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Schaller

Message from the Chair

Welcome to the Department of Biochemistry in the West Virginia University School of Medicine. This is a very exciting time in the Department as we are in the midst of a period of growth. Within the last few years, three new junior faculty members have joined the Department. Our next challenge is to replace faculty members who recently retired/relocated. We plan to recruit a number of new faculty members over the next few years and are interested in candidates with expertise in biochemistry and research interests in a number of broad areas including metabolism, cancer biology, cardiovascular biology and neuroscience. These represent areas of interest of the current faculty in the department and areas of strength in the three major research centers supported by the Health Sciences Center at WVU. Our successful recruitment of new faculty is re-invigorating the research programs within the Department and has provided new opportunities for post-doctoral and graduate student training.


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WVU Biochemistry Department researcher wins $1.4 million grant

5 year federal grant will fund investigations into molecular machines that degrade proteins:

MORGANTOWN, W.Va. – The National Institutes of Health has awarded a West Virginia University researcher $1.4 million over five years to investigate how protein degradation machines work at a molecular level. David M. Smith Ph.D. a faculty member in the WVU Department of Biochemistry studies a protein degradation machine called the proteasome. The proteasome is a complex of more than 60 proteins whose major job is to degrade proteins in a high regulated and selective manner. Proteins need to be degraded for a number of reasons: they can get damaged, they get misfolded or don’t fold properly, they are no longer needed by the cell, etc. Smith explained that protein degradation often goes awry in disease. The proteasome and some of its regulators are up-regulated in many types of cancer, and interestingly, in contrast the proteasome fails to properly function in most types of neurodegenerative disease (Alzheimer’s, Huntington’s, ALS, etc..). So we are interested in understanding how the proteasome works and is regulated at the most basic level, so we can better understand it’s biological role in disease.

"The proteasome is a fantastically interesting molecular machine" Smith said. "It’s shaped a lot like a barrel, and the proteolytic sites (scissors that chop up proteins) are located on the inside of the barrel, this ensures that only proteins that are stuffed into the barrel are degraded." The decision about what proteins get degraded are primarily made by various regulatory complexes that bind to the top of the barrel. "These regulatory complexes have several important jobs", David said, "They must recognize the proper proteins and then inject them into the core for their destruction". This multistep process ensures that only the proper proteins are degraded.

Our major goal is to understand how the proteasome uses chemical energy in the form of ATP to regulate this process. One type of regulatory particle, the 19S, has a ring of 6 ATPase subunits. This ring constitutes a motor that grabs proteins, unfolds them, and injects them into the proteolytic core. We want to understand this process: "how chemical energy from ATP is coupled to physical pulling and tugging on proteins", Smith said. A further understanding of these fundamental regulatory mechanisms is essential to develop future drugs that can treat these diseases where protein degradation is misregulated.