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Center on Proteolytic Pathways
In 2004 the National Institutes of Health (NIH) selected a team led by Jeffrey Smith, Ph.D., to establish the Center on Proteolytic Pathways (CPP). As part of the NIH Roadmap for Medical Research, the center develops technology to study the behavior of proteins and to disburse that knowledge to the scientific community at large.
Proteases are a class of enzymes that regulate much of what happens in the human body, both inside the cell and out, by cleaving peptide bonds in proteins. Through this activity, they govern the four essential cell functions—differentiation, motility, division and death—and activate important extracelluar episodes, such as the cascading effect in blood clotting. Simply stated, life could not exist without them.
Proteolytic pathways, or proteolysis, are the series of events controlled by proteases that occur in response to specific stimuli. In addition to the clotting of blood, the production of insulin can be viewed as a proteolytic pathway, as the activation, regulation and inhibition of that protein is the result of proteases reacting to changing glucose levels and triggering other proteases downstream.
The Need and Opportunity for the Center on Proteolytic Pathways
Proteolytic pathways are key to the pathology of virtually every type of human disease, including, but not limited to, viral infections, inflammation, thrombosis, cancer, Alzheimer’s and emphysema. Any advance in this field that increases understanding of proteolysis and presents opportunities to regulate it could potentially provide health benefits so far-reaching that we cannot fully imagine their impact.
Although the completion of the Human Genome Project identified the majority of human proteases, major and fundamental gaps exist that prevent meaningful scientific research. We do not know the focus of most of these proteases. We do not know how each protease recognizes its target substrate (the protein that it will cleave and activate), nor is it clear how these important enzymes link to other cellular pathways.
The Center on Proteolytic Pathways aims to fill these holes by developing technology to study these problems and distributing it to other scientists; we will be a national resource, disseminating much of the information through the Proteolytic Map (PMAP). It is our hope that by providing investigative tools to other researchers, the proteolytic knowledge base will grow rapidly, and can be translated into therapeutic benefit for disease.
The Research Team
The scientists participating in the CPP represent some of the world leaders in chemical biology, computational biology and biological imaging. Through their experience, guidance, insight, scientific curiosity and passion for this program, the CPP will move forward quickly and effectively, meeting its goal to make proteolysis a known by the year 2020.
