Doctoral Dissertation Research: Tracing the origin of infectious disease: A comparative paleogenomics study of Treponema pallidum

博士论文研究：追踪传染病的起源：梅毒螺旋体的比较古基因组学研究

• 批准号: 1919662
• 负责人: George Perry
• 金额: $ 3.2万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1919662&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Tracing; origin

Syphilis is a sexually transmitted infection (STI) caused by Treponema pallidum subp. pallidum bacteria. It has recently reemerged as an urgent worldwide health crisis. The origin of the disease has been a mystery since its sudden appearance in Europe at the end of the 15th century and its subsequent rapid global spread. It has long been debated whether syphilis was introduced to Europe, perhaps from the Americas, or evolved from a form of treponemal infection that had been in Europe all along. Graduate student Ziyu Wang and collaborators at The Pennsylvania State University will take a multi-faceted approach to investigate the pathogen's genetic diversity over the past 500 years in Europe to explore several possibilities to explain syphilis' origin in Europe. The current T. pallidum pathogens - associated with several related diseases - likely represent only the most successful or recently emerged genetic variants. Examined through an anthropological lens, ancient genomes when considered within the context of human sociocultural systems yield clues about the processes through which pathogens have achieved their evolutionary success. Ultimately a more informed understanding of the factors that contribute to the complex and dynamic interactions between humans and their pathogens provides a deep-time foundation for predicting the evolutionary trajectories of modern infectious pathogens and human responses. Today, as in the past, STI-related stigma has done much to interfere with the development and implementation of effective intervention programs. Lessons learned from historic epidemics and the public response will provide valuable tools for training healthcare professionals, STI high-risk groups, and the public.To untangle syphilis' origin, its evolution, and its worldwide spread, the research team will sequence T. pallidum genomes from representative specimens sampled from temporally and socially well-characterized European skeletal assemblages dating to the 16th to 19th centuries. Ancient T. pallidum has previously not been well studied because of the limited ability of conventional genetic techniques (e.g., polymerase chain reaction) to recover highly-degraded ancient pathogen DNA. Here a sensitive targeted hybridization capture technique will be used to recover complete, or near-complete, ancient T. pallidum genomes. By comparing temporally known ancient pathogen genomes with their modern equivalents, the research team can track the sequential changes that occurred in the pathogen's genetic history. Doing so will narrow the possible evolutionary scenarios for the origin of syphilis and point to when the pathogen variant that causes syphilis first emerged.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.

梅毒是由Treponema Pallidum Sump引起的性传播感染（STI）。粒细菌。最近，它重新出现为全世界的紧急健康危机。自从15世纪末在欧洲突然出现以来，该疾病的起源一直是一个谜，随后迅速的全球传播。长期以来，人们一直在争论梅毒是是从美洲引入欧洲的，还是从一直以来一直在欧洲一直在欧洲的一种形式的treponemal感染而发展。 宾夕法尼亚州立大学的研究生Ziyu Wang和合作者将采用多方面的方法来调查欧洲过去500年来病原体的遗传多样性，以探索几种可能性来解释梅毒在欧洲起源的可能性。当前与几种相关疾病相关的当前T. pallidum病原体可能仅代表最成功或最近出现的遗传变异。通过人类学晶状体检查，当在人类社会文化系统的背景下考虑时，古代基因组就产生了有关病原体取得进化成功的过程的线索。最终，人们对有助于人类与病原体之间复杂而动态相互作用的因素有了更明智的理解，为预测现代传染病和人类反应的进化轨迹提供了深刻的基础。如今，与过去一样，与STI相关的污名在干扰有效干预计划的制定和实施方面做了很多事情。从历史流行病和公众反应中学到的经验教训将为培训医疗保健专业人员，高风险群体和公众提供有价值的工具。为了解开梅毒的起源，其进化和全球范围的传播，研究团队将对来自代表性的pallidum基因组进行序列，从代表性的标本中取得了时间和社会良好的欧洲序列，以供欧洲良好的欧洲供应，以供欧洲良好的欧洲序列供应，以供欧洲融合式欧洲。由于传统的遗传技术（例如聚合酶链反应）能够恢复高度脱落的古代病原体DNA，因此古老的T. pallidum以前没有得到很好的研究。这里将使用一种敏感的靶向杂交捕获技术来恢复完整或近乎完整的古代T. pallidum基因组。通过将临时知名的古代病原体基因组与其现代等效物进行比较，研究团队可以跟踪病原体遗传史发生的顺序变化。这样做将范围缩小梅毒起源的可能进化方案，并指向导致梅毒首次出现的病原体变体何时出现。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估标准来通过评估来进行评估的。