SBIR Phase I: Enhancing the skin microbiome for mosquito repellency: Next generation mosquito repellent derived from big data analysis

这个小型企业创新研究(SBIR)项目的更广泛影响/商业潜力是开发一种安全、天然、持久和有效的驱蚊产品，方法是利用皮肤微生物群中存在的天然驱蚊化合物。蚊子传播的疾病影响着全球7亿人，每年导致数百万人死亡。基孔肯雅、西尼罗河、疟疾、寨卡、登革热只是蚊子传播的一些令人衰弱的媒介。蚊子引发的疾病每年花费68亿美元，驱蚊剂的市场价值为32亿美元，而且还在不断增长。许多解决方案旨在杀死和禁用蚊子，但蚊子是生态食物链中至关重要的一部分。此外，许多驱蚊剂是剧毒的，蚊子正在产生抗药性。这项拟议的技术将被用来识别将驱动内源性皮肤微生物群变得更具驱蚊表型的化合物。使用这些方法，有可能利用天然皮肤微生物群中包含的生化物质来创造一种安全、自然、环保和有效的蚊子屏障。预计这种驱避方法甚至可以安全地用于儿童和孕妇。此外，可以使用这种方法开发多种昆虫的驱避剂、同伴动物的驱避剂和更多的非处方药皮肤产品。SBIR第一阶段项目的智力价值是通过影响皮肤微生物群的驱避性来开发一类新的局部驱虫剂。这将通过开发和验证一种平台技术来实现，该平台技术可以识别微生物组产生的与感兴趣的生化途径相关的化合物，并使用所识别的化合物来针对其最终产品包括天然驱蚊化合物的那些途径。其目标是创造一种局部驱蚊产品。对于这个项目，计划完成从自然排斥或吸引按蚊(携带疟疾的蚊子)的个体身上收集的皮肤样本的元基因组测序。下一步是预测代谢物化合物的周转，并使用代谢组学来验证结果。体外测试和计算机模型将被用来为使用这些预测的化合物来诱导微生物群产生驱蚊代谢物提供概念验证。这一奖项反映了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。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a safe, natural, long-lasting and effective mosquito repellent product by exploiting the natural repellent compounds present in the skin microbiome. Mosquito-borne illnesses affect 700M people worldwide and cause several million deaths each year. Chikungunya, West Nile, Malaria, Zika, Dengue, are just some of the debilitating vectors spread by mosquitoes. Mosquito-derived diseases cost $6.8B/year and the market for mosquito repellents is $3.2B and growing. Many solutions are aimed at killing and disabling mosquitoes, but mosquitoes are a crucial part of the ecological food chain. Further, many repellents are extremely toxic, and mosquitoes are developing resistance. The proposed technology will be used to identify compounds that will drive the endogenous skin microbiome to a more mosquito repellent phenotype. Using these methods, it is possible to harness the biochemistry contained in the native skin microbiome to create an endogenous repellency that is a safe, natural, environmentally friendly, and effective barrier to mosquitoes. It is expected that this repellency approach may be used safely even with children and pregnant women. In addition, it may be possible to use this approach to develop repellents for multiple insects, repellent products for companion animals, and additional over-the-counter skin products.The intellectual merit of this SBIR Phase I project is to develop a new class of topical insect repellents by influencing repellency in the skin microbiome. This will be accomplished by developing and validating a platform technology to identify compounds produced by the microbiome that are associated with biochemical pathways of interest, and use the identified compounds to target those pathways whose end-products comprise natural mosquito-repellent compounds. The goal is to create a topical mosquito repellent product. For this project, the plan is to complete metagenome sequencing on skin samples collected from individuals that are either naturally repellent or attractive to Anopheles mosquitoes (the mosquito that carries Malaria). The next step is to predict metabolite compound turnover and use metabolomics to validate the results. In vitro assays and in silico models will be used to provide proof-of-concept for the use of those predicted compounds to induce the microbiota to produce mosquito repellent metabolites.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.