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

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是通过利用皮肤微生物组中存在的天然驱蚊化合物开发安全，天然，持久和有效的驱蚊产品。 蚊子传播的疾病影响全球7亿人，每年造成数百万人死亡。 基孔肯雅热、西尼罗河、疟疾、寨卡病毒、登革热，只是蚊子传播的一些使人衰弱的媒介。蚊子引起的疾病每年花费68亿美元，驱蚊剂市场为32亿美元，并且还在增长。许多解决方案旨在杀死和禁用蚊子，但蚊子是生态食物链的重要组成部分。此外，许多驱虫剂都是剧毒的，蚊子正在产生抗药性。该技术将用于识别将驱动内源性皮肤微生物组更具驱蚊性表型的化合物。使用这些方法，可以利用天然皮肤微生物组中包含的生物化学来产生内源性驱避性，这是一种安全，天然，环保和有效的蚊子屏障。预计这种驱虫方法甚至可以安全地用于儿童和孕妇。此外，还可以利用这种方法开发多种昆虫的驱避剂、伴侣动物的驱避产品以及其他非处方皮肤产品。SBIR第一阶段项目的智力价值是通过影响皮肤微生物组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，该平台技术用于识别由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靶向其最终产物包含天然驱蚊化合物的那些途径。我们的目标是创造一种局部驱蚊产品。对于这个项目，计划是完成对从自然排斥或吸引按蚊（携带疟疾的蚊子）的个体收集的皮肤样本的宏基因组测序。下一步是预测代谢物化合物的周转率，并使用代谢组学来验证结果。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.