A “Focused Research Organization” to Reduce Antibiotic Resistance In Aquaculture
Research and engineering to reverse antibiotic resistance in aquatic bacteria, through the application of a well-validated CRISPR-based genetic system, can help catalyze safer, more sustainable land-based aquaculture as a nutritious and affordable food source.
问题陈述
不断增长的人口需要负担得起的健康蛋白质来源。由于过度捕捞对全球鱼类库存施加了巨大压力，Aquafarming提出了潜在的选择。美国目前进口其海鲜的80％，大多数进口是由外国水产养殖生产的。扩大国内水产养殖可能有助于消除170亿美元的海鲜贸易赤字。但是，国内水产品构成了自己的挑战，包括在基于海洋的行动附近的环境污染的潜力。在这种情况下，网状区域内的高浓度鱼会导致细菌和其他废物污染在鱼类限制范围之外传播。在孤立的内陆围墙中饲养鱼的另一种策略可能会带来较小的环境风险，但也需要维持水质，频繁的水过滤，并且通常使用高抗生素浓度来减轻细菌性鱼类病原体，这些病原体在这种人行过的条件下繁殖。实际上，在鱼类生长的最后几周中，水水船经常试图降低添加到水中的抗生素水平，以将其浓度降低到商业鱼类的强制性健康标准之下，但是这些努力仅部分有效，并造成了巨大的后勤负担。
项目概念
我们提出了遗传系统的发展，以降低陆基水疗围栏中抗生素耐药性的流行。我们将开发出无害的环境细菌菌株，能够将自我复印的遗传盒转移到水产养殖中关注的致病细菌菌株中。通过这些菌株，我们旨在减少高密度鱼外壳中这些细菌病原体的毒力，并擦洗其抗生素耐药性。
该项目的核心是将被称为原核激活遗传学（Pro-AG）的验证良好的自我扩增的遗传系统应用于水产养殖设施中细菌病原体中擦洗毒力和抗生素抗性因子的任务。自从发表开创性研究的发表以来，描述了这种基于CRISPR的系统，用于逆转抗生素耐药性（Valderrama等，2019，Nat. Comm.10，5726），通过将其与通过水平转移系统（例如结合传递元件或噬菌体）之间扩散的方法相结合，我们进一步推进了Pro-Ag平台。我们还将新的遗传特征纳入了Pro-Ag工具包中，包括一个系统，以清洁有效地删除遗传元素，例如负责抗生素耐药性的毒力因子。在这些核心成就的基础上，我们将把亲框架和基于噬菌体的新型系统转移到水产养殖引起的几种细菌菌株中，目的是降低其抗生素耐药性（AR）基因和毒力潜力。
What is a Focused Research Organization?
专注的研究组织（FROS）are time-limited mission-focused research teams organized like a startup to tackle a specific mid-scale science or technology challenge. FRO projects seek to produce transformative new tools, technologies, processes, or datasets that serve as public goods, creating new capabilities for the research community with the goal of accelerating scientific and technological progress more broadly. Crucially, FRO projects are those that often fall between the cracks left by existing research funding sources due to conflicting incentives, processes, mission, or culture. There are likely a large range of project concepts for which agencies could leverage FRO-style entities to achieve their mission and advance scientific progress.
This project is suited for a FRO-style approach出于三个原因。首先，为这项工作吸引风险投资或行业资金将非常困难。对于大多数希望看到投资回报率较短的视频（按2 - 3年的订单）来说，预期的时间表太长了。其次，该项目具有很大的技术风险，因为我们不知道在密集的鱼类封装的大型外壳的背景下，这是任何抗菌干预措施的艰巨环境。第三，仅通过对学术科学支持的标准支持渠道获得的项目的实验室部分的规模超过了通常可用的资金水平，因为需要对几种不同种类的鱼类病原体进行专业交付系统的平行设计。与许多许多学术研究计划相比，这还需要更多的“应用”工作。由于这些原因，该项目非常适合来回的最佳地点。
该项目将如何受益科学进步
If successful, our systems would greatly reduce the necessary frequency and concentrations of antibiotics to control bacterial fish pathogens. Solving or attenuating this central challenge to land-based aquaculture should help foster safe, sustainable and affordable sources of nutritious, uncontaminated fresh fish and help catalyze a shift away from unsustainable overfishing practices in the open ocean and environmentally hazardous practices in ocean-based aquafarms. This project could also have broader knock-on effects by enabling similar technical advances to reduce antibiotic resistance prevalence in other environmental settings (e.g., livestock, sewage treatment), which are also substantial sources of worldwide antibiotic resistance.
关键联系人
作者
- UCSD的Ethan Bier博士，ebier@ucsd.edu
反向链接
- Matt Hourihan, Federation of American Scientists,mhourihan@www.tumejico.com
- 美国科学家联合会爱丽丝·吴（Alice Wu）原子量单位@www.tumejico.com。
Learn more about FROs, and see our full library of FRO project proposals here.
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