August 27, 2019
Liskin Swint-Kruse featured in Biochemistry and Molecular Biophysics Seminar on Aug. 28
Submitted by Biochemistry and Molecular Biophysics
Liskin Swint-Kruse, professor of biochemistry and molecular biology at University of Kansas Medical Center, is the featured speaker for Biochemistry and Molecular Biophysics Seminar on Wednesday, Aug. 28. She will present "Rheostats and Toggle Switches for Modulating Protein Function" at 4 p.m. in 120 Ackert Hall.
Swint-Kruse earned her doctorate in biochemistry from the University of Iowa in 1995 under the direction of Andy Robertson. She performed multidisciplinary postdoctoral work in the W. M. Keck Center for Computational Biology under Kathy Matthews, Rice University; and Monte Pettitt, the University of Houston. After serving as a research scientist at Rice University, in 2004 she moved to the University of Kansas Medical Center as an assistant professor in the department of biochemistry and molecular biology, where she is now a professor and chair. Her lab studies the evolution of protein functional variation, which has applications to personalized medicine and protein engineering and is funded by the W. M. Keck Foundation and NIH. She has additional research interests in transcriptional control of bacterial metabolism.
Presentation: Personalized medicine is hindered by our limited ability to predict the functional outcomes of amino acid changes. To that end, many computer algorithms have been written to analyze the amino acid sequences of protein families. These are based on the rationale that "Changes that arise during the evolution of functional variation can be used to predict mutational outcomes." With these methods, catastrophic mutations at conserved positions can be readily identified. However, predictably identifying substitution outcomes at nonconserved positions remains a challenge. We have considered the underlying assumptions that are shared by many computational algorithms. From comparison with experiment, we found that the assumptions do not apply for a certain group of nonconserved amino acids; we estimate these positions can comprise >25% of a protein's sequence. Additional complexities include: (i) the effects of defining the computational and biological thresholds that define "important" amino acids; (ii) the co-occurrence of many different patterns of amino acid change in evolutionary data; (iii) the "rheostatic" mutational outcomes that occur at some nonconserved sites; (iv) epistasis (non-additivity) among multiple mutations; and (v) the fact that a large fraction of a protein’s amino acid contribute to overall function. These areas provide direction for future experimental studies.