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.
Our lab uses computational tools to model gene expression and translation. We are integrating data from multiple regulatory mechanisms that we have discovered in the lab, including microRNA regulation, RNA binding proteins activity, Translation, upstreamORF regulation, and codon mediated regulation.
Our research spans epigenetics, long non-coding RNAs, RNA-seq, structural RNA-seq, single-cell transcriptomics, ribosome profiling, iClip, gene networks and expression analysis
Several postdoctoral positions in computational biology are available for the following projects. Candidates would our team of four computational biologists in the lab working on the following projects:
The Giraldez laboratory provides an integrated environment for computational biologists and experimental biologists to develop these projects.
Applicants must have a strong background in bioinformatics, machine learning, sequence analysis, statistics and programming. Candidates will join a group of four computational biologists in the Giraldez laboratory.
Research Area: Epigenetics, Chromatin modifications, DNA methylation
Project title: Study of the epigenetic changes during the maternal to zygotic transition
Description of project: A postdoctoral position is available to identify the mechanisms that regulate gene expression during the maternal to zygotic transition, with a focus on epigenetic regulation. This project combines epigenetics, computational and developmental biology approaches.
Applicants must have a strong background in molecular biology and chromatin biology.
Research Area: The maternal to zygotic transition
Project title: Regulatory networks that control early embryonic development, maternal mRNA decay and zygotic genome activation
Description of project: A postdoctoral position is available to understand the regulatory interactions that control maternal mRNA decay and zygotic genome activation using CRISPR-Cas9 genetic screening
Applicants must have a strong background in genetics and developmental biology using a model system.
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.