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The Glue that Binds a Large Project

This article was originally published at the UChicago Medical Center Science Life blog (link).


The structure of the agitoxin-Shaker channel complex (from Benoit Roux’s lab webpage)

Scientific grants are usually given out one investigator at a time, funding a single laboratory’s research. But as the questions of science grow larger, and the technology needed to answer those questions grows ever more specialized and expensive, funding collaborative grants becomes increasingly common practice. One type of multi-investigator grant has been dubbed a “glue” grant, so named because it sticks together researchers from several different institutions for the common pursuit of one important science goal.

Today, the National Institute of General Medical Sciences announced a glue grant on the topic of membrane proteins, an effort that will be led from right here on the University of Chicago campus. The grant formally creates the Membrane Protein Structural Dynamics Consortium, a team of nearly 30 scientists from 14 institutions in the United States, Germany, Canada, and the Netherlands.

“We have been able to put together almost a dream team of people currently involved in this type of research,” said Eduardo Perozo, PhD, Professor of Biochemistry and Molecular Biophysics at the University of Chicago Medical Center and the leader of the team. “There has been nothing like this project before.”

Membrane proteins are the machines on the factory floor of the cell’s surface, tasked with letting materials in and out of the cell, responding to signals from other cells, and even producing energy. The family includes ion channels that Perozo (and fellow team member Benoit Roux) study, the receptors for neurotransmitters and hormones, and various other pumps, transporters, and exchangers. Figuring out how these miniature machines function will be extremely helpful in designing new drugs, both to treat diseases caused by defective membrane proteins and for improving drugs that rely upon membrane proteins to get to their target.

Traditionally, the study of membrane proteins is bifurcated into those who research their structure and those who research their function. The new glue grant-funded effort will concentrate on the connections between those two fields of study, Perozo said, uniting the best scientists to study membrane protein dynamics.

To do so, the grant will establish communal core facilities at various institutions involved in the consortium, each with their own specialty. For example, one laboratory may create a library of new antibodies useful for experiments, while another laboratory might specialize in imaging techniques such as magnetic resonance or fluorescence spectroscopy, and another offers advanced computation for complex modeling. All of the researchers involved in the effort can then utilize the facilities for their own experiments, with access eventually expanding to the scientific community at large.

“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.”

$22.5 million grant to fund international study of membrane proteins

This article was originally published at UChicago News (link).

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-University 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.

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