Engineering Regulated Biological Adhesion

Wendy E. Thomas, Ph.D.
Associate Professor, Department of Bioengineering Co-Director, Biological Physics, Structure and Design (BPSD) Program University of Washington
Thursday, January 30, 2014 - 4:30pm

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Abstract

Engineered biological adhesive molecules are critical to many areas of bioengineering, include diagnostic devices, molecular imaging, and drug delivery. Cell adhesion, which is mediated by naturally occurring adhesive molecules, and is critical to many other fields, such as tissue engineering, thrombosis, and microbiology. The Thomas lab studies the regulation of biological adhesive molecules, with particular emphasis on mechanical and allosteric regulation, and applies this knowledge to engineer novel adhesives and methods of inhibiting or regulating cell adhesion. A major focus of the Thomas lab is the study of catch bonds, which are receptor-ligand interactions that are strengthened by tensile mechanical force. The bacterial adhesin FimH provides a model system for understanding the molecular biophysics of catch bonds and the role of catch bonds in cell biology. The Thomas lab uses an interdisciplinary approach that includes genetic engineering, single molecule force spectroscopy, atomistic structural analysis and simulations and mathematical modeling. This work has enabled us to understand how catch bond behavior is caused by force-regulated allosteric conformational changes. The Thomas lab also studies how catch bonds contribute to bacterial adhesion in flow. Specifically we have determined how catch bonds, together with the fimbrial organelles on which they are expressed, allow bacteria to have mobility when conditions are safe, but to lock on when wrenched by high flow. This function is reminiscent of a nanoscale locking seatbelt, and has inspired several novel adhesive technologies.

Biography

Wendy Thomas earned a BA degree in Molecular Biology at Princeton University in 1987, and then worked as a research technician for 10 years at Howard Hughes Medical Institute studying lipid biochemistry. She then earned a master’s degree in Applied Math and a Ph. D. in Bioengineering at the University of Washington in 2003. In 2004, she accepted a tenure track faculty position in Bioengineering at the University of Washington, where she is now an Associate Professor. Wendy has applied her interests in molecular biology, math, and bioengineering to combine experimental and computational approaches to study biological adhesion and to design new biotechnologies based on her discoveries. In addition to her research interests, Wendy is also interested in teaching and mentoring students. Her courses have been among the highest rated courses in her College, and she now co-directs the Biological Physics, Structure and Design (BPSD) graduate program, and is Assistant Chair for Academic Affairs in Bioengineering.

Related Articles:

 

http://www.pnas.org/content/early/2013/11/01/1314395110.full.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905812/