CAREER: Penetrating Barriers - Enhancing Molecular Transport into Complex Biological Membranes and Encouraging Students in STEM

Kansas State University, Manhattan KS

Investigators

Abstract

This project is jointly funded by the Chemistry of Life Processes in the Chemistry Division and by the Established Program to Stimulate Competitive Research (EPSCoR). In this CAREER project, Dr. Ryan J. Rafferty at Kansas State University focuses on the design of molecules that can cross biological barriers. Living organisms make use of barriers for defense against foreign substances and to control the transport of chemical substances. Two examples of such barriers are the blood-brain barrier and the membrane of gram-negative bacteria. Dr. Rafferty synthesizes molecules that have multiple, different chemical functional groups that influence the transport properties of various species through membranes. The research aims to identify systematic approaches for the design and synthesis of new classes of "universal" molecular transporters that can carry other molecules through biological barriers. For example, the new transporters could deliver imaging agents to explore the structure and function of the brain or therapeutic agents into disease-causing bacteria. The educational plan is designed to lower the barriers to broader participation in STEM fields. Dr. Rafferty uses research topics as examples of real-world applications in undergraduate chemistry classes. Public outreach is incorporated as a major teaching strategy in a new undergraduate/graduate Chemical Biology course. The broader outreach plan draws high school students to science through the K-State Annual Chemistry & Physics Symposium and Summer Research Bootcamps. The general public is engaged in this research through the Flint Hills Discovery Center. The movement of compounds across the complex biological membranes of gram-negative bacteria and the blood-brain barrier has been shown to be highly dependent upon physicochemical properties of the molecular transporters. However, the effects of individual physicochemical or spatial properties on transport across these barriers have not been systematically studied. The goal of this research project is to develop new chaperone-like small molecules (CLSMs) that facilitate general transport across complex biological barriers. To do so, Dr. Rafferty develops new molecular scaffolds as well new chemical screening libraries to explore single and combinational physicochemical properties. He also correlates these properties to the transport functions of the new molecules across blood-brain barrier and/or gram-negative bacteria. For example, the new transporters could deliver imaging agents to explore the structure and function of the brain or therapeutic agents into disease-causing bacteria. The research is well suited to the education and training of a diverse group of students and scholars. The Rafferty lab pursues activities that raise the awareness of the public of the value of science and research and that attract new students into the STEM fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.