The DSF Charitable Foundation has given a $3.9 million grant to Carnegie Mellon University's Center for Nucleic Acids Science and Technology (CNAST) to further the development of novel biomedical tools targeted at monitoring and manipulating gene expression.
The grant will allow the interdisciplinary team of researchers to advance their work aimed at providing innovative approaches for understanding and treating disease. These include the development of peptide nucleic acids (PNA), synthetic analogs of DNA and RNA that have extraordinary scientific and therapeutic potential.
"We are so grateful to the DSF Charitable Foundation for this tremendous award, which will position CNAST - and Pittsburgh - to generate fundamental biomedical discoveries in the coming decade," noted Fred Gilman, dean of the Mellon College of Science. "This award will leverage the trademark interdisciplinary work of our departments of Chemistry and Biological Sciences."
"CNAST's innovation is emblematic of the high-risk, high-return science we do, and for which federal funding is notoriously difficult to secure," added Richard D. McCullough, vice president for research and professor of chemistry. "The DSF Charitable Foundation's vision and generosity will help us to jump-start some amazing projects so that we can successfully vie for these additional funds."
Nucleic acids, which include DNA and RNA, are vital to all living systems. DNA contains instructions for making proteins, the molecules that do most of a cell's work. RNA plays a key role in turning those instructions into functional proteins. If something goes awry during this process - called gene expression- too much or too little of a protein can be made, sometimes with disastrous effects.
"At CNAST we are creating tools that will help us to answer fundamental scientific questions and lead to the development of practical applications for treating genetic and infectious diseases," said John Woolford, professor of biological sciences and co-director of CNAST.
A key aspect of CNAST's approach involves the development the synthetic nucleic acid PNA, which contains similar building blocks as strands of its natural counterparts (DNA and RNA). This feature allows the synthetic nucleic acid to bind to naturally occurring ones using the same Watson-Crick pairing rules that govern DNA and RNA binding activities which normally take place within cells. What makes PNA unique is that it has a protein-like backbone instead of a natural sugar-phosphate backbone. This synthetic backbone provides the added advantage of making the bond between a PNA and a DNA or RNA strand much more stable.
At CMU, researchers led by associate professor of chemistry Danith Ly are designing finely tailored PNAs that contain sequences complementary to target sequences of DNA and RNA found within cells. In addition, Ly's team is perfecting the ability of PNAs to enter cells. PNA's manifold attributes make it ideal for use in biomedical research. Because of its unique structure, cells fail to recognize and destroy PNAs. Moreover, because PNAs are made to bind to specific DNA or RNA targets, they can be used to indirectly monitor a pathway of gene expression. Once bound to RNA or DNA, PNA also can directly manipulate gene expression, resulting in increased or decreased production of proteins associated with diseases.
"In our labs we've been looking at PNA as a sophisticated way to regulate expression. We don't need to totally turn off a gene in order to prevent disease. If we reduce the amount of gene expression by as little as 20 percent, it could have a profound effect," said Bruce Armitage, professor of chemistry and co-director of CNAST. "This grant from the DSF Charitable Foundation will help us to take PNAs out of the test tube and put them into cells to study and potentially develop treatments for many diseases that are characterized by misregulated gene expression."
With more than 100 members spanning disciplines including biology, chemistry, physics, and chemical engineering, and with research ranging from fundamental biology to nanotechnology, CNAST is one of the largest and most diverse nucleic acids research centers in the world. In addition to supporting the center's projects, the grant from the DSF Charitable Trust will expand the center's infrastructure by creating a facility for the production of PNAs and help to educate the next generation of scientists by supporting graduate student and postdoctoral researchers.