to ([log in to unmask]@stfc.ac.uk) by the deadline: noon, 26th April 2018. Please note it is the applicant’s responsibility to ensure that the references are sent in good time for the deadline. Further details are on the reference form. 

Enquiries should be sent to: ([log in to unmask]@stfc.ac.uk) 

Please quote ref: BBSRC iCASE

Funding Notes
Funding is available for four years from October 2018. A full award would be fees plus an annual stipend. This is set by the Research Councils and is £14,777 for 2018/19. 

Eligibility for full funding is restricted to UK and EU students.