Studying RNA structure and function in gene regulation during development

What we do

Research in the Beaudoin lab stems from two captivating biological observations that appear unrelated at first sight. The first is the fascinating process by which two of the most specialized and highly differentiated animal cells, the sperm and the oocyte, come together and transition to a completely naïve state from which they differentiate to form all the different cell types and tissues required to create a brand-new animal. This a fundamental process of embryonic development is universal across the animal kingdom.

At a whole different scale, at the level of molecules, we find that transcripts of RNA coordinate the flow of information circulating within a cell. The central role of RNA in biology is enabled by a broad diversity of RNA functions. RNA acts as a template for the construction of proteins. RNA operates as a platform to bind various factors to regulate gene expression. RNA also constitutes the backbone of some of the most important machineries found within the cell, such as the ribosome, the telomerase enzyme, the RNAse P, tRNA, the splicosome, and many others. Consider now that RNA is a polymer of four simple monomers; it is striking how such complex functions can arise from simple rearrangements of four base components. One thing is often forgotten, though. It is impossible to dissociate RNA function from RNA structure. RNA structure provides a fundamental regulatory layer of RNA activities.

In the Beaudoin lab, we are inspired by these two phenomena of dynamic cellular transitions during development and the role of RNA structure in governing the flow of cellular information. We aim to characterize RNA structure and functions to better understand vertebrate development. To this end, our lab uses the zebrafish and human cell lines as model systems, and we integrate an array of approaches that includes RNA molecular biology, computational biology, high throughput sequencing, genome-engineering, genetics, and developmental biology.

Our model systems

The Beaudoin lab is fascinated by the biological process of two highly specialized cells, the sperm and the oocyte, coming together and transitioning to a fully-grown organism. Although we know many transcription factors, epigenetic modifications, and enhancer sequences that orchestrate these cellular transitions, we know comparatively little about RNA structure governs gene regulation and expression during development.

To characterize the regulatory role of RNA structures during vertebrate development, our lab uses two model systems. First and foremost, we the zebrafish as a vertebrate system that provides numerous advantages. The zebrafish shares 70% of its genes with human, and 85% of human genes involved in diseases have a zebrafish homologue. The zebrafish is an in vivo system with robust genome engineering, mutagenesis and large progeny facilitating genetic studies. The zebrafish embryo is transparent making it ideal for microscopy techniques, and it grows at an extremely fast rate with most major tissues forming within the first 24 hour post-fertilization. Unlike in mammals, the fish embryo develops outside the mother’s body making it amenable to biochemical approaches. Our group has developed rapid massive parallel reporter assays to survey molecular functions of RNA across the genome with unprecedented complexity (Beaudoin et al. 2018). We also know that post-transcriptional regulation tightly orchestrates the first steps of embryogenesis during a process called the maternal-to-zygotic transition. No wonder why we love our fish!

Watch the first 24 hours of Zebrafish development! Video adapted from Swinburne et al. 2015.

To complement the powerful zebrafish model, we will also leverage human stem cell lines to uncover and characterize conserved gene regulatory pathways important for human development and health. Here, our goal is to study the regulatory role of RNA structures in human embryonic stem cells and induced pluripotent stem cells during various differentiation pathways (e.g. neuronal differentiation). Much of this research will be facilitated by the genome editing and reprogramming resources at the UConn Stem Cell Core Facility.

The Beaudoin lab is interested in how RNA structure regulates neural differentiation.

The Beaudoin lab is interested in how RNA structure regulates neural differentiation.

If all this sounds exciting, visit our research page to learn more about the projects ongoing in the lab.

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