NSF/FDA SIR: Using Microbial Signaling Systems to Understand Relationship Between Microbial Growth an d Breast Implant Complications

NSF/FDA SIR：利用微生物信号系统了解微生物生长与乳房植入物并发症之间的关系

• 批准号: 2037572
• 负责人: Jeseth Delgado Vela
• 金额: $ 5万
• 依托单位: Howard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2037572&HistoricalAwards=false
• 关键词: NSF; FDA; SIR; Using; Microbial

Breast augmentation is one of the most popular surgical cosmetic procedures nationwide, with over $1.1 billion spent on silicone gel implants in 2018. However, breast implants are not lifetime devices and the longer patients have breast implants, the higher the risk of complications. Recent studies show that biofilms, microbial communities that grow on surfaces, are associated with these complications. At the center of the discussion is BIA-ALCL (breast implant-associated anaplastic large cell lymphoma/cancer) which recently triggered a series of regulatory actions worldwide. Recent studies suggest that the higher surface area of textured implants provide more opportunity for bacteria to colonize into biofilms, which could stimulate a cascade of immune responses including chronic inflammation, one of the possible pathogenesis of BIA-ALCl. The goal of this one-year Scholar-in-Residence project is to study the impact of a special set of molecules known to regulate bacteria activity, termed “quorum sensing molecules," on BIA-ALCL. The project’s findings are expected to provide information that aids in the review of new strategies to control and inhibit bacterial infection in breast implants. These findings will also be integrated into existing K-12 outreach activities occurring at Howard Middle School. This proposed research will support a female graduate student from Howard University engaged in highly interdisciplinary research and a new collaboration between Howard University and the Food and Drug Administration.This project is focused on the impact of quorum sensing (QS) molecules on BIA-ALCL. Microbial communities use QS molecules to coordinate microbial community function. QS molecules are often used to regulate biofilm formation and can be associated with a T-Cell response in certain types of organisms, though current knowledge on immune response to QS molecules is nascent. The research plan is designed to advance knowledge on the link between microbial community quorum sensing capacity and malignancies. The central hypothesis of this work is that QS can regulate biofilm formation in textured implants. The investigators will employ bioinformatic, experimental, and computational models to assess this hypothesis with three objectives: (1) Conduct a review and bioinformatic analysis on breast implant microbiota, (2) Develop a drip flow biofilm reactor system to evaluate how biofilms response to molecular cues, and (3) Develop a computational model system to evaluate how biofilms respond to material cues. The expected outcome is an understanding of differences in the microbial structure and function as it relates to quorum sensing capacity in implants of different patients. The bioinformatics analysis could serve as a case study on how to utilize high-throughput tools to facilitate regulatory review of permanent implants. The model system will provide information that aids in the review of new strategies to control and inhibit bacterial infection in breast implants.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.

隆胸是全国最受欢迎的外科美容手术之一，2018年在硅凝胶植入物上花费了超过11亿美元。然而，乳房植入体不是终身设备，患者使用乳房植入体的时间越长，并发症的风险就越高。最近的研究表明，生物膜，表面上生长的微生物群落，与这些并发症有关。讨论的中心是BIA-ALCL（乳腺植入物相关的间变性大细胞淋巴瘤/癌症），最近在全球范围内引发了一系列监管行动。最近的研究表明，毛面植入物的更高表面积为细菌定植到生物膜中提供了更多机会，这可能刺激一系列免疫反应，包括慢性炎症，这是BIA-ALCl的可能发病机制之一。 这个为期一年的驻校学者项目的目标是研究一组已知调节细菌活性的特殊分子（称为“群体感应分子”）对BIA-ALCL的影响。 该项目的研究结果有望提供信息，有助于审查控制和抑制乳房植入体细菌感染的新策略。这些调查结果也将被纳入现有的K-12外展活动发生在霍华德中学。这项研究将支持霍华德大学的一名女研究生从事高度跨学科的研究，以及霍华德大学和美国食品药品监督管理局之间的一项新合作。该项目的重点是群体感应（QS）分子对BIA-ALCL的影响。微生物群落利用QS分子协调微生物群落功能。QS分子通常用于调节生物膜的形成，并且可以与某些类型的生物体中的T细胞应答相关，尽管目前关于对QS分子的免疫应答的知识是新生的。该研究计划旨在提高对微生物群落群体感应能力与恶性肿瘤之间联系的认识。这项工作的中心假设是，QS可以调节毛面种植体中的生物膜形成。研究人员将采用生物信息学、实验和计算模型来评估这一假设，目标有三个：（1）对乳房植入体微生物群进行审查和生物信息学分析，（2）开发滴流生物膜反应器系统，以评估生物膜如何对分子线索做出反应，以及（3）开发计算模型系统，以评估生物膜如何对材料线索做出反应。预期的结果是了解微生物结构和功能的差异，因为它涉及到不同患者植入物的群体感应能力。 生物信息学分析可以作为如何利用高通量工具促进永久性植入物监管审查的案例研究。该模型系统将提供信息，帮助审查新的战略，以控制和抑制细菌感染的乳房implants.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。