Synthetic Biology
What might the quantity be, as related to synthetic biology? It could be the binding affinity of a protein to a DNA site.
synthetic biology International Meeting on Synthetic Biology, Hong Kong University
The term synthetic biology has long been used to describe an approach to biology that attempts to integrate (or "synthesize") different areas of research in order to create a more holistic understanding of life. More recently the term has been used in a different way, signaling a new area of research that combines science and engineering in order to design and build ("synthesize") novel biological functions and systems. The present article discusses the term in this latter meaning.
What is synthetic biology?
* Synthetic biology refers to both:
o the design and fabrication of biological components and systems that do not
already exist in the natural world
o the re-design and fabrication of existing biological systems.
What is the difference between synthetic biology and systems biology?
* Systems biology studies complex biological systems as integrated wholes, using
tools of modeling, simulation, and comparison to experiment. The focus tends to
be on natural systems, often with some (at least long term) medical
significance.
* Synthetic biology studies how to build artificial biological systems for
engineering applications, using many of the same tools and experimental
techniques. But the work is fundamentally an engineering application of
biological science, rather than an attempt to do more science. The focus is
often on ways of taking parts of natural biological systems, characterizing and
simplifying them, and using them as a component of a highly unnatural,
engineered, biological system.
Why bother?
* Biologists are interested in synthetic biology because it provides a
complementary perspective from which to consider, analyze, and ultimately
understand the living world. Being able to design and build a system is also one
very practical measure of understanding. Physicists, chemists and others are
interested in synthetic biology as an approach with which to probe the behavior
of molecules and their activity inside living cells. For example, differences
between how a synthetic system is designed to behave and how it actually behaves
can serve to highlight relevant intracellular physics. Engineers are interested
in synthetic biology because the living world provides a seemingly rich yet
largely unexplored medium for controlling and processing information, materials,
and energy. Learning how to effectively harness the power of the living world
will be a major engineering undertaking.
What is your approach towards synthetic biology?
* We are working to help create a general scientific and technical
infrastructure that supports the design and synthesis of biological systems.
Specifically we are working to (a) specify and populate a set of standard parts
that have well-defined performance characteristics and can be used (and re-used)
to build biological systems, (b) develop and incorporate design methods and
tools into a integrated engineering environment, (c) reverse engineer and
re-design pre-existing biological parts and devices in order to expand the set
of functions that we can access and program (d) reverse engineer and re-design a
'simple' natural bacterium.
Why are you working to redesign bacterium?
* Bacteria are the simplest known objects from the natural world that are
capable of replicating when provided with only simpler components (e.g., broth).
Still, bacteria are far from simple. Bacteria also provide the basic environment
in which synthetic biological systems exist and act (i.e., they are like the
power supply and chassis of a computer). By re-designing/recapturing a simple
living system we hope to learn how to better couple (and decouple) our designed
systems from their host environment.
Life isn't digital. Why are you trying to implement digital logic in cells?
* As engineers we are much better at thinking and designing digital systems. One
reason we are better at digital system design is that such systems create an
'abstraction barrier' between the detailed device physics level and the system
design and operation levels. The term synthetic biology has long been used to
describe an approach to biology that attempts to integrate (or "synthesize")
different areas of research in order to create a more holistic understanding of
life. More recently the term has been used in a different way, signaling a new
area of research that combines science and engineering in order to design and
build ("synthesize") novel biological functions and systems. The present article
discusses the term in this latter meaning.
Is what you're doing dangerous?
* Many technologies have the potential to be dangerous either through their
direct application or through society's (inappropriate) reliance on their
continued successful operation. Imaginable hazards associated with synthetic
biology include (a) the accidental release of an unintentionally harmful
organism or system, (b) the purposeful design and release of an intentionally
harmful organism or system, (c) a future over-reliance on our ability to design
and maintain engineered biological systems in an otherwise natural world. In
response to these concerns we are (a) working only with Biosafety Level 1
organisms and components in approved research facilities, (b) working to educate
and train a responsible generation of biological engineers and scientists, (c)
learning what is possible (at what cost) using simple test systems. All told, we
believe that the understanding and abilities to be gained from synthetic biology
justifies its responsible exploration and development.
* More recently, MIT, the J. Craig Venter Institute in Rockville, Md., and the
Center for Strategic and International Studies in Washington, D.C. have
announced a new study of the societal implications of synthetic genomics. Press
releases: MIT, SIS and Venter Institute. More information also available at
Synthetic Genomics Study.
What about ethical or moral issues?
