Antonio J. Giraldez PhD
Associate Professor of Genetics; Member of the Yale Cancer Center; Member of the Stem Cell Center; Director of Graduate Studies
Developmental Biology; Non-coding RNAs, Post-transcriptional regulation; microRNAs; Gene regulatory networks; Systems Biology; Zebrafish
Current ProjectsTwo main projects are currently ongoing: 1) We have identified a novel microRNA miR-430 that accelerates the deadenylation of maternal products during embryogenesis to facilitate gastrulation. Interestingly, misexpression of the human homologues (miR-372, miR-17-93) have oncogenic potential. Thus, identification of the in vivo miR-430 targets might provide a fundamental link between development and cancer. 2) MicroRNAs are expressed at the onset of differentiation and continue to be expressed through adulthood. We have observed that miRNAs accelerate target mRNA degradation. Thus, microRNAs targets can be identified by looking at mRNAs upregulated in the absence of the microRNA. We are using microarray analysis in dicer mutant embryos to identify tissue specific microRNA targets in neurons and muscle cells. Computational projects in the lab will analyze the regulatory motifs in microRNAs and 3’UTR elements of their targets to identify the gene networks controlled by microRNAs. Combining in vivo target identification with phenotypic characterization of dicer mutants will help us to understand the function of tissue specific microRNAs during cell fate specification and tissue homeostasis.
In our laboratory we use zebrafish as a model system to investigate the
role of microRNAs during vertebrate development. We combine genetics,
embryology, genomics, chemical and computational biology to address a
central question in biology: how does a fertilized egg develop into a
complex multicellular embryo. This process requires a precise spatial
and temporal regulation of gene expression. MicroRNAs are ~22nt RNA
molecules that repress gene expression post-transcriptionaly. More than
4% of the vertebrate genes encode microRNAs that are predicted to
regulate more than 25% of the protein coding genes. Thus, microRNAs
provide novel regulatory layer of unknown function with potential
widespread implications in development and disease. We have generated
zebrafish embryos mutant in the microRNA processing machinery (Dicer).
Dicer mutants lack all microRNAs and fail to undergo normal
gastrulation, brain and muscle morphogenesis.