The Giraldez Lab is part of the Yale Combined Program in the Biological and Biomedical Sciences (BBS). We are currently looking for graduate students. Interested students should read through the following rotation project descriptions and send Antonio an e-mail to arrange a meeting.
The main goal of the Giraldez Laboratory is to understand the cellular and molecular signals that initiate embryonic development to uncover universal principles that direct the development of a new life.
A universal step in all animals is the maternal to zygotic transition, whereby the transcriptionally silent egg activates the new zygotic program and removes the old maternal program. This central step in animal development can be considered the beginning of life from a transcriptional standpoint, whereby subsequent developmental decisions will depend on the correct activation of the zygotic program and regulation of the previous maternal program.
The questions: How the vertebrate embryo activate the silent zygotic genome? How does the embryo regulate the previous developmental program? How do the building blocks in the genome, coding and non-coding elements, orchestrate these processes?
The approaches: We have a multidisciplinary infrastructure (wet/dry) that allows us to combine genomics, embryology, biochemistry and computational biology to leverage the powerful genetics in zebrafish to understand vertebrate development.
Genome activation: We have recently identified nanog, oct4 and soxB1 as three factors required to activate the zygotic genome. In this project, we aim to gain mechanistic insights on how these factors establish a competent genome. We will use biochemical approaches (pull down and mass spectrometry) to identify the factors that are recruited by nanog, oct4 and soxB1, and genetic tools (crispr-cas9 loss of function, Chip-seq) to investigate their function in genome activation and development.
Translation regulation Using ribosome footprinting, we are for the first time able to study how translation is regulated genome wide. This computational project will investigate how translation efficiency changes across development, with the goal of defining co-regulated transcripts and identifying common sequence and structural elements that mediate regulation.
RNA structure in the transcriptome: Using high-throughput sequencing tools, we have developed methods to visualize the RNA structure in vivo. This project will investigate how the structure of the transcriptome changes across development and how it influences mRNA turn over and translation, with the goal of defining novel structural elements that regulate gene expression.
Micropeptides in development: Using ribosome foot printing, we have identified a large number of long-noncoding RNAs that encode micropeptides that are conserved and translated during embryogenesis. Using crispr/cas9 mediated mutagenesis and immunoprecipitation in vivo, we will investigate the function of these micropeptides in development, with the goal of identifying new signaling molecules.
Genetic screening: We are developing a genetic screen to define the factors that initiate vertebrate development. We have identified a set of chromatin remodelers, RNA binding proteins, transcription factors and genes of unknown function that are strongly translated in the early embryo. Using novel approaches developed in our lab, our goal is to identify their function in vivo.If you are interested in joining our lab or need more information, please feel free to send Antonio an e-mail to arrange a meeting.