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

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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.