B.S., Biochemistry, Mississippi State University, 1991; Ph.D. (Med. Dr.), Biophysics and Structural Biology, Karolinska Institute, 1999
Eukaryotic membrane proteins comprise approximately 60% of all drug targets and are consequently immensely important for biomedical research. Despite their importance, only few could thus far be studied at the structural level. My research focuses on the crystallization, structure and function of eukaryotic membrane proteins.
Electron crystallography is the main tool employed to study these proteins in my laboratory. The approach of 2D crystallization and electron crystallography is particularly suitable for highly fragile membrane proteins such as many eukaryotic ones. Initially, this involves testing of conditions for growing two-dimensional (2D) crystals, usually by reconstituting the detergent-solubilized membrane protein into a phospholipid bilayer. Once crystallization parameters have been identified by electron microscopy of negatively stained samples, electron cryo-microscopy (cryo-EM) is employed to collect high-resolution data. The structure is then obtained by image processing.
Although electron crystallographic methods are well developed, little is known about the factors important in 2D crystallization, and screening protocols as for 3D crystallization do not exist. An important sideline of my research interests aims at developing screening methods and strategies for 2D crystallization and understanding the underlying mechanisms. Further directions of methods development are geared towards cryo-EM data collection and analysis.