CAREER: Functional Scaffolds for Polymeric Antimicrobial Agents

ID: MPS/DMR/BMAT(7623) 0845592 PI: Kuroda， Kenichi ORG: michigan标题：职业：高分子抗菌剂的功能支架该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力优势：该项目的长期目标是开发新的广谱抗菌药物。该研究的核心假设是，预组装膜活性聚合物链将增强它们的协同穿膜能力，从而导致与单线聚合物链相比抗菌效力的增加。这项研究将集中在星形和束状聚合物的创造上，这些聚合物包含多个聚合物链组装在一个核心分子上，从而预先确定每一类聚合物的几何特征。通过利用复杂的大分子框架，PI试图了解这些三维支架如何影响与细胞膜相互作用的功能，并利用这些知识进一步合理设计用于临床和医学用途的合成生物材料。此外，这些结构的使用提供了一个独特的机会，不仅可以专门调整聚合物臂的显示以创建最佳的裂解剂，而且还可以更广泛地为膜活性化合物的作用机制提供新的见解。由于抗菌肽和聚合物的一般机制仍然存在高度争议，部分原因是缺乏合适的工具提出了一个强大的实验障碍，这项工作将显著推进该领域。同样，这些研究对于提供聚合物-膜相互作用的详细理解，提高我们合理设计和设计聚合物抗菌剂的进一步迭代的能力将是无价的。更广泛的影响：拟议研究的跨学科性质将为PI的学生和博士后提供重要的教育机会。s和PI？合作者?实验室。学生将在期刊俱乐部中探索广泛的相关文献，这将巩固他们对实验室工作的理论理解。PI还致力于提高他直接监督之外的学生的知识；与PI一致吗？根据目前的研究，抗生素耐药性和材料毒性的主题将被纳入PI在密歇根大学牙科学院教授的生物材料课程中。放眼全球，PI与日本名古屋大学的研究小组开展了几项国际研究合作。这些互动不仅可以让学生直接从世界专家那里获得科学知识，而且还可以获得对科学实践的宝贵见解，特别是那些能够参加我们新的国际学生交流计划的学生。最后，PI致力于为各种各样的学生提供这些和类似的有吸引力的研究机会，并期待他继续参与密歇根大学的本科生和代表性不足的学生项目。

ID: MPS/DMR/BMAT(7623) 0845592 PI: Kuroda, Kenichi ORG: MichiganTitle: CAREER: Functional Scaffolds for Polymeric Antimicrobial AgentsThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: The long-term goal of this project is to develop new, broad-spectrum antimicrobial agents. The central hypothesis is that the preassembly of membrane-active polymer chains will enhance their cooperative ability to perforate the membrane, leading to an increase in antimicrobial potency as compared to single linear polymer chains. The study will focus on the creation of star- and bundle-shaped polymers that contain multiple polymer chains assembled onto a core molecule, thus presetting the geometrical features for each class of polymers. By utilizing complex macromolecular frameworks, the PI seeks to understand how these three-dimensional scaffolds can influence function in interactions with cell membranes, and to use this knowledge in the further rational design of synthetic biomaterials for clinical and medicinal uses. Additionally, the use of these architectures provides a unique opportunity to not only specifically tune the display of polymer arms to create optimal lytic agents, but also to provide novel insight into the mechanism of action of membrane-active compounds more broadly. As the general mechanism of antimicrobial peptides and polymers remains highly controversial, in part because the lack of suitable tools presents a formidable experimental roadblock, this work will significantly advance the field. Similarly, these studies will be invaluable in providing a detailed understanding of polymer-membrane interactions, improving our ability to rationally design and engineer further iterations of polymeric antimicrobial agents. BROADER IMPACTS: The interdisciplinary nature of the proposed research will provide an important educational opportunity for the students and postdoctoral fellows in the PI?s and the PI?s collaborators? labs. The students will explore a broad range of relevant literature in journal clubs that will cement their theoretical understanding of their efforts in the laboratory. The PI is also dedicated to improving the knowledge of students outside of his direct supervision; in line with the PI?s current research, the topics of antibiotic resistance and toxicity of materials will be incorporated into the Biomaterials course that the PI teaches in the University of Michigan School of Dentistry. Looking even more globally, the PI has initiated several international research collaborations with research groups at Nagoya University in Japan. These interactions will allow students not only to gain scientific knowledge directly from world experts, but also to obtain valuable insight into the scientific practices, particularly for those students who are able to take part in our new international student exchange program. Finally, the PI is committed to providing these and similarly engaging research opportunities for a variety of students, and looks forward to his continued participation in the University of Michigan programs for undergraduate and underrepresented students.