Collaborative Research: Immune tradeoffs during tissue regeneration in mammals

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Why can salamanders re-grow amputated limbs but humans cannot? Understanding the mechanisms that favor tissue regeneration in lieu of tissue repair remains one of the great unanswered questions in biology. A particularly intriguing hypothesis, though poorly investigated, is that the loss of regenerative capacity in higher vertebrates coincides with the presence of a strong adaptive immune response. Now, the recent discovery of complete tissue regeneration in wild African spiny mice (Acomys) compared to the failure to regenerate in a co-occurring rodent (Myomyscus), allows a comprehensive examination of the links between immunity and regeneration in wild, pathogen-exposed, and fully immunocompetent adult mammals. Specifically, this study tests the hypothesis that tradeoffs in immunity along (1) innate vs. adaptive and (2) pro vs. anti-inflammatory axes underlie variation in the ability and rate of regeneration between these wild species. Quantifying immune and inflammatory changes at the cellular and molecular level in response to injury is expected to reveal a bias towards innate immunity and anti-inflammatory molecules in regenerators, and a shift towards adaptive immunity and pro-inflammatory responses in non-regenerators. Project results will provide fundamental insight into the mechanisms that constrain regenerative ability in mammals. Because regeneration biology is a fascinating topic with great potential to excite students about science, the investigators will engage U.S. and international students of all ages in the project. Graduate and undergraduate students from the U.S. will travel to Kenya, where animal work will take place, to actively participate in the study and collaborate with Kenyan students and scientists. The project team will also make a series of visits to a local Kenyan girls' secondary school and a primary school to showcase basic concepts in regeneration biology using African spiny mice as a tool. The international component of this study is co-supported by NSF's Office of International and Integrative Activities.