Biomaterials Presenting Antimicrobial Peptides

智力优势：抗菌肽（AMPs）是在所有生命系统中发现的小蛋白质。作为先天免疫系统的一部分，它们能有效对抗多种病原体。由于AMPs来源于宿主组织，并且具有非特异性的杀菌机制，因此具有作为新型药物的潜力。它们在体外对细菌的作用通常不如在体内有效，有时它们对宿主组织有毒。在这里，我们假设amp在生物相容性材料上的适当呈现和定位将增加它们对病原体的效力并限制对宿主细胞的毒性。目标是开发纳米级表面呈现AMP，并使用这些系统来量化抗菌活性和宿主细胞毒性对AMP的反应。进一步的目标是用amp修饰胶原蛋白，目前胶原蛋白被广泛用作生物相容性表面涂层。更广泛的目标是创造生物材料，模拟amp对病原体的体内呈现。重点研究了人眼表上皮细胞表达的三种amp。这些物种将通过控制密度、间距和纳米尺度的图案附着在生物相容性材料上，以研究局部AMP浓度和图案对杀微生物活性和角膜上皮细胞毒性的影响。提出的研究利用了一种新的方法，可以精确地控制amp在以前无法获得的尺寸上的呈现。它将允许量化微生物杀灭效果和宿主细胞毒性，以响应纳米级amp的呈现。更广泛的影响：提出的工作旨在直接改善隐形眼镜的制造，以抑制眼睛感染。除了这些和其他可能从这项工作中出现的新型抗菌装置外，该项目还将对AMP破坏细菌膜的机制以及AMP浓度和协同性在决定其活性中的作用产生新的基本见解。该研究项目将为本科生、研究生和博士后水平的学生提供跨学科的研究经验。PI将与休斯敦大学成功的少数族裔外展项目合作，在休斯敦地区的高中开展。他还计划与德克萨斯南方大学（Texas Southern University）建立一个本科生暑期实习项目，这是一所历史上的少数族裔大学，位于休斯顿大学（University of Houston）附近。菲德学校与泽维尔大学、Prairie View a&m和德克萨斯南方大学建立了合作关系，为女性和少数民族提供研究和教育项目。

INTELLECTUAL MERIT: Antimicrobial peptides (AMPs) are small proteins found in all living systems. As a part of the innate immune system, they are potent against a broad spectrum of pathogens. Because they are derived from host tissue and have a non-specific mechanism of killing bacteria, AMPs have potential as novel pharmaceutical agents. They are often not as effective against bacteria in vitro as they are in vivo, and sometimes they are toxic to the host tissue. Here it is hypothesized that proper presentation and localization of AMPs onto biocompatible materials will increase their potency against pathogens and limit toxicity toward host cells in vitro. The objectives are to develop nanoscale-patterned surfaces presenting AMPs and to use these systems to quantify the antimicrobial activity and host cell toxicity in response to AMP presentation. A further objective is to modify collagen, currently in wide use as a biocompatible surface coating, with AMPs. The broader objective is to create biomaterials that mimic the in vivo presentation of AMPs to pathogens. The focus is on three AMPs expressed by human ocular surface epithelia. These species will be attached to biocompatible materials with control over density, spacing, and nanoscale patterning to investigate the effect of local AMP concentration and patterning on microbiocidal activity and corneal epithelial cell toxicity. The proposed research capitalizes on a new means of precisely controlling the presentation of AMPs on a size scare not previously available. It will allow quantification of microbiocidal effectiveness and host cell toxicity in response to nanoscale presentation of AMPs. BROADER IMPACTS: The proposed work is aimed directly at improvements in contact lens fabrication to inhibit eye infections. In addition to these and other novel antimicrobial devices that might emerge from this work, the project will yield new fundamental insights into the mechanism by which AMPs disrupt the bacterial membrane and the role of AMP concentration and cooperativity in determining their activity. The research program will provide interdisciplinary research experience for undergraduate, graduate, and postdoctoral level students. The PI will team with successful University of Houston minority outreach programs to Houston area high schools. He also plans to establish an undergraduate summer internship program with Texas Southern University, a historically minority university located near the University of Houston. Feeder school relationships with Xavier University, Prairie View A&M, and Texas Southern exist to provide research and educational programs accessible to women and minorities.