[ExI] Fwd: [biomed] singularityhub: light-sensitive protein interaction used to control shape of mammalian cell

Bryan Bishop kanzure at gmail.com
Sun Dec 13 06:45:36 UTC 2009


Anselm was at H+ Summit and gave a great presentation:
http://adl.serveftp.org/~bryan/hplus-summit-2009/ansyem.html

Nice to see him showing up in Nature.

---------- Forwarded message ----------
From: Alejandro Dubrovsky <alito at organicrobot.com>
Date: 2009/12/13
Subject: [biomed] singularityhub: light-sensitive protein interaction
used to control shape of mammalian cell
To: biomed <biomed at postbiota.org>


(
http://www.nature.com/nature/journal/v461/n7266/full/nature08446.html
and
http://singularityhub.com/2009/12/11/light-used-to-remotely-control-mouse-cells-like-robots/
)

Nature 461, 997-1001 (15 October 2009) | doi:10.1038/nature08446;
Received 8 July 2009; Accepted 24 August 2009; Published online 13
September 2009

Spatiotemporal control of cell signalling using a light-switchable
protein interaction

Anselm Levskaya1,2,3, Orion D. Weiner1,4, Wendell A. Lim1,5 &
Christopher A. Voigt1,3

 1. The Cell Propulsion Lab, UCSF/UCB NIH Nanomedicine Development
Center,
 2. Graduate Program in Biophysics,
 3. Department of Pharmaceutical Chemistry,
 4. Cardiovascular Research Institute,
 5. Howard Hughes Medical Institute and Department of Cellular and
Molecular Pharmacology, University of California, San Francisco,
California 94158-2517, USA

Correspondence to: Wendell A. Lim1,5 Correspondence and requests for
materials should be addressed to W.A.L. (Email: lim at cmp.ucsf.edu).

Top of page
Abstract

Genetically encodable optical reporters, such as green fluorescent
protein, have revolutionized the observation and measurement of cellular
states. However, the inverse challenge of using light to control
precisely cellular behaviour has only recently begun to be addressed;
semi-synthetic chromophore-tethered receptors1 and naturally occurring
channel rhodopsins have been used to perturb directly neuronal
networks2, 3. The difficulty of engineering light-sensitive proteins
remains a significant impediment to the optical control of most
cell-biological processes. Here we demonstrate the use of a new
genetically encoded light-control system based on an optimized,
reversible protein–protein interaction from the phytochrome signalling
network of Arabidopsis thaliana. Because protein–protein interactions
are one of the most general currencies of cellular information, this
system can, in principle, be generically used to control diverse
functions. Here we show that this system can be used to translocate
target proteins precisely and reversibly to the membrane with micrometre
spatial resolution and at the second timescale. We show that light-gated
translocation of the upstream activators of Rho-family GTPases, which
control the actin cytoskeleton, can be used to precisely reshape and
direct the cell morphology of mammalian cells. The light-gated protein–
protein interaction that has been optimized here should be useful for
the design of diverse light-programmable reagents, potentially enabling
a new generation of perturbative, quantitative experiments in cell
biology.

----

Light Used to Remotely Control Mouse Cells Like Robots
No Comments
December 11th, 2009 by Aaron Saenz
 Filed under nanotechnology.

Plants use light to tell them where to move and how to grow. What if
animal cells could be directed in the same way? Now they can.
Researchers at the University of California San Francisco have modified
mouse cells with plant proteins so that they will change shape and move
in response to signals of light. As described in the recent publication
in Nature, Scientists were able to get the mammalian cells to follow a
weak red light and pull away from infrared light. Similar techniques can
be used to control other cell functions besides shape and movement. One
day, researchers hope, such modifications could be performed on human
cells to help direct the repair of spinal injuries and allow cells to
reconnect across gaps.

UCSF scientists placed plant proteins in this mouse cell so that it
would respond to light by moving and changing shape.

UCSF scientists placed plant proteins in this mouse cell so that it
would respond to light by moving and changing shape. The cell expanded
to follow the movement of a red light (circle).

While similar work has been performed in yeast and bacteria, this
experiment marks the first time that mammal cells have been upgraded in
this fashion. I’m impressed by the way that researchers got cells to
move like miniature remote control robots, but there are greater
implications. By inserting key plant proteins (called phytochromes) into
mammal cells, researchers have created a light-based switch that they
can insert into many different chemical pathways. The UCSF team focused
on the pathways which affect the cytoskeleton, but they could have
targeted protein interactions that control how food is processed, or
functions that impact cell life span. Imagine using specially tuned
light signals to keep some cells (say those with cancer) from processing
nutrients, or encourage other cells (say those in an area with nerve
damage) to repair and reproduce themselves. With the protein-based light
switch, scientists could change a cell’s chemical functions temporarily,
and repeat the process as needed later. That’s an amazingly powerful
tool.

When manipulating the mouse cells, researchers used combinations of red
light and infrared light. These types of light directly affect the plant
phytochromes that were inserted into the mammal cells. Basically, one
type of light will induce one kind of chemical reaction, while the other
light will stop or reverse that reaction. By bathing the mouse cell in
IR and providing a single spot of red light, the researchers were able
to get the cell to deform and follow the red spot as it moved over time.

While it took many minutes for the cell to move as the researchers
desired, the chemical reactions that the light was causing happened much
quicker. The UCSF team was able to control the position of these
reactions down to the micron level, and with a response time around one
second. This precision could have important implications if surgeons one
day used this sort of technique to repair damage in the body. It could
also facilitate fine control of the functions of the cell if and when
researchers try to control chemical pathways unrelated to cell movement.

I’ve always been impressed with how many technological advancements in
biology can be traced to a scientist taking the parts of one living
thing and sticking them inside of another. Putting plant proteins in
mammal (or some day, human) cells gives us the means to interact with
those cells via light. But why stop there? We could have skin cells that
produce chameleon pigments or blood cells with the antifreeze from Artic
bacteria. Most of this research would seem to be leading towards very
controlled forms of transhumanism. Humans have always shaped their
bodies to match their needs, but with tools like these we may gain
access to changes that are both profound and reversible.

[image credit: Wendell Lim et al, Nature]

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