Blog series organized by Eric Peterman, Michael Onken, Kristen Verhey, and Daniel M. Suter
Syd Sattler, PhD Candidate, University of Washington Genome Sciences Department
Briefly describe the model you use.
Our lab studies early embryogenesis in the African turquoise killifish (N. furzeri). The African turquoise killifish has adapted to an aquatic habitat which dries completely during the annual dry season. As a result, this species exhibits rapid development and can enter diapause, a suspended state of development, allowing it to survive harsh conditions. These attributes make annual killifish an excellent model for studying developmental biology, aging, resilience, and cell type evolution.
Can you give a quick overview of your work and why your model organism is best suited for this work?
My thesis work aims to address how gene modules, networks of co-expressed genes, are repurposed during evolution to produce novel cell fates, allowing animals to adapt to their dynamic environment. However, the paucity of well-studied model organisms has limited our understanding of the extent to which developmental gene module reuse occurs across vertebrates and how it shapes cell type evolution. To address this in my thesis work, I am investigating how cell lineages have deviated from other vertebrates in the annual turquoise killifish, an emerging model organism facing extreme environmental conditions. Specifically, I discovered a novel innate immune cell lineage that may have evolved in response to environmental stress. By comparing the gene modules driving the immune cell trajectories in killifish with those in canonical vertebrate models, I aim to uncover novel gene module use that may have been repurposed to support species-specific novel phenotypes.
Have you worked in other model systems before, and how does your current system compare to previous systems?
While killifish are the first animal model I have worked with, I previously used human iPSC-derived microglia and neurons as models for neurodevelopment and neurodegeneration. The simplicity of differentiating stem cells into a single cell type in a dish is undoubtedly useful and allowed for genome-wide CRISPR screening. However, I have since recognized the additional benefits of studying cell types in their in vivo environment. The additional context provided by the developing embryo makes functional studies more salient and provides a more comprehensive understanding of cellular interactions and developmental processes.
What are the best and most challenging parts of using your model?
Annual killifish offer many of the same benefits embraced by the zebrafish community. Adult killifish produce large clutches, their embryos possess optical transparency, and are readily amenable to genetic manipulation. However, a key distinguishing factor of killifish is their notably short lifespan. While zebrafish can live for 3 to 5 years and take several months to reach sexual maturity, killifish complete their entire lifecycle in a brisk 4 to 6 months, achieving sexual maturity within mere weeks. Their accelerated timeline has proven to be the best part and the most challenging part of using killifish as a research model. On the one hand, it greatly accelerates the process of generating transgenic lines. On the other hand, it necessitates careful planning and management to maintain multiple generations at once which is necessary for a continuous supply of fecund fish.
In your own words, can you describe the importance of using uncommon / non-model organisms in research?
While research using common model organisms has undoubtedly produced outstanding discoveries and novel technologies, these exact advancements have, for the first time, opened the door to expanding the repertoire of model organisms studied in research. Just last year, I was astonished to hear a talk where a graduate student had plucked an organism off a California beach, sequenced and annotated its genome, performed single-cell sequencing across various developmental stages, and identified genes underlying its unique metamorphosis. This study showcases the untapped potential and unique insights that non-model organisms can offer, highlighting the vast biological diversity that remains to be explored. In a sense, nature has already conducted many of the genetic, developmental, and evolutionary experiments we wish to perform. We now have the tools to expand research from the small handful of common model organisms to a broader swath of the tree of life, which I believe will lead to an equally broader swath of novel discoveries.
About the Author:
This post was collaboratively written by several ASCB staff members.
