Scientists at Weill Cornell Medicine have unveiled a groundbreaking tool named SCOPE, which significantly enhances the ability to identify and study proteins that regulate gene activity in living cells. This innovative technology, developed through collaborative research led by Dr. Shuibing Chen and Dr. Peter Schultz, promises to advance the understanding of gene regulation mechanisms crucial for various biological processes and diseases.
SCOPE technology is based on the use of a highly unusual amino acid, AbK. It remains dormant within mammalian and bacterial cells, but is activated upon exposure to ultraviolet (UV) light. By taking advantage of this unique property SCOPE is able to efficiently isolate proteins that are binding to regulatory DNA regions that control gene expression. This groundbreaking new capability allows researchers to examine proteins’ interactions with DNA. Not only that, they are able to watch how these interactions impact gene activity in real-time.
Development and Leadership of SCOPE
Shuibing Chen, MD, is Kilts Family Professor of Surgery and Director of the Center for Genomic Health at Weill Cornell Medicine. He was joined in co-leading this research by Dr. Peter Schultz, Skaggs Presidential Chair of Chemistry and CEO of Scripps Research. Together, their collaboration has produced a powerful new tool that goes far beyond any effort to study protein-DNA interactions that have come before.
Dr. Chen was hopeful about SCOPE’s broader applications in science research to come. He stated, “We expect this to be useful as a very general laboratory tool, and we already plan to use it for research on specific disorders, including type 1 diabetes.” SCOPE can make a real difference in improving the conduct of basic research. In fact, it’s arguably one of the most important pieces in helping us gain insight into multifactorial disease.
Dr. Jiajun Zhu, an essential member of the research team, underscored the advantages of employing AbK. He described how it all linked to the SCOPE framework. He noted, “This reduces the chances of unwanted interactions between the SCOPE tool and other proteins, which effectively gives SCOPE a high sensitivity, enabling it to detect proteins that are DNA-bound only weakly and/or transiently.” This high sensitivity would allow for the discovery of major breakthroughs to come in the field of gene regulation.
Applications in Stem Cell Research
In real-world applications, SCOPE has already been used to research stem cells. In doing so, the researchers have precisely pinpointed three proteins that are key players in regulating gene activity in these cells. Two of these proteins are key players in maintaining stem cells in their pre-differentiated, stem cell-like state. In parallel, the third protein promotes these cells to differentiate into more specialized, adult cell types.
The implications of these findings are profound, as understanding how these proteins function may unlock new strategies for regenerative medicine and tissue engineering. By manipulating these proteins, scientists could potentially guide stem cells to develop into specific cell types needed for therapeutic purposes.
Future Directions and Broader Implications
Back in Charlotte, Dr. Chen and Dr. Zhu have plenty of ambitious plans ahead. In addition to stem cells, they now aim to use SCOPE in other cell types to identify gene-regulating proteins in cardiomyocytes, insulin-producing pancreatic cells, neurons and others. It is this deeper thinking that can lead to breakthrough improvements. It’s advancing our understanding of conditions such as cardiac arrhythmias, type 1 diabetes and degenerative brain diseases.
Using SCOPE, researchers can unravel complicated gene regulatory processes with exceptional detail. We expect this new capability to power transformational research, revealing new ways diseases develop and identifying new paths to therapeutic targets. The researchers are confident this new tool will transform laboratory studies. They want it to lead to breakthroughs that can be translated into the clinic.