* Do we inherit and passively pass along the living world or do we have a
responsibility to interact rationally with it? If we are going to interact with
the living world should we ground this interaction at a level of resolution
(i.e., molecular) that allows for the precise description of our actions and
their consequences? We don't presume to know all the answers to these questions
(and others) but we hope to participate in a thoughtful discussion of such
issues. The term synthetic biology has long been used to describe an approach to
biology that attempts to integrate (or "synthesize") different areas of research
in order to create a more holistic understanding of life. More recently the term
has been used in a different way, signaling a new area of research that combines
science and engineering in order to design and build ("synthesize") novel
biological functions and systems. The present article discusses the term in this
latter meaning.
What technologies would benefit synthetic biology?
* Fast and cheap DNA sequencing and synthesis would allow for rapid design,
fabrication, and testing of systems. Software tools that enable system design
and simulation are also needed. Still-better measurement technologies that allow
for observation of biological system state (i.e., the equivalent of a biological
debugger) are also needed.
What is the current commercial availability for de-novo gene synthesis? Has this
technology become competitive with standard gene cloning in terms of cost per
base and time?
* Current synthesis costs are about $1 per base pair. Current synthesis times
for a 1,500 bop gene are of order 4 weeks. So, we need a ~3-fold reduction in
cost and a ~10-fold reduction in turn-around time, from where we are today for
commercial DNA synthesis to be competitive with standard gene cloning. Such a
cost reduction could play out within the next two years; however, changes in
turn-around time are much harder to predict.
History
of the term
In 1974, the Polish geneticist Wallow Szybalski introduced the term "synthetic
biology"[1], writing: Let me now comment on the question "what next". Up to now
we are working on the descriptive phase of molecular biology. ... But the real
challenge will start when we enter the synthetic biology phase of research in
our field. We will then devise new control elements and add these new modules to
the existing genomes or build up wholly new genomes. This would be a field with
the unlimited expansion potential and hardly any limitations to building "new
better control circuits" and ..... finally other "synthetic" organisms, like a
"new better mouse". ... I am not concerned that we will run out exciting and
novel ideas, ... in the synthetic biology, in general. When in 1978 the Nobel
Prize in Physiology or Medicine was awarded to Arbor, Nathan's and Smith for the
discovery of restriction enzymes, Wallow Szybalski wrote in an editorial comment
in the journal Gene: The work on restriction nucleases not only permits us
easily to construct recombinant DNA molecules and to analyze individual genes,
but also has led us into the new era of synthetic biology where not only
existing genes are described and analyzed but also new gene arrangements can be
constructed and evaluated.
z Pages in category "Synthetic Biology"
Synthetic biology is a new and rapidly emerging discipline
that aims at the (re-)design and construction of (new) biological systems. Its
interdisciplinary nature between science and engineering, as well as the many
potential applications, amongst others, in the health, material, and energy
sectors, make it particularly exciting. The previous conferences SB1.0 and SB2.0
conveyed this spirit very well.
The third international conference of Synthetic Biology was held at the ETH
Zurich, Switzerland, from June 24-26 2007. We had a spectacular meeting with a
lot of cutting edge science and great workshops. You will find here more
information soon (proceedings, foots, videos). Earlier this month, students from
around the world locked horns in competition. Their challenge was to build
functioning devices out of biological parts. Erika Check finds out how they got
on.
Even if you're thinking big, you usually have to start small. Especially, as a
group of Swiss students found, when big means counting to infinity.
Thanks once more to all the partners, sponsors, helpers, and of course the
participants for making this a truly exciting meeting!!
Why Math in Synthetic Bio?
In the past 3 years, I've developed some very advanced methods for computing the
stochastic dynamical behavior of "small" physical or chemical systems, which
especially includes biological systems. The methods are an improvement over
existing ones, decreasing the amount of computational time by 1000x or more for
some systems, but still retaining accuracy. Now, I'm working on more methods to
better predict the long time behavior of biological systems.
But why is using math important in synthetic biology?
The idea is to develop an accurate model of a biological system (usually
focusing on a small subsystem of a single cell) and then predict what the
dynamics will be over time. If you can predict what the system will do before
you build it, you save yourself both time and money. The model should be a
"first principles" one based on the molecular interactions of each DNA site,
protein, RNA, etc molecule in the system. That way, if you know the interactions
of a DNA site in one model, then you should be able to put the same DNA site in
a different model and still predict what will happen. (No lumped interactions!)
Of course, we're still constrained by the limited amount of information we have
on molecular "parts". That's ok for now, because (one day) we should have that
information. Until then, we will need to be good engineers and make guesses
(yes, guesses) on what those interactions might be and how they affect the
system dynamics.
