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

该项目由化学部门的生命过程化学和刺激竞争研究的既定计划（EPSCoR）共同资助。在这个CAREER项目中，堪萨斯州立大学的Ryan J. Rafferty博士专注于设计能够跨越生物屏障的分子。生物利用屏障防御外来物质和控制化学物质的运输。这种屏障的两个例子是血脑屏障和革兰氏阴性细菌的膜。拉弗蒂博士合成了具有多种不同化学官能团的分子，这些分子可以影响各种物质通过膜的运输特性。该研究旨在确定设计和合成新型“通用”分子转运体的系统方法，这些转运体可以通过生物屏障携带其他分子。例如，新的转运体可以运送成像剂来探索大脑的结构和功能，或者将治疗剂运送到致病细菌中。该教育计划旨在降低更广泛参与STEM领域的障碍。Rafferty博士在本科化学课上使用研究课题作为实际应用的例子。在新的本科/研究生化学生物学课程中，公众宣传被纳入主要的教学策略。更广泛的推广计划通过K-State年度化学与物理研讨会和夏季研究训练营吸引高中生参与科学。公众通过弗林特山探索中心参与这项研究。化合物穿过革兰氏阴性细菌的复杂生物膜和血脑屏障的运动已被证明高度依赖于分子转运体的物理化学性质。然而，个体物理化学或空间性质对跨越这些屏障的运输的影响尚未得到系统的研究。本研究项目的目标是开发新的伴侣样小分子（CLSMs），促进跨越复杂生物屏障的一般运输。为此，Rafferty博士开发了新的分子支架以及新的化学筛选库，以探索单一和组合的物理化学性质。他还将这些特性与新分子穿越血脑屏障和/或革兰氏阴性细菌的运输功能联系起来。例如，新的转运体可以运送成像剂来探索大脑的结构和功能，或者将治疗剂运送到致病细菌中。这项研究非常适合不同学生和学者群体的教育和培训。拉弗蒂实验室开展的活动旨在提高公众对科学和研究价值的认识，并吸引新生进入STEM领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.