Contract Type: Fixed Term (4 years)
Hours: Full Time
Closing Date: 31st December 2017
Interview Date: Ongoing
iCASE Studentship with Nikon Instruments UK: Dynamic structural study of scaffolding proteins FtsZ and MipZ in Rhodobacter sphaeroides using ultra-high spatial-temporal resolution structured illumination microscopy - IRC239696
Brief description of project:
Applications are invited for a PhD studentship in the project of developing an ultra-high resolution structured illumination microscopy to study the divisome in the bacterial developing septum.
The resolution of conventional fluorescence microscopy is limited by the diffraction of light. This diffraction limit, about 200-300 nm laterally, makes the majority of subcellular structures unresolvable. Super-resolution structured illumination microscopy (SIM) doubles the resolution of conventional optical microscopy, using spatial frequency mixing to allow conventionally unresolvable sample details to pass through a conventional microscope. However, current off-the-shelve SIM systems produce less competitive, typically 120 nm, spatial resolution and moderate temporal resolution, typically at the frame rate of 0.5 Hz, limiting SIM’s capability to measure fast molecular dynamics in details.
The aim of this project is to develop a real-time macromolecular-scale-resolution SIM technique, or UltraSIM. The enhanced spatial resolution comes from the combination of pioneering synthetic optics and novel deconvolution and frequency demixing algorithms, with increased temporal resolution coming from a comprehensive optimisation of electronics, such as spatial light modulator, scientific CMOS camera and laser control system. Furthermore, the application of minimal modulated structured illumination also enhances the overall temporal resolution performance. Based on the previous proof of concept work, the UltraSIM is expected to reach 40-60 nm spatial resolution and 150-200 Hz frame rate, using generic labelling requirements and achieving high-throughput imaging capability.
The UltraSIM will be a promising method to study the divisome in the bacterial developing septum. This dynamic protein complex is the target for the development of novel antimicrobials, but the organisation and control cannot be resolved by current SIM. In the alpha-proteobacterium Rhodobacter sphaeroides SIM has been used by the Armitage group to show that two critical proteins, FtsZ and MipZ dimers each form rings, with MipZ apparently controlling FtsZ constriction, but the relationship between the proteins within the two rings is currently impossible to resolve. The MipZ dimer is unstable in vitro, making an in vivo approach the only way to really investigate the control of constriction. Using the UltraSIM, we will be able to identify the precise relationship and dynamics of the proteins within a constricting divisome.
You will be based at the Research Complex at Harwell (RCaH) situated at South Oxfordshire to deliver the proposed research. As becoming an active member in the Central Laser Facility (CLF) OCTOPUS imaging facility at Rutherford Appleton Laboratory, STFC, you will receive extensive training on the development and prototyping of advanced optical microscopy techniques, and also gain the opportunity to perceive the applications of various optical imaging methods in different biology sciences, broadening your horizons at the interface between physics and biology. You will also spend at least 6 months in the Department of Biochemistry, University of Oxford where you will learn the dynamics of the bacterial cell cycle and the effects of changing conditions etc. on the dynamics of the process. You will also learn molecular genetics, in particular methods for gene replacement with fluorescent fusions, and the controls required to test for normal expression levels and protein functionality. You will undertake a 12 week placement with the industrial partner Nikon Instruments UK. Training offered by Nikon imparts an understanding of many cutting-edge optical microscopy techniques for bio-imaging available at Nikon Imaging Centre at King’s College London, but also the theoretical background as well as practical skills in the implementation of SIM. Apart from technical training, knowledge exchange and business development training will also be provided by Nikon.
This project is supported through the Oxford Interdisciplinary Bioscience Doctoral Training Partnership (DTP) BBSRC Industrial CASE (iCASE) studentship programme. The student recruited to this project will join a cohort of students enrolled in the DTP’s interdisciplinary training programme, and will be able to take full advantage of the training and networking opportunities available through the DTP. For further details please visit www.biodtp.ox.ac.uk.
Attributes of suitable applicants:
You would be expected to possess at least an upper-second class degree (or equivalent) in bioengineering, biophysics or physiology. You will have excellent degrees in other physics, engineering and biology disciplines will also be considered.
Applicants with following skills are highly encouraged to apply: optical instrumentation, programming in Matlab or/and LabVIEW, organic/inorganic material synthesis, bacterial cell biology.
As this job does not fulfil the Home Office Code of Practice criterion for obtaining sponsored migrant worker status we will be unable to apply for sponsorship for anyone not eligible to work in the UK. At interview, all shortlisted candidates are required to bring with them identification documents and original documents that prove they hold or can obtain the right to work in the UK. You can check your eligibility here: https://www.gov.uk/check-uk-visa/y
The closing date for applications is 31st December 2017. Applications will be reviewed on an on-going basis by the Recruiting Manager and processed as soon as they are received.
We want to make our application process as easy for you as we possibly can. If you experience any problems in applying for this job, or have any feedback for us about the application process, please contact our Recruitment Hotline on 01793 867000 (8.30am – 5.00pm Monday to Friday). Please quote the appropriate IRC reference number when calling.
Prospective applicants should contact the project supervisor Dr Lin Wang (firstname.lastname@example.org) prior to submitting an application.
Applications for this project will be made via the Oxford Interdisciplinary Bioscience DTP. For further details on DTP please visit www.biodtp.ox.ac.uk.