Link: University of Iowa

Dr. Miles Pufall receives NSF CAREER Award

_D3A8298Dr. Miles Pufall was recently awarded the NSF’s most prestigious grant, a CAREER award entitled “Allosteric regulation of transcription factor DNA binding specificity, kinetics, and cellular activity.”

Over the past several years, large-scale in vitro DNA binding experiments have extended our understanding how transcription factors select their genomic targets to regulate the proper genes. Despite this progress, our ability to predict where a transcription factor will bind in the genome, and to predict its activity once it gets there is still poor. One issue is that none of the current models account for how how cellular signals, including small molecular ligands and chemical modifications, change the sequence preference and kinetics of transcription factor DNA-binding.

Under this 5-year grant, Dr. Pufall will be using the glucocorticoid receptor as a model transcription factor to understand how small molecule ligands, synthesized by the Advanced Organic Synthesis Laboratory course at Butler University, and phosphorylation change sequence specific DNA binding in vitro and in cells. In collaboration with the lab of Dr. Maria Spies, Dr. Pufall will also explore how these cellular signals change the in vitro kinetics and stoichiometry of DNA binding using advanced single molecule techniques. How these kinetic profiles impact cellular behavior will be explored using Single Molecule Tracking in collaboration with the lab of Dr. Gordon Hager at the NIH. These studies will provide a vastly more realistic picture of how transcription factors make the critical decision of where to bind DNA and regulate genes in the complex environment of the cell.

Leave a Reply

You must be logged in to post a comment.