"Our unique contribution is the use of atomistic simulation to design the surface and optimize the conditions to enhance hybridization efficiency in order to increase the detection resolution," said Wei. "The research will facilitate the development of new biodevices based on nucleic acid hybridization."
The team presented their work at the 2016 Annual Meeting of the American Institute of Chemical Engineers and are working to design and test experimental sensors capable of detecting nucleic acid biomarkers.
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SENSORS THAT ENTER NUCLEI AND REPORT ON DNA REPAIR
Henry Herce, a research scientist at Rensselaer Polytechnic Institute (currently at Dana-Farber Cancer Institute) takes yet another tact to solve the problem of cancer detection in living cells. His research focuses on developing molecules that can enter the nucleus of a cell and bind to a specific protein there known as the Proliferating Cell Nuclear Antigen (PCNA).
PCNA, nicknamed the "ring master of the genome," is one of the key proteins in DNA replication and repair. DNA replication is essential for the survival, growth and spread of cancer, making it an intriguing target for tumor labeling and inhibition.
In a series of publications in the Journal of the American Chemical Society (2014) and Nucleus (2014) enabled by Stampede, Herce and his collaborators described the creation of a novel peptide - a chain of several amino acids -- that can enter the cells of an organism, separate from its carrier molecule and bind to PCNA. They also uncovered the nature of the interactions between the peptides and their PCNA targets in atomistic detail.
Finally, they showed that both replication and repair sites can be directly labeled in live cells -- the first cell-permeable peptide marker for these two fundamental processes -- and introduced a PCNA staining method that causes the target molecule to light up so they can assess its distribution.
The simulations complemented experimental results and offered insights into how chemical modifications to the peptide's design can enhance its efficiency, increase its stability, and allow for intracellular delivery.
"The discovery represents a versatile tool for instantaneously labeling repair and replication processes in fixed and live cells," Herce said. "Down the road, it could lead to a new tool for early cancer detection."
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