Thursday, April 11, 2013

A way to use a genetic off switch with uv light

 A team of scientists led byDr. Alex Deiters and Dr. Jeffery Yoderv did research to find a way to control a genetic off switch in a way to be activated by UV light.  They developed a way to turn genes off at a specific time and specific region of an organism.  Both doctors had seperate teams.  Dieter team came up with a way to synthesize morpholinos that would only bind with RNA molecules after brief exposure to UV light.  Yoderv's team tested the caged morpholinos confirming the morpholinos did not disrupt gene function.     They were successful in their research by caging morpholino and then using a uv light and by doing this they effectively controlled a genetic off switch. The article is interesting because who would ever think you can control a genetic off switch.  I have an article attached on how genetic switches work that goes along with this article. 

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  1. There are several methods for photo-caging Morpholinos. The first step in understanding these methods is to understand something about the structure and use of the Morpholino oligos themselves. The following citations can help with that.

    Here's a paper published just after Morpholino oligos became commercially available, describing what the oligos are and their mechanism of action. This was published before splice modification became a popular technique.
    Summerton J. Morpholino Antisense Oligomers: The Case for an RNase-H Independent Structural Type. Biochimica et Biophysica Acta 1999 1489: 141-158

    This more recent protocols paper covers both splice modification and translation blocking.
    Moulton JD, Yan YL. Using morpholinos to control gene expression. Curr Protoc Mol Biol. 2008 Jul;Chapter 26:Unit26.8.

  2. And now for the various kinds of photo-caged Morpholinos.

    Deiters A, Garner RA, Lusic H, Govan JM, Dush M, Nascone-Yoder NM, Yoder JA. Photocaged Morpholino Oligomers for the Light-Regulation of Gene Function in Zebrafish and Xenopus Embryos. J Am Chem Soc. 2010 Oct 20. [Epub ahead of print]

    Deiters A, Yoder JA. Conditional Transgene and Gene Targeting Methodologies in Zebrafish. Zebrafish. 2006, 3(4): 415-429.

    Ouyang X, Shestopalov IA, Sinha S, Zheng G, Pitt CL, Li WH, Olson AJ, Chen JK. Versatile Synthesis and Rational Design of Caged Morpholinos. J Am Chem Soc. 2009 Aug 26. [Epub ahead of print]

    Shestopalov IA, Pitt CL, Chen JK. Spatiotemporal resolution of the Ntla transcriptome in axial mesoderm development. Nat Chem Biol. 2012 Jan 29. doi: 10.1038/nchembio.772. [Epub ahead of print]

    Shestopalov IA, Sinha S, Chen JK. Light-controlled gene silencing in zebrafish embryos. Nat Chem Biol. 2007 Oct;3(10):650-1. Epub 2007 Aug 23.

    Shestopalov IA, Chen JK. Spatiotemporal control of embryonic gene expression using caged morpholinos. Methods Cell Biol. 2011;104:151-72.

    Yamazoe S, Shestopalov IA, Provost E, Leach SD, Chen JK. Cyclic Caged Morpholinos: Conformationally Gated Probes of Embryonic Gene Function. Angew Chem Int Ed Engl. 2012 Jun 11. doi: 10.1002/anie.201201690. [Epub ahead of print]

    Tomasini AJ, Schuler AD, Zebala JA, Mayer AN. Photomorphs: A novel light-activated reagent for controlling gene expression in zebrafish. Genesis. 2009 Jul 30. [Epub ahead of print]

    Tallafuss A, Gibson D, Morcos P, Li Y, Seredick S, Eisen J, Washbourne P. Turning gene function ON and OFF using sense and antisense photo-morpholinos in zebrafish. Development. 2012;139:1691-1699. doi:10.1242/dev.072702