Genomics Pioneer: We Are a Software Driven Species, like all biology on the planet. If you change the software, you change the species.
This video is a bit funny on bunnies, but just check it out!
J.
Craig Venter, the first scientist to sequence the human genome,
describes the chemical and genetic basis of life as software. "Most
people view themselves as static entities, not billions of reactions
going on from constantly reading that software," he says.
"FANCY a liver that works a little harder? Synthetic
DNA circuits inserted into human stem cells could soon allow us to build
new organs with unprecedented precision and speed. The circuits can be
designed on a computer and assembled from ready-made parts ordered
online. The technique could prove an efficient way of making organs for
transplant without the worry of rejection, and raises the tantalising
possibility that it might one day be possible to upgrade the organs we
were born with. Human cells have already been used to create a tiny
liver and a set of neurons.
'At the moment, the aim is to normalise cells, but in future, enhancement has to be on the menu,' says
Chris Mason, a professor of regenerative medicine at University College London, who wasn't involved in the work.
'Everything we have in our bodies is hardwired,' says synthetic biologist
Patrick Guye
at the Massachusetts Institute of Technology, part of the team
pioneering the new approach. Apart from egg and sperm cells, all our
cells contain exactly the same genetic instructions. They develop into
different kinds of cell because
'epigenetic' switches turn some genes on
and others off.
By hijacking this mechanism, we can rewind adult cells
to an embryonic-like state and make them develop into different tissues.
To turn these induced pluripotent stem
(iPS) cells into a specific tissue type, they are typically placed in a
soup of DNA and signalling molecules. These enter the cells and flick
certain epigenetic switches. What gets turned on or off depends on the
ingredients in the soup. 'The problem is that there are tens of
thousands of these switches that all need to be set in the right way,'
says Mason. Another hurdle is that all cells in the soup are influenced
in the same way and grow into the same tissue type. But a piece of liver
tissue, say, is not the same as a functioning liver. The issue is even
more apparent with complex organs such as hearts, says Guye.
What would be more helpful is an
instruction manual that each individual stem cell can follow during its
development. And this is exactly what Guye's team has provided. They
started by looking at what happens in neurons and liver cells during
natural embryonic development – which genes are switched on and when.
They then designed and built artificial
DNA control circuits to reproduce this switching in iPS cells. The circuits are slotted together using a combination of
standard DNA parts – such as sequences that code for different proteins
– available from online repositories and newly synthesised genetic
material. These circuits were then chemically inserted into thousands of
iPS cells (
Nucleic Acids Research,
doi.org/m9d)."
Control from inside
"'You assemble it into one large logic circuit
and put it into the cell,' Guye says. 'It's interfacing with the
natural system. We're not replacing anything, we're putting a control
layer on top.'
Once in the cell, the circuitry kicks into
action. 'The idea is that the circuit is pretty much autonomous,' says
Guye. It can measure activity – such as levels of gene expression in the
cell – and react to it. When the circuit detects that an iPS cell has
turned into a precursor cell, for example, it can initiate the next
stage of development.
As yet unpublished results suggest that
the technique is faster and more reliable than existing methods of
creating tissues from iPS cells
(see Programming a new liver).
In one study, his team turned iPS cells into neurons in just four days
with almost 100 per cent success. 'If true, it's incredibly rapid,' says
Mason. 'Normally it takes weeks.'
Another advantage of Guye's approach is
that it only requires cells from one person. 'You get an organ that
really corresponds to an individual,' he says.
But before the technique can be used to
grow organs for transplant, Guye's team needs to find a way to get rid
of the artificial DNA once it has done its job. It currently lasts
inside the cells for a few weeks, and is passed on when they replicate –
it 'becomes physically part of the genome'. Although the artificial DNA
is unlikely to cause any harm, people will have legitimate concerns
about long-term implications, says Guye. One solution would be to build
circuits out of messenger RNA, which would survive long enough to push
the cells in one developmental direction and then degrade after a few
days.
'We are overriding the natural programming with our gene circuit,' says Guye, who presented the work at the
International Meeting on Synthetic Biology
at Imperial College London earlier this month. 'The cells already have
the knowledge. We are just helping them get on their way.' For many,
however, the ideal is to create tissues and organs with added extras
such as resistance to parasites (see '
Designer organs to order').
'This is what we are going to do,' says
Mason, although he admits we're not there yet and the regulators
certainly aren't. Takanori Takebe at Yokohama City University in Japan
agrees. 'I think it is theoretically possible to improve the functions
of generated organs,' says Takebe, whose group recently got
three cell types to self-assemble into a tiny liver similar to the one Guye has made. Ethical discussions will be needed though, he adds.
'At the moment, it exceeds our knowledge,'
says Guye. 'We would need to re-engineer much more than our gene
circuit.' But in the long term, he thinks the limitations will be
conceptual rather than technical. 'What type of new organ or function
would one wish for?'
'At the moment, the aim is to normalise cells, but in future,
enhancement has to be on the menu,' says Chris Mason, a professor of
regenerative medicine at University College London, who wasn't involved
in the work.
Oxford Journal Nucleic Acids Research - Rapid, modular and reliable construction of complex mammalian gene circuits
ABSTRACT Rapid, modular and reliable construction of complex mammalian gene circuits
We developed a framework for quick and reliable construction of complex
gene circuits for genetically engineering mammalian cells. Our
hierarchical framework is based on a novel nucleotide addressing system
for defining the position of each part in an overall circuit. With this
framework, we demonstrate construction of synthetic gene circuits of up
to 64 kb in size comprising 11 transcription units and 33 basic parts.
We show robust gene expression control of multiple transcription units
by small molecule inducers in human cells with transient transfection
and stable chromosomal integration of these circuits. This framework
enables development of complex gene circuits for engineering mammalian
cells with unprecedented speed, reliability and scalability and should
have broad applicability in a variety of areas including mammalian cell
fermentation, cell fate reprogramming and cell-based assays.
Organs enhanced with sensor or that release drugs on demand
In theory, he says, we can imagine creating a human organ for detecting
magnetic fields – birds have such things, for example. But
augmenting
organs, rather than making entirely new ones, is within closer reach.
Synthetic biology provides a rapidly increasing number of biological
sensors that react to different stimuli. These could be inserted into
tissues so that gene expression could be controlled by light alone, say,
which may allow less invasive treatments.
People with brain disorders like Parkinson's, caused by the loss of
nerve cells that produce dopamine, could benefit from neurons that
release an extra hit. Growing 1000 more-potent brain cells instead of
100,000 normal cells would make cell therapies more affordable and quick
to implement, says Chris Mason of University College London.
Other ideas suggested by researchers contacted by
New Scientist include
organs that can release drugs on demand, that are resistant to parasites
or that break down toxins we can't deal with."
Source:
"Super-organs: building body parts better than nature", 24 July 2013 by
Douglas Heaven, Magazine issue
2927.
http://www.newscientist.com/article/mg21929274.100-superorgans-building-body-parts-better-than-nature.html?full=true#.Uhhlmz8Xfcw
"Super-organs: building body parts better than nature. "
http://nextbigfuture.com/2013/08/super-organs-building-body-parts-better.html
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