University Times

A team of researchers from Carnegie Mellon University and Pitt has received a five-year, $13.3 million grant from the National Institutes of Health (NIH) to establish a National Technology Center for Networks and Pathways.

The center, with headquarters at Carnegie Mellon, will focus on developing fluorescent probe and imaging technologies to investigate regulatory pathways and networks in real-time in living cells. This work will generate powerful molecular biosensors for preclinical research to map the many cell-signaling networks involved in disease. Ultimately, such biosensors will be used in hospital- and office-based diagnostic medicine.

Within any given human cell, hundreds, if not thousands, of proteins may interact in precise cascades when the cell is called upon to yield a necessary product, such as a hormone, or to respond to an environmental stress, according to center faculty. Understanding the elements and dynamics of these cascades in a given cell and in real-time is the key to diagnosing why cells don’t function properly and what might be done about that dysfunction therapeutically.

“We are poised to build on an exciting, productive foundation of tools developed at Carnegie Mellon,” said Alan Waggoner, principal investigator of the grant and director of the new center. Waggoner directs Carnegie Mellon’s Molecular Biosensor and Imaging Center (MBIC), which for more than 20 years has designed fluorescent probes used worldwide for research, ranging from the study of nerve activity to understanding gene activation as part of the Human Genome Project.

The grant is one of three awarded as part of the NIH initiative, “Building Blocks, Biological Pathways and Networks Roadmap for Medical Research.” This initiative supports research that develops innovative tools that determine in real-time the amounts, locations and interactions of large numbers of individual proteins within a single cell. Such research stands to produce the next generation of research tools required to fully understand cell networks and how they function in health and disease. The NIH Roadmap is designed to transform the nation’s medical research capabilities and speed the movement of research discoveries from the bench to the bedside.

“A cell’s regulatory pathways are very complicated, and we need to learn so much more,” said Waggoner. “We’re developing a powerful toolbox of intracellular fluorescent biosensors that cells themselves will produce. With these tools, we can study in detail how all the proteins are interacting with each other in real-time in the 3-D space of a living cell.”

Effectively using these intracellular fluorescent probes and biosensors will require an array of current and new detector technologies, according to Simon Watkins, co-director of the Center for Networks and Pathways. Much of the imaging work will be carried out at Pitt’s Center for Biologic Imaging, which focuses on the application of fluorescent microscopy techniques and their translation to the study of living cells and organisms.

“The new center will truly revolutionize how we witness certain catalytic activities inside living cells,” Waggoner stated.

Integrated molecular biosensors could be sprayed onto implantable microchips to provide sensitive, accurate patient monitoring in hospital settings. Molecular biosensors also could be used in office-based diagnostic medicine, in which a biosensor could be added to a blood sample to detect instantly the presence of an infectious agent or tumor protein.

These imaging technologies will be integrated with new data analysis tools, according to Waggoner. “The center also will provide unprecedented, unique interdisciplinary training in this emerging field, as well as deliverables such as reagents and methodologies which can be used worldwide,” he said.