Title of Research Group: Membrane Structural and Functional Biology

Principal Investigator: Professor Martin Caffrey

Institution: Trinity College Dublin

School: School of Biochemistry and Immunology

macromolecular X-ray crystallography, membrane lipids and proteins, membrane mimetics, robotics, structure-function relationships

A healthy cell, and by extension a healthy organism, requires intact, selectively permeable membranes. Whist lipids are essential to membrane form and function, membrane proteins can be viewed as vital, nanometer-sized molecular robots that serve critical signal transducing, enzymatic, structural, and transport roles. As targets of disease causative and treatment agents the health consequences of membrane protein malfunction are obvious. Our approach to understanding how these proteinaceous nano-robots perform at a molecular level relies on obtaining a high-resolution structure for each using macromolecular X-ray crystallography. In the Membrane Structural and Functional Biology Group, a multifaceted approach is taken to produce structure-grade crystals for crystallographic purposes. Emphasis is placed on crystallization in lipid mesophases by what is referred to as the in meso method. The molecular mechanism of crystal nucleation and growth is also being studied with a view to more rational and productive crystallogenesis. Success in obtaining crystals, and ultimately the atomic structure of membrane proteins will enhance our understanding of and control over some of the most fundamental processes underlying cellular function that are integral to human health. To this end the group extensively uses Synchrotron Radiation and now also Free Electron Laser facilities for crystallography.

Techniques: Protein Crystallography (PX), Macromolecular Crystallography (MX)

Facilities: Diamond, APS, SLS, LCLS and CHESS


Group (as of 2014): 4 Ph.D. and 4 PDRA

Participating group members at SR/FEL/neutron facilities (period 2008-2014): 3 Ph.D and 3 PDRA

Impact: Access to FEL facilities provides new methods for complex crystallographic determinations instantaneously which are otherwise not solvable by SR techniques.

Publication Highlights:

  1. “Fast native-SAD phasing for routine macromolecular structure determination”, Weinert T., Olieric V., Waltersperger S., Panepucci E., Chen L., Zhang H., Zhou D., Rose J., Ebihara A., Kuramitsu S., Li D., Howe N., Schnapp G., Pautsch A., Bargsten K., Prota A.E., Surana P., Kottur J., Nair D.T., Basilico F., Cecatiello V., Pasqualato S., Boland A., Weichenrieder O., Wang B-C, Steinmetz M.O., Caffrey M. & Wang M.,
    Nat Methods (2014) doi:10.1038/nmeth.3211
  2. “‘Hit and run’ serial femtosecond crystallography of a membrane kinase in the lipid cubic phase”, Caffrey, M., Li, D., Howe, N., Syed S.T.A.,
    Phil. Trans. R. Soc. B. 369 20130621

Website: https://www.tcd.ie/Biochemistry/research/m_caffrey.php