Keywords: Superresolution microscopy, live-cell single molecule imaging, cell sensing and remodelling dynamics, T cell Biology, Immunophysics and Immunoengineering
Immune responses mediated by lymphocyte T cells involve the interaction between the T cell receptor (TCR) and peptides carried by antigen-presenting cells. It has been postulated that several transmembrane protein complexes and lipidated proteins co-ordinately act to serve as a focal point for TCR-mediated T cell activation. There is a lack of information on the dynamic aspects of this activation processes, as well as the precise molecular interactions and number of proteins required to trigger the process. Another important piece of information that would benefit from further investigations is the role that the physical and chemical properties of the plasma membrane and its lipid constituents play in a concerted manner with the proteins. The lack of viable experimental methods for studying membrane dynamics and oligomeric states in living cells at close-to-resting state has profoundly limited our understanding of the resting and early stages of immune cell activation and synapse formation. To overcome this limitation, we propose to (i) employ software-based methods to achieve superresolution microscopy (obtaining similar resolution as in Structured Illumination Microscopy), (ii) develop novel methods to fully control, engineer and manipulate the activation and synapse molecular events at the single cell level. To this end, the candidate will employ both chemical and physical advanced approaches, such as chemical hydrogels and/or either optical trapping or acoustic trapping. (iii) And integrate imaging correlation analysis methods to unravel the spatio-temporal characteristics of the molecular interactions, dynamics and oligomeric states during T cell activation and synapse formation. These approaches will be integrated with a laser-free microscope developed at the Oxford University spin-out local company Aurox Ltd. It is envisaged that this technology platform may contribute to widening existing knowledge of immune cell signalling, and its usage could be widened to include other cell types and inter-cellular interactions.
This project will be carried out mainly at the Research Complex at Harwell, where Dr. Bernardino de la Serna is a Principal Scientist, and involves a close communication between the associated partners: Prof. Martin Booth, an expert in optics and biophotonics manipulations. Dr. Jorge Bernardino de la Serna, an expert in advanced quantitative molecular localisation and dynamics imaging (both diffraction-limited and in superresolution modes), and its applications to the understanding of lipid-protein interactions in living cells during T cell manipulation; Aurox Ltd, a local (Oxfordshire) company founded by University of Oxford academics (including Prof Booth) developing a novel technology based on laser-free microscopy, where the candidate is expected to undertake a placement minimum of 12 weeks over the 4 year-funded project.
Attributes of suitable applicants:
This project is suited for highly motivated and enthusiastic students with a strong interest in fluorescence superresolution imaging and cell biology (molecular/cellular dynamics). Candidates should hold a Masters Degree in Physics, Biophysics, Biochemistry or related field. Applicants should have excellent analytical skills, and innovative and cross-disciplinary thinking. Previous experience in advanced fluorescence imaging, live-cell microscopy and quantitative image analysis will be beneficial but not essential. Training in cell and molecular biology is also beneficial but not essentially required. Knowledge in coding (such as Python, MATLAB, Java) will be appreciated.
How to apply:
If you are interested in applying for a BBSRC iCASE studentship please contact the named supervisor, Jorge Bernadino de la Serna ([email protected]
) for further information and to determine whether they would encourage you to apply. Applicants who wish to apply for a BBSRC iCASE studentship should apply directly to the Interdisciplinary Bioscience DTP via [email protected]
essentially required. Knowledge in coding (such as Phyton, MATLAB, Java) will be appreciated.
This project is funded for four years by the Biotechnology and Biological Sciences Research Council BBSRC. BBSRC eligibility criteria apply (View Website Annexe 1). EU nationals who do not meet BBSRC residence criteria are encouraged to contact the programme administrator to check their eligibility for BBSRC funding before submitting a formal application. Successful students will receive a stipend of no less than the standard RCUK stipend rate, currently set at £14,777 per year.