RIG: Co-orthologous ABC Transporters: Shared Motifs, Shared Function?

本研究的目的是进一步表征拟南芥ABC转运基因AtWBC19，这是已知的第一个赋予抗生素抗性的植物基因，并将研究扩展到其最接近的同源物。AtWBC19是植物特异性基因家族的成员，该家族包括8个拟南芥和5个水稻同源基因；目前只知道AtWBC19的功能。由于基因家族的功能分化和特化通常是通过适应性进化发生的，我们假设该分支的几个成员参与了天然生物活性化合物的解毒。此外，在进化分支中所有转运体中存在保守基序，表明它们具有共同的调控机制和共同的广泛功能。为了验证这一假设，将以AtWBC19为模型，描述保守基序的重要性，并评估共同源基因之间的功能保守程度，位点定向诱变和酵母中的异源表达。就更广泛的影响而言，该项目提供了两个将研究与教学联系起来的主要机会。首先，该研究项目将用于埃默里大学（Emory University）的一门关于转运体的课程。这不仅是一项新举措，而且恰逢学院课程正在进行重大修订，更加强调将研究与教学联系起来；转运蛋白的研究对于那些希望更深入地研究生物学许多领域的学生来说是一项重要的努力。第二，将实施若干举措，以吸引和提供机会给学生，特别是代表性不足的少数民族，从事研究。将与亚特兰大大都会地区的院校（即斯派曼学院、莫尔黑德学院、州立堡谷大学）建立合作伙伴关系，从代表性不足的群体中招收至少4名学生。这个目标是可以实现的，因为埃默里大学已经有一个项目，埃默里大学暑期本科生研究项目（SURE），这有助于确定合适的导师/学生。

The goal of this research is to further characterize an Arabidopsis ABC transporter gene, AtWBC19, which is the first plant gene known to confer antibiotic resistance, and extend the investigation to its closest homologues. AtWBC19 is a member of a plant-specific gene family that includes 8 Arabidopsis and 5 rice coorthologous genes; only the function of AtWBC19 is known. Since functional divergence and specialization in gene families generally occur via adaptive evolution, we hypothesize that several members of this clade are involved in the detoxification of natural bioactive compounds. Moreover, the presence of conserved motifs among all transporters in the clade suggests common regulatory mechanisms as well as a common broad function. To test this hypothesis, delineate the significance of the conserved motifs, and assess the extent of function conservation among co-orthologous genes, site directed mutagenesis, and heterologous expression in yeast will be carried out using AtWBC19 as a model.In terms of broader impacts, the project provides two major opportunities to link research and teaching. First, the research project will be used to teach a course on transporters at Emory University. This is not only new, but comes at a time when the departmental curriculum is being significantly revised towards a stronger emphasis on linking research to teaching; the study of transporters is a critical endeavor for students who wish to pursue many areas of biology in greater depth. Second, several initiatives will be implemented to attract and provide opportunities for students, specifically under-represented minorities, to engage in research. Partnerships will be developed with institutions in the larger Atlanta metro area (i.e. Spellman College, Morehead College, Fort Valley State University) to recruit at least 4 students from underrepresented groups. This goal is obtainable because a program, Summer Undergraduate Research Program at Emory (SURE), is already in place at Emory University, which facilitates the identification of suitable mentors/students.