Christopher W. Akey, Ph.D.
Professor of Pharmacology, Physiology & Biophysics
We are studying the structure and function of macromolecular machines involved in cellular processes that include protein translocation across cell membranes mediated by the Nuclear Pore Complex (NPC), ribosome-channel complexes, and the Type IVb secretion system of Legionella pneumophila. We also study apoptosomes that function in the intrinsic path of programmed cell death and the Nucleoplasmin family of histone chaperones. In our work, we use biochemistry and molecular biology, coupled with high resolution cryogenic electron microscopy, X-ray crystallography and molecular modeling to create snapshots of these nano-machines. In addition, the recent ground breaking prediction of protein structures with deep learning algorithms (cf. Alphafold2 and Rosettafold) is now able (in many cases) to provide “homology” models that can be used to improve the structure of supramolecular complexes when combined with flexible fitting. This approach provides medium and high resolution models that allow us to infer the functions of these large machines in their respective cellular pathways.