UW-Madison: Atlas could advance precision therapies

Aseem Ansari, (608) 265-4690, azansari@wisc.edu

Biochemists at the University of Wisconsin-Madison have created the first atlas that maps where molecular tools that can switch genes on and off will bind to the human genome. It is a development they say could enable these tools to be targeted to specific parts of an individual’s genome for use in precision medicine, developing therapies and treating disease.

The study is published this week (Monday, Nov. 7) in the Proceedings of the National Academy of Sciences. The tools are polyamides, engineered DNA-binding molecules that are an important component of artificial transcription factors. Transcription factors – both natural and artificial – determine which genes are translated into proteins inside cells.

“We know that transcription factors bind to specific sites in the genome and when they misfire they drive many diseases, including cancers,” explains lead study author Graham Erwin, a former graduate student in the lab of Aseem Ansari, a professor in the Department of Biochemistry and the Genome Center of Wisconsin. “Using insights gleaned from this research, we hope to design polyamides that can bind to these same sites and outcompete the cancer-inducing factors, helping to repress that gene.”

Transcription factors work by binding to a particular gene and then recruiting the cellular machinery necessary to read it and manufacture the desired protein, or they can stop a protein from being created.

While polyamides had already been designed to attach to particular regions of the human genome and turn corresponding genes on or off, the new study answers lingering questions about where particular polyamides bind and ultimately function in the cell.

“Our big question was, where are these molecules going across the genome?” says Erwin, who is now a postdoctoral researcher at Stanford University. “With this study, we have a whole new understanding of how they read the genome.”

READ MORE AT http://news.wisc.edu/first-cellular-atlas-of-dna-binding-molecule-could-advance-precision-therapies/