Using genomics to understand Salmonella transmission from farm-to-fork and the environment in the Philippines

目前和新出现的人类感染中有60%以上是人畜共患，即在动物和人之间传播，具有“同一健康”影响。沙门氏菌感染是一个重大的健康负担，每年有多达1.83亿例病例和140万人死亡。令人担忧的是，抗生素耐药性的上升正在急剧加剧沙门氏菌感染的风险，对一线药物具有耐药性的菌株在全球蔓延。全基因组测序（WGS）数据可以深入了解此类感染的传播和传播，以及抗生素耐药性的遗传基础，从而为卫生感染控制决策提供信息。拟议的博士项目最初将侧重于生成和分析从菲律宾各地的农场、市场和诊所收集的沙门氏菌的WGS数据，以了解基因组多样性、循环菌株类型（“血清型”）和抗生素耐药性变体以及传播途径。这些数据将与全球来源的公共序列结合起来，并随后在其他人群中进行抽样，包括在菲律宾境内。其他重要的一种健康病原体也将使用便携式平台（例如牛津纳米孔技术MinION）在研究地点进行测序，并开展相关的能力加强活动。该项目由OneZoo CDT资助，本质上是多学科的，跨越了潜在资助者（BBSRC， NERC和MRC）的权限。也就是说，该项目侧重于“微生物”（BBRSC）、“生态学、生物多样性和系统学”（NERC）以及“全球健康”和“感染与免疫”（MRC）。该项目涵盖了UKRI 5个战略主题中的3个：“建立一个安全和有弹性的世界”、“确保更好的健康、老龄化和福祉”和“应对感染”，以及跨理事会对“抗菌素耐药性”的兴趣。这个项目将利用我的微生物学和实验室技能，并涉及获得其他技能，如基因组学，大数据分析和流行病学，从而提供跨学科的经验，涉及实验室技能，数据和数字科学，这些都需要进行独立的基于基因组学的One health调查。培训将由LSHTM提供，包括实地实践、实验室和计算工作，以及直接从OneZoo CDT核心能力加强活动中提供。

More than 60% of current and emerging human infections have a zoonotic origin, that is, they are transferred between animals and people, and have "One health" impacts. Salmonella bacterial infections have a major one health burden, with up to 183 million cases and 1.4 million deaths each year. Worringly, the rise of resistance to antibiotics is acutely exacerbating the risk of Salmonella infections, with the global spread of strains that are resistant to frontline drugs. Whole genome sequencing (WGS) data can provide insights into the transmission and spread of such infectons, as well as the genetics underlying antibiotic resistance, thereby informing one health infection control decision making. The proposed PhD project will focus initially on generating and analysing WGS data for Salmonella collected from farms, markets and clinics (n>1,000) around the Philippines to understand genomic diversity, circulating strain-types ("serovars") and antibiotic resistance variants, and transmission pathways. These data will be contextualised with globally sourced public sequences, and subsequent sampling across other populations, including within The Philippines. Other important One health pathogens will also be sequenced across study sites using portable platforms (e.g., Oxford Nanopore Technology MinION), with associated capacity strengthening activities. This project is funded by the OneZoo CDT, and is multidisciplinary in nature, spanning the remits of the underlying funders (BBSRC, NERC, and MRC). Namely, the project focuses on "microbes" (BBRSC), "ecology, biodiversity, and systematics" (NERC), and "global health" and "infections and immunity" (MRC). This project covers 3 of the 5 UKRI strategic themes: "Building a secure and resilient world", "securing better health, ageing and wellbeing" and "tackling infections", as well as cross-council interests in "antimicrobial resistance".This project willl leverage off my microbiology and laboratory skillset, and involve the acquistion of other skills, such as genomics, big data analysis and epidemiology thereby providing a trandisciplinary experience involving skills in the laboratory, and data and digital sciences, which are needed to conduct independent genomics-based One health investigations. Training will be provided by the LSHTM, including through hands on field, laboratory and computational work, and directly from OneZoo CDT core capacity strengthening activities.