SPUR 2022: Perturbation of mesoderm diversification during vertebrate development

Background

Embryos develop from a pool of equivalent “stem cells” into adults composed of thousands of different cell types organized into tissues and organs. What are the mechanisms that choreograph such a complex process, such that that majority of embryos develop correctly into healthy adults? How do these mechanisms go wrong in diseases? Over the past century, developmental geneticists have carefully studied these mechanisms one gene at a time, to understand their role in this larger process. Our lab is taking a different approach adapted from systems biology. We have developed CRISPR tools for large-scale perturbation of gene regulatory networks in embryos, and combined them with single-cell sequencing methods for sensitive and detailed descriptions of the consequences of each perturbation. Now that we have these tools in hand, we are focused on the network of genes that control mesoderm specification and diversification. Mesoderm is formed early in the embryo, and diversifies during development to generate muscles, skeletal tissue, and organs such as the kidney, ovary and testis in adults. While we can appreciate the importance of mesoderm, we have a poor understanding of the gene regulatory networks that underlie its formation and diversification.

Student Role

This summer, a SPUR student will be an integral part of our team that is implementing these technologies to understand mesoderm. The student will learn experimental and computational methods from our expert team. On the experimental side, this includes breeding zebrafish, our model organism of choice, and injecting their embryos, as well as CRISPR experimental design and embryo manipulation. On the computational side, the student will be generating sequencing data and using software packages to analyze these data to understand mesoderm gene expression in normal and CRISPR-perturbed embryos. The student will use these new skills to understand how an interconnected network of transcription factors controls mesoderm development. Together, this project will combine extensive learning and front-line experience in a supportive and fast-moving science environment.

Student Learning Outcomes & Benefits

Biology is rapidly transitioning into an interdisciplinary field of study which mixes experimental and computational approaches that pull from other fields for experience and inspiration. A rapidly growing sector of pharma, biotech and startups is desperate for students who are fluent in both “wet” and “dry” lab approaches. In addition, these skills are highly sought-after in PhD programs nationwide. This project will teach a variety of cutting-edge technologies, including CRISPR, sequencing, and computational analysis, to accelerate skill acquisition. Since the student will be an essential component of our team, if successful, this project is highly likely to result in peer-reviewed manuscripts with the student as a co-author. In the past, undergraduates in the Gagnon lab have been co-authors and even lead authors on papers, and many have continued on to medical or graduate school.

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James Gagnon
Assistant Professor

School of Biological Sciences
College of Science

Our team of postdocs, graduate students, and undergrads provides a friendly and intellectually stimulating community to support each other. We often work in teams. Undergraduates in the Gagnon lab are considered as peer scientists in the lab, and treated as intellectual equals whose ideas are valued and respected. The student will be part of a small group, currently one postdoctoral fellow, one graduate student, and one undergraduate, who is building out the technologies. Their goal is to optimize and implement these technologies. With that in mind, our small team, including the SPUR student, will meet every week throughout the summer, alongside regular 1-on-1 meetings with the professor, to discuss short-term and long-term goals, and career planning. The student will also attend and present in our weekly lab meetings and journal clubs, and will be encouraged to attend virtual or in-person scientific conferences.