Immunophysics of CTLA-4: an advanced microscopy study

David Sansom (primary)
Institute of Immunity and Transplantation
UCL
Philip Jones (secondary)
Department of Physics & Astronomy
UCL

Abstract

Immunophysics is the application of biophysical tools to better understand the molecular mechanisms of immunological processes. In this project we will develop a novel advanced light microscopy system that combines optical tweezers and fast fluorescence imaging to study the trafficking and binding affinities of CTLA-4, a protein that is crucial in (negative) regulation of the immune response. The quantitative data that will be obtained by this project will enable a comprehensive understanding of CTLA-4 trafficking, internalization, recovery and recycling that is crucial for future therapies with CTLA-4 targeting drugs.


References

1. P. H. Jones, O. M. Maragò & G. Volpe. ‘Optical tweezers: principles and applications’, Cambridge University Press, 561pp (2015).
2. P. Polimeno et al. ‘Optical tweezers and their applications’, Journal of Quantitative Spectroscopy and Radiative Transfer 218 131-150 (2018)
3. B. Rowshanravan, N. Halliday & D. M. Sansom. ‘CTLA-4: a moving target in immunotherapy’, Blood 131 58-67 (2018)
4. S. Khailaie, B. Rowshanravan, P. A. Robert, E. Waters, N. Halliday, J. D. Badillo Herrera, L. S. K. Walker, D. M. Sansom, M. Meyer-Hermann. ‘Characterization of CTLA-4 trafficking and implications for its function’, Biophysical Journal 115 1330-1343 (2018)
5. O. S. Qureshi, Y. Zheng, K. Nakamura, K. Attridge, C. Manzotti, E. M. Schmidt, J. Baker, L. E. Jeffery, S. Kaur, Z. Briggs, T. Z. Hou, C. E. Futter, G. Anderson, L. S.K. Walker, D. M. Sansom. ‘Trans-endocytosis of CD80 and CD86: A molecular basis for the cell extrinsic function of CTLA-4’, Science 332 600-603 (2011) (WoS Highly cited)


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyImmunology
Techniques & Approaches
BiophysicsImage ProcessingMicroscopy / ElectrophysiologyMolecular Biology