The primary interest of our lab is to understand the mechanisms that cells have developed to move ions and small molecules across cell membranes. This work has also led us to investigate the mechanisms whereby mutations in certain transporters or ion channels lead to specific pathological conditions. P-type ATPases are primary active transport proteins that are responsible for establishing many of the ion gradients that exist across both eukaryotic and prokaryotic cell membranes. A major theme in our lab for many years has been the investigation of the structure and mechanism of the Na,K-ATPase, the Ca-ATPase from sarcoplasmic reticulum, and the H,K-ATPase of gastric mucosa. In another line of investigation, we are studying the mechanisms of serotonin and GABA transport by neuronal serotonin and GABA transporters. These transporters are members of a class of proteins that couple neurotransmitter uptake to the transport of sodium ions and often to other ions as well. These transporters are targets of both clinically useful drugs such as SSRIs used to treat depression and also drugs of abuse such as cocaine and methamphetamine. The serotonin transporter, in particular, exhibits characteristics of both an alternating access transporter and an ion channel, and we are interested to know how this observation can be explained. Over the past three or four years our lab has also begun to investigate the mechanisms of selective ion permeation through ion channels of both bacterial and animal cell membranes. Loss of ion selectivity is sometimes linked to mutations in the genes for ion channels that cause different forms of pathology.
Our work on the structure and mechanism of each of these transporters and channels has historically used techniques of membrane protein biochemistry, multiple types of spectroscopy, electrophysiology, and molecular biology. As more atomic level structures of transport proteins have become available over the past 10-15 years, we have moved primarily to using molecular dynamics simulations of these transporters as a tool to elucidate dynamic mechanistic details. These details are not usually captured by static protein structures and are often inaccessible to direct experimental measurement.
October 1, 2015
Our paper on ion permeation in Nav channels was accepted today at PLOS Comp. Biol.
August 18, 2015
We extend a hearty welcome to Sarah Holzmann (Lehigh University) who has joined the lab as a new graduate student.
Dr. Farley discussed our ongoing work on ion-selective K channels and neurotransmitter transporters in two seminars at the Centre for Molecular Simulation at the University of Calgary.
May 19, 2015
We are happy to welcome Yi Shi (University of Buffalo) to the lab as a new graduate student.