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CNSE professor contributes research to support Human Genome Project

CNSE Associate Professor of
Nanobioscience Scott Tenenbaum
Imagine knowing not only that you carry the gene for a particular disease, but also that your doctor is equipped with the ability to ensure that the condition does not develop. That type of innovative medical diagnosis, treatment and prevention could be made possible in the future, fueled in part through research being conducted by CNSE Associate Professor of Nanobioscience Scott Tenenbaum, who contributed findings to a prestigious global initiative that has just published a groundbreaking study.

On September 5, as part of the Human Genome Project, 30 papers were released, reporting on more than 1,600 experiments that have been conducted. The papers show that some type of function has been assigned to 80 percent of the genome, but also that there remains much more to explore and map.

Over the past eight years, Tenenbaum has been part of the Encyclopedia of DNA Elements, or ENCODE, consortium of more than 440 scientists from 32 laboratories around the world. A follow up to the Human Genome Project (HGP), with funding through the National Institutes of Health’s (NIH) National Human Genome Research Institute (NHGRI), ENCODE was tasked with assigning function to the more than 3 billion nucleotides comprising the human genome. In the process, they discovered that the “junk” in our DNA is not junk at all, but is actually expressed and appears to contain regulatory switches. This dark matter, originally thought to be useless, is now believed to play a major role in how genes are regulated.

“A good analogy for the human genome is a cooking recipe,” says Tenenbaum. “The five percent of the genome that represents the genes are the ‘ingredients’ and the rest, the regulatory switches of the dark matter, represent the ‘recipe.’ This is extremely important, because without the recipe for a cheese soufflé, for example, all you have are eggs, milk, flour, butter and cheese.”

As one of the only ENCODE groups that focused their research on the regulation of the RNA switches in the dark matter of the human genome, Tenenbaum and his team conducted RNA manipulation using RNA-binding proteins, which are the cellular players doing the regulation. Done at the nanoscale, this is important because, unlike DNA manipulation, using RNA as a therapeutic strategy eliminates the need to directly alter an individual’s genome.

RNA regulation has the potential to be used to correct the amount of “ingredients” that are needed to get the “recipe” right. One major implication for this research is that if scientists are able to master the regulation of RNA switches in the dark matter of the human genome, people with a gene linked to a certain disease may never develop that disease if the switches are regulated correctly.

“Nanotechnology has played an integral role in making the sequencing of the human genome possible,” says Tenenbaum. “The bulk of the current ENCODE work was done using nano-based, next-generation sequencing which allows genomic sequencing to be performed at a much higher throughput than what was done in the initial Human Genome Project.”

Tenenbaum and his team continue to discover more about regulation at the RNA level of the human genome, and their research is expanding, most recently to include work on a nanotube-based sensor technology using RNA nano-switches.

“The opportunity to break through existing scientific barriers, to enable discoveries that have the potential to benefit society, and to share my work with students and other researchers, is what drives me as a scientist,” says Tenenbaum. “The prospects of making that happen are enhanced significantly by the intellectual and technological infrastructure of CNSE.”