NSF Postdoctoral Fellowship in Biology FY 2021: Using butterfly wing color patterns to elucidate an uncharacterized Wnt pathway

这一行动资助了NSF 2021财年生物学博士后研究奖学金，扩大了生物学中代表性不足群体的参与。该研究金支持一项针对该研究员的研究和培训计划，该计划将增加生物学中代表性不足的群体的参与。多细胞动物共享共同的信号通路，这些信号通路负责从早期动物(胚胎)到成年动物的模式形成和调控发育。其中一个这样的途径被称为Wnt信号途径，它的研究有助于我们理解细胞与细胞之间的交流、动物发育、干细胞生物学和癌症。WNT途径已经得到了很好的研究，而“规范途径”是最好的理解。然而，Wnt途径也有非典范功能。这项研究旨在整合基因组工具和蝴蝶翅膀图案的属性，以确定Wnt信号如何指导这些翅膀的图案形成。此外，该研究员将利用蝴蝶生物学的自然吸引力，增加未被充分代表的群体在生命科学中的参与。具体地说，(1)为双语学校创建西班牙语主动学习模块，(2)每年向两名高中生提供暑期实习，由赞助科学家Arnaud Martin博士指导。(3)鼓励不同的科学家参与博士后水平。蝴蝶翅膀图案在视觉上引人注目，是分化细胞的二维阵列，其中来自组织的信号输出直接转化为颜色图案。来自该研究员的博士工作和赞助实验室的初步数据表明，保守的WntA分子组织了形成颜色的鳞状细胞的离散区域，可能独立于典型的Wnt途径。因此，这位研究员将产生一个缺乏WntA蛋白的朱尼亚蝴蝶的实验室群体；然后，她将调查WntA的存在/缺失对翅膀发育过程中基因表达和染色质可及性的影响。这些数据将提供全基因组范围的细胞对WntA信号反应的图景，该研究员将使用这些图景来选择特定分析的候选基因：可视化发育翅膀中的mRNA和蛋白质(即免疫化学)，以及CRISPR/Cas9基因敲除。这位研究员将正式测试WNTA信号的非正则性，并解决介导信号整合和导致尖锐的细胞规范结构域的分子机制，如在描绘颜色模式的尖锐边界中观察到的那样。这项原创性工作将对全面理解Wnt信号非常重要，并可能为可能延伸到整个动物王国的途径的新方面提供线索。在这份提案中，该研究员将与未来科学家的外联计划、培训和指导一起工作，并为拉丁美洲和对EvoDevo感兴趣的第一代研究生和博士后建立一个网络小组。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Broadening Participation of Groups Under-represented in Biology. The Fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. Multicellular animals share common signaling pathways that are responsible for patterning and regulating development in early animals (embryos) all the way to adults. One such pathway is called the Wnt signaling pathway, and its study has been instrumental to our understanding of cell-cell communication, animal development, stem cell biology, and cancer. Wnt pathways have been well studied, and a “canonical pathway” is the best understood. However, there are non-canonical functions of the Wnt pathway as well. This research aims to integrate genomic tools and the attributes of butterfly wing patterns to determine how Wnt signals instruct pattern formation in these wings. Furthermore, the fellow will take advantage of butterfly biology's natural appeal to increase the participation of underrepresented groups in life sciences. Specifically, (1) creating a Spanish-language active learning module for bilingual schools, (2) providing summer internships to two high-school students per year with the sponsoring scientist Dr. Arnaud Martin. (3) Encouraging the participation of diverse scientists at the postdoctoral level.Butterfly wing patterns are visually compelling, two-dimensional arrays of differentiated cells where signaling outputs from the tissue are directly translated into color patterns. Preliminary data from the fellow's Ph.D. work and the sponsoring lab proposes that the conserved WntA molecule organizes discrete domains of color-forming scale cells, potentially independently of the canonical Wnt pathway. Hence, the fellow will generate a laboratory colony of the butterfly Junonia coenia deficient for the WntA protein; then, she will survey how WntA presence/absence impacts gene expression and chromatin accessibility during wing development. Those data will provide a genome-wide landscape of the cellular responses to WntA signaling, which the fellow will use to select candidate genes for specific assays:visualizing mRNA and protein in the developing wings (i.e., immunochemistry), and CRISPR/cas9 gene knock-outs. The fellow will formally test the non-canonicity of WntA signaling and tackle the molecular mechanisms that mediate signal integration and result in sharp cell specification domains, as observed in the sharp boundaries that delineate color patterns. This original work will be important for a comprehensive understanding of Wnt signaling and may shed light on novel aspects of the pathway that could extend across the animal kingdom. In this proposal, the fellow will work with outreach programs, training and mentoring of future scientists, and develop a networking group for Latin-American and first-generation graduate students and postdocs interested in EvoDevo.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.