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

隆胸是全国最受欢迎的整形手术之一，2018年在硅胶植入物上花费了超过11亿美元。然而，隆胸并不是终生设备，患者隆胸的时间越长，并发症的风险就越高。最近的研究表明，生物膜，即生长在表面的微生物群落，与这些并发症有关。讨论的中心是BIA-ALCL(乳房植入相关间变性大细胞淋巴瘤/癌症)，它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，纹理种植体的较高表面积为细菌在生物膜中定植提供了更多的机会，这可能会刺激包括慢性炎症在内的一系列免疫反应，这可能是BIA-ALCL的发病机制之一。这个为期一年的常驻学者项目的目标是研究一组已知的调节细菌活动的特殊分子，称为“群体感应分子”，对BIA-ALCL的影响。该项目的发现有望提供有助于审查控制和抑制乳房植入物细菌感染的新策略的信息。这些调查结果还将纳入霍华德中学现有的K-12外展活动。这项拟议的研究将支持一名来自霍华德大学的女研究生从事高度跨学科的研究，以及霍华德大学和食品和药物管理局之间的一项新合作。该项目专注于群体感应(QS)分子对BIA-ALCL的影响。微生物群落利用QS分子来协调微生物群落的功能。QS分子经常被用来调节生物膜的形成，在某些类型的生物体中可以与T细胞反应有关，尽管目前对QS分子的免疫反应的了解还处于萌芽状态。该研究计划旨在促进对微生物群落群体感应能力与恶性肿瘤之间联系的了解。这项工作的中心假设是QS可以调节纹理植入物中生物膜的形成。研究人员将使用生物信息学、实验和计算模型来评估这一假设，目标有三：(1)对乳房植入物微生物区系进行综述和生物信息学分析；(2)开发滴流生物膜反应器系统，以评估生物膜对分子线索的反应；以及(3)开发计算模型系统，以评估生物膜对材料线索的反应。预期的结果是了解微生物结构和功能的差异，因为它与不同患者植入物的群体感应能力有关。生物信息学分析可以作为一个案例，研究如何利用高通量工具来促进对永久性植入物的监管审查。该模型系统将提供有助于审查控制和抑制乳房植入物细菌感染的新策略的信息。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。

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.