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Antonio Giraldez |
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| Assistant Professor |
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* Assistant Professor
* B.S. University Autonoma of Madrid (Spain) 1998
* Ph.D. European Molecular Biology Laboratory, Heidelberg (Germany) 2002
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| Honors: | |
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* EMBO fellow 2002
* HFSP fellow 2003-2006
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| Research Interests | |
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* Zebrafish Development
* Post-transcriptional regulation by microRNAs
* Gene regulatory networks
* Systems Biology
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| Current Research: | |
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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.
Two 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.
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| Representative Publications: | |
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Choi WY, Giraldez AJ*, Schier AF*.
Target Protectors Reveal Dampening and Balancing of Nodal Agonist and
Antagonist by miR-430. Science. 2007 Aug 30
* Corresponding Author
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| Schier AF and Giraldez AJ. MicroRNA function and mechanism, insights from zebrafish. Cold Spring Harb Symp Quant Biol. 2006
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| Mishima Y#, Giraldez AJ#, Takeda Y, Fujiwara T, Sakamoto H, Schier AF, Inoue, K. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Current Biology, 2006 Nov 7;16(21):2135-42. # Equal contribution
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| Giraldez AJ, et al. Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006. Apr 7;312(5770):75-9.
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| Giraldez AJ, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005 May 6;308(5723):833-8.
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| Contact Information: | | |
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