In his recent address to the Senate Appropriations Committee, NIH Director Francis Collins made cryo-EM of membrane proteins, like ABCA1, a national funding priority and he highlighted my group’s plans and efforts toward this exceptional scientific opportunity. Dr. Aller is a world-renowned expert in the structural biology of molecular pumps that reside at the surface of cells in the membrane that forms the protective boundary for the cell. During his research efforts at the University of Alabama at Birmingham (UAB), he has been working to understand the atomic structure of these proteins, their molecular dynamics, and the mechanisms by which novel drugs can interact and influence their function. He has extensive training and experience studying membrane proteins, including NRSA post-doctoral training in x-ray crystallography in which he solved the first structure of any mammalian ATP-Binding Cassette (ABC) transporter, called P-glycoprotein (Pgp), and published in Science. Pgp is perhaps the most dominant drug pump involved in classical multidrug resistance. In independent work at UAB, his group refined the Pgp model using new x-ray data to produce more accurate structure that revealed new amino acid residues involved in drug-binding. He showed these first structures represent high-affinity drug-binding conformations. His group has also published the first atomic model of Pgp in the low-affinity outward-facing conformation to better understand the complete catalytic cycle of the transporter and low-affinity drug interactions. His group also builds new computational tools for training students in cutting-edge structural biology and they have published more than 25 manuscripts. Dr. Aller was awarded a prestigious NIH Director's New Innovator Award to accelerate the high-resolution crystal structure determination of human membrane proteins. Dr. Aller now turns his attention to the study of ABCA4 structure and function by forging an exciting new direction using cryo-EM to achieve the first-ever high-resolution structure of ABCA4. Dr. Aller will also adapt a drug screening assay used for Cystic Fibrosis to find new drugs for treating ABCA1-mediated disease in vision.
University of Alabama at Birmingham