A SEED Grows in an Unexpected Direction
Cottrell Scholar 2006 Hai Lin, chemistry, University of Colorado Denver, has won a nearly $460,000 grant from the National Institutes of Health to pursue an unexpected avenue of research that grew out of his 2018 SEED Award project.
His SEED project sought to combine machine-learning techniques with unique adaptive multiscale algorithms to study channel proteins that transport protons across membranes. During his lab’s simulations of the CLC antiporter, which could be blocked by fluoride ions, they found that a closely related homolog with a similar structure, the CLCF antiporter, behaves in an unexpected and opposite way, selecting fluoride over chloride.
“I wasn’t expecting this research to lead to a major side project,” Lin said, “but that is scientific research, which is often unpredictable.”
His group formed a working hypothesis to explain the reversed anion selectivity between CLC and CLCF. Employing their results as preliminary data, they developed a NIH R15 proposal to carry out adaptive multiscale simulations to unlock the mysterious mechanisms for anion selections in these two proteins.
The CLCF is critical to the survival of many strains of oral bacteria against fluoride treatments for tooth-decay prevention. Unlocking the molecular basis of its operation could increase understanding of how these bacteria can reduce the fluoride concentration in a bacterial cell. In the long term, the knowledge gained from this research could be used to develop new therapies for oral care.
“SEED awards encourage scientists to start new risky ideas that may or may not work,” said Senior Program Director Silvia Ronco. “Hai Lin’s project is a win-win, because he conducted his plan and this plan took him to new discoveries.”