You would be surprised as to how much guessing goes into making 70 story
buildings, cars that move at 120mph, and lots of other contraptions that will
easily kill you if built incorrectly. The "engineer guess" is making sure that
if you're 500% wrong that nothing bad will ever happen. The technical term is
robustness. But, in practice, you assume the unknown quantity can take values
within a very large range and then you make sure that nothing breaks for any
value in that range. Of course, you have to pick which quantities to make your
design robust to. That's where you get this tradeoff between "robustness" and
"fragility". But End does teach an YAP. This year his class is devoted to
building counters - devices that count from, say, 1 to 32. That may not sound
like much of a challenge for students at the world's most prestigious
engineering school; in fact, it's the sort of thing a nerdy middle school kid
would solder together. But here's the rub: The counters his students design
won't be electronic, but biological. They won't be made of transistors, but DNA.
And they won't be inserted into breadboards, but living bacteria.
But we should be rigorous about our "guessing". We should be able to identify
_all_ possible behaviors that exist when varying the value of a specific
quantity. What might the quantity be, as related to synthetic biology? It could
be the binding affinity of a protein to a DNA site. It could be the enzymatic
Kat of a phosphorylation reaction. It could be the influx of a regulatory
protein from the extra cellular space. It is any parameter in our model that is
not entirely known.
The math behind computing _all_ possible behaviors of a system while varying one
or more parameters is called bifurcation analysis. The subject has always
interested me and it's actually extremely useful in real life. Computing that
your reactor has a sub critical Hop bifurcation at a critical parameter value
tells you that if your parameter is past this point, your reactor will suddenly
blow up and kill lots of people. Whoever said math wasn't useful? In practice,
they make sure the parameter never goes near that critical value. not even
remotely near it. So reactors generally don't blow up. Whew, that's good to
know. Synthetic biology aims to design and build new biological parts and
systems or to modify existing ones to carry out novel tasks. It is an emerging
research area, described by one researcher as “moving from reading the genetic
code to writing it.” Prospects include new therapeutics, environmental
biosensors and novel methods to produce food, drugs, chemicals or energy. This
POST note outlines recent developments, the possible applications and risks of
synthetic biology and examines policy options for the development and governance
of the research. students at MILT. are let off the leash to follow their
fancies. The annual month long Independent Activities Period is a playground for
the mind, offering courses, seminars, and special events devoted to everything
from energy-dispersive x-ray spectroscopy to poetry reading. There's
glassblowing, building spacecraft for mice, and the all-important
coolest-stuff-made-of-duct-tape competition. "I wish I didn't teach an YAP,"
says Drew End, an assistant professor in biological engineering. "I'd take a
whole bunch of the courses."
How is bifurcation analysis related to synthetic biology? Say you wanted to
create a gene therapy system that consisted of a biosensor + regulated
production of a therapeutic protein. There might be 120 parameters in your
system. You might have good information about 60 of those, so-so information
about 30, and the rest...who knows. But you want the gene therapy to work no
matter what. Even if you incorrectly measured the interaction between molecule A
and B. Even if you get a mutation that changes an interaction between molecule C
and D. It just has to work. If it doesn't, someone can die. So can you determine
the behavior of the model over all unknown parameters and make sure that the
system will never break? If the number of unknown parameters is 30, well ...
that's a 30 dimensional space to worry about. Mathematically, you could do
it...but it would take a while. Are there ways to speed up the process?
Absolutely. (I won't go into details here.) But my main point is that
bifurcation analysis is extremely important for designing synthetic biological
systems.
But, wait, I did say "stochastic dynamics" and the bifurcation analysis of
stochastic systems is ... not well developed yet. That's because when you're
working with probability distributions, the idea of a "qualitative change" in
the solution gets harder to define. And working with these types of systems is
harder in general. So that is what I am currently doing. And it is going well.
:)
The math can get very heady and I worry that people who lack the background will
become turned off by it. But the final product is very useful: You can find all
possible behaviors of a "small" physical or chemical system (such as biological
system) using a combination of existing and new simulation techniques. The words
"all possible" are extremely important. As it turns out, if your system has two
stable states, a "good" one and a "bad" one, then, because of the random nature
of the interactions, the dynamics might first go to the "good" state, but later
go to the "bad" one. Not good. But you can minimize the "escape" from the good
to bad state if you design the system well enough. This type of "escape" doesn't
happen if you describe the system using deterministic dynamics, but it happens
in real life. (One more reason why stochastic descriptions are important.)
