Dr. Michael G. Malkowski, Hauptman-Woodward senior research scientist, has received a $6.7 million grant from the National Institutes of Health in support of his work to establish the Membrane Protein Structural Biology Consortium as one of nine centers in the United States responsible for determining membrane protein structures within a larger NIH biology-based initiative.
Why is this important?
The grant entitled Multi-Level Optimization of Membrane Proteins was awarded as part of the NIH National Institute of General Medical Sciences Protein Structure Initiative. The PSI now begins its third five-year phase, PSI:Biology. The funds establish the Membrane Protein Structural Biology Consortium (mpsbc.org) as one of nine centers in the nation which are responsible for determining membrane protein structures within the initiative.
Each cell in the human body is surrounded by a kind of ultra-thin skin called a cell membrane, which isolates the inside of the cell from its surroundings. This membrane is punctuated by protein molecules, some of which mediate the passage of important molecules - such as nutrients or wastes - into and out of the cell, and others of which transmit signals of various kinds. Membrane proteins are key to many life processes.
The MPSBC combines the diverse expertise of three investigators: Malkowski, Dr. Mark Dumont, associate professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry in Rochester, New York, and Dr. Michael Wiener, associate professor in the Department of Molecular Physiology and Biological Physics at the University of Virginia in Charlottesville, Virginia.
Malkowski, who in addition to his HWI post is also an assistant professor at the University at Buffalo, said: "I am pleased and excited to be working with my colleagues in Rochester and Virginia to tackle the technical challenges associated with determining the structures of membrane proteins. We have assembled a strong team. Each of us brings unique experiences and expertise to the problem that together, will provide us with a strong knowledgebase to meet these challenges head on."
What will the Center do?
The Center will focus on central problems associated with membrane protein structural biology, with the emphasis on overcoming the technical barriers, using improved technologies to solve structures, and disseminating these improvements to the biological and structural biological communities. The involvement of the three different laboratories also brings together a range of pre-existing facilities and personnel, ongoing structural projects, ties to collaborators working on important targets, and existing infrastructures for interacting with the broader scientific community.
Membrane proteins play critical roles in the physiology of humans and other organisms. However, little is known about their three-dimensional molecular structures. This project is designed both to solve structures of medically important membrane proteins and to improve the available technologies for solving such structures. Knowledge of protein structure is crucial for understanding the functions of proteins and designing drugs that modify their functions.
Malkowski's research is focused on solving those structures and improving the technologies to lead to an understanding of why and how these biological processes in the human body happen - knowledge which is critical to the long-term future development of new or combined therapeutic approaches for the treatment of a wide range of diseases with fewer unwanted side effects.
His research has the potential to have medical relevance for literally millions of people worldwide.
"There are very few membrane proteins that have been characterized in molecular detail. These proteins carry out many significant biological processes in our body," Malkowski said. "As roughly 60 percent of the drugs prescribed today for different aliments target membrane proteins, any additional structural knowledge we can contribute has the potential to be targeted for the design of new and improved drugs."
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