<div dir="ltr">To paraphrase:<br><div><br>All your base pairs are belong to us.<br><br></div><div>--Max<br></div></div><div class="gmail_extra"><br><br><div class="gmail_quote">On Thu, Aug 22, 2013 at 12:04 PM, Anders Sandberg <span dir="ltr"><<a href="mailto:anders@aleph.se" target="_blank">anders@aleph.se</a>></span> wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
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This is pretty nifty: optical control of gene expression and
epigenetics in nerve cells. Like optogenetics, but allowing primed
cells to be transformed by laser.<br>
<br>
<a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html" target="_blank">http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html</a><br>
Optical control of mammalian endogenous transcription and epigenetic
states<br>
<blockquote type="cite">The dynamic nature of gene expression
enables cellular programming, homeostasis and environmental
adaptation in living systems. Dissection of causal gene functions
in cellular and organismal processes therefore necessitates
approaches that enable spatially and temporally precise modulation
of gene expression. Recently, a variety of microbial and
plant-derived light-sensitive proteins have been engineered as
optogenetic actuators, enabling high-precision spatiotemporal
control of many cellular functions<sup><a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref1" title="Deisseroth, K. Optogenetics. Nature Methods 8, 26-29
(2011)" target="_blank">1</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref2" title="Zhang, F. et al. The microbial opsin family of
optogenetic tools. Cell 147, 1446-1457 (2011)" target="_blank">2</a>,
<a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref3" title="Levskaya, A., Weiner, O. D., Lim, W. A. & Voigt, C.
A. Spatiotemporal control of cell signalling using a
light-switchable protein interaction. Nature 461, 997-1001
(2009)" target="_blank">3</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref4" title="Yazawa, M., Sadaghiani, A. M., Hsueh, B. &
Dolmetsch, R. E. Induction of protein-protein interactions in
live cells using light. Nature Biotechnol. 27, 941-945 (2009)" target="_blank">4</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref5" title="Strickland, D. et al. TULIPs: tunable, light-controlled
interacting protein tags for cell biology. Nature Methods 9,
379-384 (2012)" target="_blank">5</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref6" title="Kennedy, M. J. et al. Rapid blue-light-mediated
induction of protein interactions in living cells. Nature
Methods 7, 973-975 (2010)" target="_blank">6</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref7" title="Shimizu-Sato, S., Huq, E., Tepperman, J. M. &
Quail, P. H. A light-switchable gene promoter system. Nature
Biotechnol. 20, 1041-1044 (2002)" target="_blank">7</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref8" title="Ye, H., Daoud-El Baba, M., Peng, R. W. &
Fussenegger, M. A synthetic optogenetic transcription device
enhances blood-glucose homeostasis in mice. Science 332,
1565-1568 (2011)" target="_blank">8</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref9" title="Polstein, L. R. & Gersbach, C. A. Light-inducible
spatiotemporal control of gene activation by customizable zinc
finger transcription factors. J. Am. Chem. Soc. 134,
16480-16483 (2012)" target="_blank">9</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref10" title="Bugaj, L. J., Choksi, A. T., Mesuda, C. K., Kane, R. S.
& Schaffer, D. V. Optogenetic protein clustering and
signaling activation in mammalian cells. Nature Methods 10,
249-252 (2013)" target="_blank">10</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref11" title="Zhang, F. et al. Multimodal fast optical interrogation
of neural circuitry. Nature 446, 633-639 (2007)" target="_blank">11</a></sup>. However, versatile and robust
technologies that enable optical modulation of transcription in
the mammalian endogenous genome remain elusive. Here we describe
the development of light-inducible transcriptional effectors
(LITEs), an optogenetic two-hybrid system integrating the
customizable TALE DNA-binding domain<sup><a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref12" title="Boch, J. et al. Breaking the code of DNA binding
specificity of TAL-type III effectors. Science 326, 1509-1512
(2009)" target="_blank">12</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref13" title="Moscou, M. J. & Bogdanove, A. J. A simple cipher
governs DNA recognition by TAL effectors. Science 326, 1501
(2009)" target="_blank">13</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref14" title="Zhang, F. et al. Efficient construction of
sequence-specific TAL effectors for modulating mammalian
transcription. Nature Biotechnol. 29, 149-153 (2011)" target="_blank">14</a></sup> with the light-sensitive
cryptochrome 2 protein and its interacting partner CIB1 from <i>Arabidopsis
thaliana</i>. LITEs do not require additional exogenous chemical
cofactors, are easily customized to target many endogenous genomic
loci, and can be activated within minutes with reversibility<sup><a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref6" title="Kennedy, M. J. et al. Rapid blue-light-mediated
induction of protein interactions in living cells. Nature
Methods 7, 973-975 (2010)" target="_blank">6</a>, <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref15" title="Liu, H. et al. Photoexcited CRY2 interacts with CIB1 to
regulate transcription and floral initiation in Arabidopsis.
Science 322, 1535-1539 (2008)" target="_blank">15</a></sup>.
LITEs can be packaged into viral vectors and genetically targeted
to probe specific cell populations. We have applied this system in
primary mouse neurons, as well as in the brain of freely behaving
mice <i>in vivo</i> to mediate reversible modulation of mammalian
endogenous gene expression as well as targeted epigenetic
chromatin modifications. The LITE system establishes a novel mode
of optogenetic control of endogenous cellular processes and
enables direct testing of the causal roles of genetic and
epigenetic regulation in normal biological processes and disease
states.</blockquote><span class="HOEnZb"><font color="#888888">
<br>
<pre cols="72">--
Anders Sandberg,
Future of Humanity Institute
Oxford Martin School
Faculty of Philosophy
Oxford University </pre>
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<br></blockquote></div><br><br clear="all"><br>-- <br><div>Max More, PhD</div><div>Strategic Philosopher</div><div>Co-editor, <i>The Transhumanist Reader</i></div><div><a href="http://www.amazon.com/Transhumanist-Reader-Contemporary-Technology-Philosophy/dp/1118334310/ref=sr_1_1?s=books&ie=UTF8&qid=1372225570&sr=1-1&keywords=the+transhumanist+reader" target="_blank">http://www.amazon.com/Transhumanist-Reader-Contemporary-Technology-Philosophy/dp/1118334310/ref=sr_1_1?s=books&ie=UTF8&qid=1372225570&sr=1-1&keywords=the+transhumanist+reader</a><br>
President & CEO, Alcor Life Extension Foundation</div>
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