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

职业：突破障碍 - 增强复杂生物膜的分子运输并鼓励学生学习 STEM

基本信息

批准号：
1848186
负责人：
Ryan Rafferty
金额：
$ 62.5万
依托单位：
Kansas State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1848186&HistoricalAwards=false
关键词：
CAREER Penetrating Barriers Enhancing Molecular

项目摘要

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.

该项目由化学部生命过程化学和已建立的激励竞争性研究计划(EPSCoR)共同资助。在这个职业项目中，堪萨斯州立大学的瑞安·J·拉弗蒂博士专注于设计能够跨越生物屏障的分子。生物有机体利用屏障防御外来物质并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个不同化学官能团的分子，这些官能团会影响不同物种通过膜的运输特性。这项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，这些转运体可以携带其他分子穿过生物屏障。例如，新的转运体可以输送显像剂来探索大脑的结构和功能，或者将治疗剂注入致病细菌。该教育计划旨在降低更广泛参与STEM领域的门槛。拉弗蒂博士将研究课题作为本科生化学课程在现实世界中应用的例子。公众宣传被纳入新的本科生/研究生化学生物学课程中作为一项主要的教学策略。更广泛的外展计划通过K-State年度化学和物理研讨会和暑期研究训练营吸引高中生接触科学。公众通过弗林特山探索中心参与了这项研究。化合物通过革兰氏阴性细菌的复杂生物膜和血脑屏障的移动已被证明高度依赖于分子转运体的物理化学性质。然而，各个物理化学性质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。这一研究项目的目标是开发新的伴侣样小分子(CLSM)，以促进跨越复杂生物屏障的一般运输。为此，拉弗蒂博士开发了新的分子支架和新的化学筛选文库，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通过血脑屏障和/或革兰氏阴性细菌的运输功能联系起来。例如，新的转运体可以输送显像剂来探索大脑的结构和功能，或者将治疗剂注入致病细菌。这项研究非常适合对不同群体的学生和学者进行教育和培训。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，并吸引新学生进入STEM领域。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。