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

题为“分子共同进化：病原体-免疫系统相互作用的教训”的研讨会将于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学家聚集在一起。免疫的适应性机制已经进化成灵活和多样化的反应，并抵消病原体的快速进化，以提高有机体的生存。该项目的参与者致力于这种免疫动力学研究的前沿。其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性方法。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使医学进步成为可能。该讲习班的参与者中有近一半是女性，这有助于增加妇女在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显着的机制，以适应多样化和不断变化的致病环境。在脊椎动物中，新的受体不断通过基因组重组产生，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，以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。适应性免疫系统中亲和力成熟的过程构成了发生在有机体生命周期中的免疫细胞的达尔文进化。相比之下，在一些细菌和古生菌中，免疫力是通过与环境的相互作用直接获得的，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，并使用这些序列来瞄准未来的入侵者。在这两种情况下，病原体为逃避适应性免疫反应而迅速更替，在分子水平上造成了一场进化军备竞赛。只有通过理论和实验的共同努力，才能了解这些适应性免疫系统对共同进化的病原体做出反应的复杂动态。本次研讨会将集中讨论这一界面上的一些问题，包括：(I)免疫系统“良好适应”意味着什么，(Ii)适应系统的实际动态如何才能达到如此良好的适应状态？(Iii)适应系统如何应对不断演变的致病环境，以及(Iv)病毒和免疫系统之间协同进化的分子特征是什么，以及我们如何从生物数据中检测到这些特征？这次研讨会将汇聚这些主题方面的许多顶尖专家。

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.