The outer surface of cells is a factory floor of machines with varied functions: exchanging materials in and out, receiving signals, and generating energy. Studying these machines, called membrane proteins, is one of the greatest challenges of science, crucial for understanding cellular biology and developing new drugs to fight disease.
One of the largest and most comprehensive collaborations to understand the structure and dynamic function of membrane proteins was officially launched Aug. 10 with a five-year, $22.5 million grant from the National Institute of General Medical Sciences. The funding, known as a "glue grant," unites nearly 30 scientists from 14 institutions in four different countries into an effort called the Membrane Protein Structural Dynamics Consortium.
"We have been able to put together almost a dream team of people currently involved in this type of research," said Eduardo Perozo, Professor of Biochemistry and Molecular Biology at the University of Chicago Medical Center and the leader of the team. "There has been nothing like this project before."
Research on membrane proteins has traditionally been divided into two groups: structure and function. The new collaboration will focus on uniting those two areas through the study of dynamics, how a membrane protein changes shape and function over time.
To do so, the effort will unite experts across disciplines and knowledgeable in a wide range of cutting-edge technologies, including magnetic resonance and fluorescence spectroscopy, computational modeling and electrophysiology. Core facilities for different techniques will be set up at institutions for shared use by all members of the consortium - and eventually the scientific community at large.
Deeper knowledge of membrane protein dynamics will enable the development of better drugs for diseases involving defective channels and transporters, such as forms of heart disease, diabetes, and neurological and hormonal disorders. Understanding how membrane proteins allow molecules into and out of cells also can help improve drug design and delivery for an even wider range of diseases.
"We intend to start with targets for which we know the static structure at high resolutions and the function on a certain level, but don't know how they connect through dynamics," Perozo said. "Eventually, we want to develop a set of tools and reagents to be able to engineer or alter normal activity in these systems."
The Membrane Protein Structural Dynamics Consortium includes scientists at Cornell University, Columbia University, Johann Wolfgang Goethe-Universit"at (Germany), the National Institutes of Health, Stanford University, the University of California-Los Angeles, the University of Chicago, the University of Illinois, the University of Pittsburgh, the University of Toronto (Canada), the University of Virginia, the University of Wisconsin, Utrecht University (the Netherlands) and Vanderbilt University.