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Professor Martin Caffrey

Membrane Structural and Functional Biology


Professor Martin Caffrey
Phone: +353-1-8964253
Fax: +353-1-8964257
Email: martin.caffrey@tcd.ie
Location: Room 5.62, Trinity Biomedical Sciences Institute


RESEARCH INTERESTS

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. This is proving to be a generally useful approach for membrane protein structure determination. Because crystallization takes place in a membrane environment, the in meso method is likely to be favored by the target membrane protein. We have built state-of-the-art robots that perform in meso crystallization in high-throughput fashion and that require miniscule amounts of protein and lipid. They are used to generate 3-dimensional crystals for high-resolution structure determination of a select group of membrane proteins and their complexes. The target group covers a broad range of membrane protein types including eukaryote and prokaryote, integral and peripheral, monomeric and multimeric proteins, as well as protein-protein, protein-peptide and protein-ligand complexes. The bulk of the target proteins are produced in-house; others are provided by collaborators.
 
In parallel with on-going crystal structure determination projects, considerable effort is devoted to improving crystallogenesis and to broadening the range of membrane protein targets that yield to structure determination. This is done by implementing a synthesis program whereby lipids with desirable physico-chemical characteristics are produced for use in in meso crystallization trials. 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.

Useful Information

RESEARCH PERSONNEL

Bailey J
Boland, C 
Caffrey, M 
Howe, N 
Huang, C-Y 
Leng, S
Ma, P
Tutty, M
Vogeley, L 

FUNDING

Framework Programme 7
National Institutes of Health USA
Science Foundation Ireland

PUBLICATIONS

Publications


Last updated 18 December 2014 bbutler@tcd.ie (Email).