Molecular Co-Evolution: Lessons from Pathogen-Immune System Interactions

分子共同进化：病原体-免疫系统相互作用的教训

• 批准号: 1631719
• 负责人: Vijay Balasubramanian
• 金额: $ 0.6万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1631719&HistoricalAwards=false
• 关键词: Molecular; Co; Evolution; Lessons; Pathogen

The workshop titled, "Molecular coevolution: lessons from pathogen-immune system interactions", will be held on 11th-12th April 2016, at the Princeton Center for Theoretical Sciences (PCTS). It will bring together theoreticians and experimentalists who study adaptive immunity in vertebrates or in bacteria. Adaptive mechanisms for immunity have evolved to mount a flexible and diverse response and to counteract the rapid evolution of pathogens to enhance organismal survival. The participants of this program work at the cutting edge of research into such immune dynamics. The goal is to foster new collaborations that build and test predictive approaches to coevolution of pathogens and the immune system. Predictive modeling is an essential component for understanding the fundamental science of the immune system. Such basic science advances will eventually enable advances in medicine. Close to half of the participants in this workshop are females, helping to increase diversity and participation of women in STEM fields. The immune systems in vertebrates and in bacteria have evolved remarkable mechanisms for adapting to a diverse and constantly changing pathogenic environments. In vertebrates, new receptors are constantly generated by genomic recombination, and those that successfully detect threats are selectively amplified to protect the host. Some of the stimulated receptors are retained to form a memory of past infections, and thus to mount a rapid response against future infections of a similar type. This process of affinity maturation in an adaptive immune system constitutes a Darwinian evolution of the immune cells that occurs during the lifetime of an organism. By contrast, in some bacteria and archaea, immunity is directly acquired from interactions with the environment, and is heritable to future generations. These bacteria use the CRISPR-Cas mechanism to acquire specific genomic sequences from attacking phages (viruses that attack bacteria), and use these sequences to target future invaders. In both cases, the rapid turnover of pathogens to escape the adaptive immune response creates an evolutionary arms race at the molecular level. Understanding the complex dynamics of these adaptive immune systems in response to coevolving pathogens is only possible through a joint theoretical and experimental effort. This workshop will focus on a number of questions at this interface, including: (i) what does it mean for an immune repertoire to be "well-adapted", (ii) how can the actual dynamics of the adaptive system reach such a well-adapted state?, (iii) how should, and how does, the adaptive system react to an evolving pathogenic environment, and (iv) what are the molecular signatures of coevolution between viruses and the immune system, and how can we detect those from the biological data? This workshop will bring together many of the leading experts on these topics.

研讨会题为“分子共同进化：病原体-免疫系统相互作用的教训”，将于2016年4月11日至12日在普林斯顿理论科学中心（PCTS）举行。它将把研究脊椎动物或细菌适应性免疫的理论家和实验家聚集在一起。适应性免疫机制已经进化到能够产生灵活和多样化的反应，并抵消病原体的快速进化，以提高生物体的存活率。这个项目的参与者在研究这种免疫动力学的前沿工作。目标是促进新的合作，建立和测试病原体和免疫系统共同进化的预测方法。预测建模是理解免疫系统基础科学的重要组成部分。这些基础科学的进步最终将推动医学的进步。本次研讨会近一半的参与者是女性，这有助于提高女性在STEM领域的多样性和参与度。脊椎动物和细菌的免疫系统已经进化出了非凡的机制来适应多样化和不断变化的致病环境。在脊椎动物中，新的受体通过基因组重组不断产生，那些成功检测到威胁的受体被选择性地放大以保护宿主。一些受刺激的受体被保留下来，形成对过去感染的记忆，从而对未来类似类型的感染做出快速反应。适应性免疫系统中这种亲和成熟的过程构成了机体一生中免疫细胞的达尔文式进化。相比之下，在一些细菌和古细菌中，免疫力是直接从与环境的相互作用中获得的，并可遗传给后代。这些细菌使用CRISPR-Cas机制从攻击噬菌体（攻击细菌的病毒）中获得特定的基因组序列，并使用这些序列来攻击未来的入侵者。在这两种情况下，病原体的快速周转以逃避适应性免疫反应，在分子水平上造成了一场进化军备竞赛。理解这些适应性免疫系统对共同进化病原体的复杂动态反应，只有通过理论和实验的联合努力才有可能。本次研讨会将重点讨论这方面的一些问题，包括：（一）免疫库“适应良好”意味着什么，（二）适应系统的实际动态如何达到这种适应良好的状态？（iii）适应系统如何应对不断变化的致病环境，以及（iv）病毒和免疫系统之间共同进化的分子特征是什么，我们如何从生物学数据中检测这些特征？本次研讨会将汇集这些领域的许多顶尖专家。