Combining developmental biology and genomics to decode the mechanisms of gene regulation.
In the Giraldez Lab we study the regulatory code that governs gene expression. In the laboratory, we study this problem from four angles. First we look at how transcription is activated in the embryo during the maternal-to-zygotic transition. Next, we identify regulatory elements that drive post-transcriptional regulation of activated genes. Third, we pioneer molecular and computational methods to understand how these many elements are integrated to shape global gene expression. Finally, we study how mutations that disrupt this regulatory code cause human disease.
Using Zebrafish and Xenopus, we apply functional genomics to understand the post-transcriptional regulatory code in vertebrates. Our investigations span RNA stability (Giraldez, A et al. Science. 2006.), RNA modifications, RNA structure, RNA binding proteins and their recognition sequences, upstream ORFs, non-coding RNAs, and translation regulation (Bazzini, A et al. EMBO J. 2016.).
Post-transcriptional regulation is critically important in determining cellular phenotypes and behavior, particularly during early development when the genome is transcriptionally silent. We apply and pioneer novel high-throughput methods to elucidate regulatory networks at the system level. (Yartseva V⋆, Takacs C⋆, et al. Nat. Methods. 2016.)
We identified three key maternal transcription factors – Nanog, SoxB1 (Sox2) and Pou5f3 (Oct4) – as widespread regulators of gene activation during the maternal-to-zygotic transition in zebrafish (Lee M⋆, Bonneau A⋆, et al. Nature. 2013.). We now study the molecular mechanisms by which these factors direct activation and mediate genome competence during a fundamental transition in biology.
We use molecular models of Autism in zebrafish to understand the molecular, cellular and electrophysiological defects caused by ASD. We have recently described how CNTNAP2, a cell adhesion molecule and ASD-risk gene, leads to neurodevelopmental specification defects (Hoffman EJ, et al. Neuron. 2016.).