Rotation projects 2012
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Lab meeting: Monday, 1 p.m. SHM I room 143. Please check with Antonio for possible changes in the lab meeting schedule. (Pizza available)


Rotations available: 1st, 2nd and 3rd


The main question we are trying to address in the lab is what are the gene regulatory interactions that turn a fertilized egg into a vertebrate embryo (see also our research page)


Introduction: Upon fertilization, all embryos are transcriptionaly silent. During the first hours, cellular functions are supported by the maternal mRNAs and proteins. After a few cell divisions, the genome gets activated, transcription of the first embryonic genes begins and the maternal mRNAs are degraded. To tease apart this process (i) we are trying to identify the first genes activated in the embryo and what maternal factors are responsible for their activation. These genes play fundamental role to initiate the cascade of embryonic development and are likely to have important roles in other contexts such as cellular reprogramming.  (ii) we have identified microRNAs as important regulators of early development and the degradation of the maternal legacy. MicroRNAs are small RNAs that regulate gene expression post-transcriptionally. About 4% of the vertebrate genes encode microRNAs however their functions are largely unknown. In our lab we combine genomics with zebrafish mutants in the microRNA pathway to investigate the role of these smallRNAs in development. Finally we are also studying the roles of miRNAs during organogenesis using single miRNA knock down, GFP transgenic lines and live imaging. We are currently analyzing the role of miRNAs during muscle and vasculature development.



Projects:


Identification of the signals that initiate embryonic development. This project aims to identify the regulatory motifs and proteins that drive early gene expression. We will label early trascripts in the embryo using modified nucleotides, pull them down and identify them using high throughput sequencing. Using chromatin IP and sequence analysis we will identify the regulatory elements of these early transcripts. Using computational approaches we will compare the enhancer/promoter sequences on these early transcripts to identify common regulatory motifs. Finally these regulatory motifs will be used in a yeast one hybrid screen to identify the activators of early embryonic development.


Analysis of novel small RNAs in Zebrafish development. Using high throughput sequencing of wild type and dicer mutant embryos we will analyze the small RNA profile with the aim to identify novel small regulatory RNAs and other non-coding RNAs


Role of miRNAs during angiogenesis (vasculature development) Angiogenesis is the process by which blood vessels form, playing an important role in development and cancer. We have identified a microRNAs that regulates angiogenesis during zebrafish development. Using live imaging and miRNA knock down we are investigating how miRNAs modulate the cross talk between different tissues to regulate blood vessel formation.


There are additional  ongoing projects in the lab, please contact Antonio if you are interested in hearing about them. Antonio.Giraldez@yale.edu


Recent papers from the lab:


Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish. Bazzini AA, Lee MT, Giraldez AJ. Science. 13 April 2012: 233-237. [PDF]

miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration. Staton AA, Knaut H and Giraldez AJ. Nature Genetics. 2011. Published online 23 January 2011. [PDF]

A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND, Wolfe SA, Giraldez AJ. Science. 2010 Jun 25;328(5986):1694-8. Epub 2010 May 6. [PDF] [Supp_Material]


Review articles:

MicroRNAs Sculpt Gene Expression in Embryonic Development: New Insights from Plants. Bazzini AA, Giraldez AJ. Dev Cell. 2011 Jan 18;20(1):3-4. [PDF]


microRNAs, the cell's Nepenthe: clearing the past during the maternal-to-zygotic transition and cellular reprogramming. Giraldez AJ. Curr Opin Genet Dev. 2010 Aug;20(4):369-75. Epub 2010 May 6. Review. [PDF]


MicroRNAs as genetic sculptors: fishing for clues. Takacs CM, Giraldez AJ. Semin Cell Dev Biol. 2010 Sep;21(7):760-7. Epub 2010 Feb 10. Review. [PDF]


MicroRNAs in Development and Disease Alison A Staton, Antonio J Giraldez. Encyclopedia of Life Sciences. ELS. Review. Published online: 15 July, 2008 [PDF]