A matter of scale: Within-host and between-host processes driving coevolution with parasites

项目摘要 理解宿主-寄生虫协同进化本质上是一个多尺度的生物学问题。这是 因为宿主的免疫系统和挑战它们的寄生虫/病原体对 多个生物尺度。在分子尺度上，主体分子，如Major 组织相容性复合物和Toll样受体结合寄生虫配体，从而帮助宿主 检测体内的寄生虫。在细胞尺度上，这种检测激活增殖 以及改变效应子功能的分化。在生物体的尺度上，宿主要么生存， 死亡，清除或耐受感染，这取决于免疫反应的类型和程度 由感染引起的。在人口规模上，生存和繁殖（因此， 宿主的进化适应性（evolutionary fitness）取决于宿主对抗感染的程度，而宿主的进化适应性（evolutionary fitness）取决于宿主对抗感染的程度。 寄生虫的传播（以及进化适应性）在很大程度上取决于 寄生虫会逃避宿主的防御 研究宿主-寄生虫的共同进化是具有挑战性的，尤其是因为多种生物学特性， 游戏中的鳞片共同进化的发现需要免疫学家（他们主要关注 与流行病学家（主要关注 主机间/传输过程）。研究创新需要理论家（他们的 数学模型提出了主机内进程如何驱动主机间进程） 与实验者（其实验模型允许测试内部的 宿主和/或宿主间假说）。即将举行的雅克·莫诺会议- 将于2023年10月在法国罗斯科夫举行的寄生虫共同进化会议将促进这种交流。 这次会议--以及更广泛的共同进化发现--将从 在不同的科学家群体中交流思想、假设、方法和综合 反映了人类的多样性。我们建议有选择地资助学员的旅费和生活费 （博士后学者和研究生）代表的背景已经 历史上被边缘化。这一建议将促进他们参与一个特别 互动，富有成效，并在主机寄生虫共同进化生成国际会议。

Project Summary Understanding host-parasite coevolution is intrinsically a multi-scale biological problem. This is because host immune systems and the parasites/pathogens that challenge them operate on multiple biological scales. On the molecular scale, host molecules such as the Major Histocompatibility Complex and Toll Like Receptors bind parasite ligands and thereby aid host detection of parasites in the body. On the cellular scale, such detection activates proliferation and differentiation that alters effector function. On the organismal scale, hosts will either live or die, clear or tolerate infections, depending upon the type and magnitude of immune response induced by infection. And on the population scale, the survival and reproduction (and hence the evolutionary fitness) of hosts depend upon how well the host combats infection, while the transmission (and hence the evolutionary fitness) of parasites depends in large part upon how well the parasites evade host defenses. Studying host-parasite coevolution is challenging, not least because of the multiple biological scales at play. Coevolutionary discovery requires that immunologists (who focus mostly on within-host processes) connect and collaborate with epidemiologists (who focus mostly on between-host/transmission processes). Research innovation requires that theoreticians (whose mathematical models propose how within-host processes might drive between-host processes) connect and collaborate with experimentalists (whose experimental models allow tests of within- host and/or between-host hypotheses). The upcoming Jacques Monod Conference on host- parasite coevolution, to be held in Roscoff, France, in October 2023, will foster such exchanges. The conference – and coevolutionary discovery more generally – would benefit hugely from the exchange of ideas, hypotheses, methods, and synthesis amongst a diverse group of scientists reflecting human diversity. We propose to selectively support travel and subsistence of trainees (postdoctoral scholars and graduate students) representing backgrounds that have been historically marginalized. This proposal would foster their participation in an especially interactive, productive, and generative international conference in host-parasite coevolution.