Automated aquatic husbandry equipment to enable rigorous and reproducible axolotl studies - PROJECT SUMMARY: Axolotl salamanders are model organisms offering researchers unique opportunities to explore fundamental mechanisms underlying a variety of biomedically-relevant phenomenon. The Harvard Axolotl Facility (HAF) houses one of the most robust research colonies of axolotls in the U.S. This is a shared-use facility overseen by Dr. Jessica Whited. This proposal requests support to modernize the HAF, increasing its efficiency and capabilities by the addition of three double-sided flow-through racks for axolotl aquaria featuring real-time water quality measuring and adjusting functions. Axolotls have limbs which are anatomically and functionally similar to human limbs, yet axolotls can completely regenerate limbs throughout life. Elucidating how axolotls regenerate limbs will provide critical clues for scientific efforts aimed at therapeutic limb regeneration in human patients in the future. The precise genes whose activity enables limb regeneration can now be defined with the advent of appropriate experimental tools and genomic resources in axolotls. On the Harvard campus, axolotls are being used collaboratively to address fundamental questions such as: potential metabolic trade-offs associated with appendage regeneration (Dr. George Lauder); connections between regeneration and cancer (Dr. Brian Haas); how stress pathways intersect with stem cell activation following amputation (Dr. Isaac Chiu), and central nervous system regulate— or respond to—limb regeneration (Dr. Jia Liu). Our use of axolotls goes beyond limb regeneration. Researchers are using HAF’s axolotls to study the evolution of novel sensory traits (Dr. Nicholas Bellono), evolutionary aspects of pain sensation (Dr. Will Renthal), and evolution of skeletal morphologies such as pelvis (Dr. Stephanie Pierce). Thus, the HAF is truly a multi-use facility that has supplied a variety of labs with high- quality research organisms for study. Axolotls are permanently aquatic, and they are also cannibalistic. To generate and grow axolotls to appropriate sizes for experiments, they must be bred in-house and raised in separate enclosures, ensuring they are completely naïve to injury at the onset of studies. We are also generating targeted alleles of axolotls and transgenics. These animals must be raised to adulthood to establish lines, yet the axolotl generation time is one year. Thus, there is significant need for axolotl housing in the facility that is standardized and robust in the face of environmental fluctuations. Automation is key to the management of a modern axolotl facility, yet equipment for automation can be expensive and difficult to fund from traditional sources. Equipment requested will provide hundreds of individual enclosures for live axolotls to live with minimal environmental fluctuation and minimal human caretaker intervention, thereby simultaneously improving rigor and reproducibility while also improving efficiency. Together, these improvements will greatly enhance the rigor, reproducibility, and efficiency of research programs on campus using the axolotl model system.