If you've read this far, then my guess is that you're somewhat interested in
mathematics. Study it! (Especially non-linear dynamics, bifurcation analysis,
and stochastic processes.) They are useful for real life applications,
especially in new fields such as synthetic biology. If you're looking for a book
on non-linear dynamics I would suggest the one by Steven Stoats. The material is
at the intermediate-advanced undergraduate level with lots of pictures. IN 1965
few people outside Silicon Valley had heard of Gordon Moore. For that matter, no
one at all had heard of Silicon Valley. The name did not exist and the orchards
of Santa Clara county still brought forth apples, not Macintoshes. But Mr. Moore
could already discern the outlines. For 1965 was the year when he published the
paper that gave birth to his famous “law” that the power of computers, as
measured by the number of transistors that could be fitted on a silicon chip,
would double every 18 months or so.
Four decades later, equally few people have heard of Rob Carlson. Dr Carlson is
a researcher at the University of Washington, and some graphs of the growing
efficiency of DNA synthesis that he drew a few years ago look suspiciously like
the biological equivalent of Moore's law. By the end of the decade their
practical upshot will, if they continue to hold true, be the power to synthesize
a string of DNA the size of a human genome in a day
So to answer my initial question: "Why Math in Synthetic Biology?". Math is
needed because there's no way to build large, complex dynamical systems without
first understanding (and then predicting) what those dynamics will be. Math then
gives us the tools to guarantee certain types of behaviors even if we don't
exactly know all of the parameters of a model of the system. Also, using math
generates testable and precisely quantitative predictions about the biological
system of interest. Synthetic Biology is a new interdisciplinary Endeavour which
involves the recruitment of engineering principles to biology. Simple biological
elements can be adopted as reusable, components, which are well characterized
and can be used for the construction of more complex devices and systems. The
approach allows the biological application of engineering concepts such as
modularity, abstraction and insulation from underlying detail. The reuse of
modular components also facilitates software modeling, and work in the field is
promoting parallel developments in computer software. New students and workers
are coming into the field from very diverse areas, and need to come to grips
with the nitty-gritty of unfamiliar biological systems, engineering tools and
computer sciences. There is a demand for specialized coverage of this new field,
including educational and review materials. YET Synthetic Biology will aim to
support this growing new community.
The journal will publish conventional research papers in synthetic biology. It
will also provide a "nuts and bolts" view of this new field, and will provide
review and educational materials. In particular, we wish to support the
activities of young workers entering the synthetic biology field.
(This post is very hodgepodge and not very technical. For technical details on
the bifurcation analysis of stochastic systems, you'll just have to wait for the
paper. In the mean time, there's two papers on the stochastic numerical methods
that are 1000x+ faster than the original one. My group also published a paper on
the design principles behind an oscillating gene network. If you search Plumbed
for 'Sails H', they should come up.) While End is keen on counters at the moment
(they might have practical uses; for example, indicating how many times a given
cell has divided since the counter was last reset), they're just stepping-stones
to a new era in biology. Last year, his students programmed bacteria to form
polka-dotted colonies. The year before, they designed microorganisms that
blinked like Christmas lights. But the real purpose of the course isn't making a
particular biological circuit; it's figuring out what it takes to make any
biological circuit. The Second International Conference on Synthetic Biology
(SB2.0) took place on May 20-22, 2006, at the University of California,
Berkeley. The conference brought together a diverse group of participants from a
variety of disciplines, including some of the world’s leaders in biological
engineering, biochemistry, quantitative biology, biophysics, molecular and
cellular biology, bioethics, policy and governance, and the biotech industry. A
collaborative effort of Berkeley Lab, MIT, US Berkeley, and US, the conference
sought to promote and guide the further, constructive development of the field.
Mr. V8 202/3's progeny awards and honors:
1990 National Champion Get of Sire
1991 National Champion Get of Sire
1992 National Champion Get of Sire
1993 National Champion Get of Sire
1993 International Champion Get of Sire
1990 National Champion Female-Miss V8 725/3 "Amber"
1990 National Champion Bull-Mr.. V8 666/3
1991 International Champion Female-Miss V8 725/3 "Amber"
Seven Network and V8 Super cars Australia today confirmed the
signing of
a long-term partnership for broadcast television rights to the V8
Super car Championship Series.
Today's agreement sees Seven back in V8s - building on a rich history
and connection with the sport.
Seven's all-encompassing rights to V8s coverage will also see the
network return to Mount Panorama for coverage of the Super cheap Auto
Bathurst 1000 for the first time in a decade. Seven first broadcast the
Great Race 43 years ago and played a critical role in the iconic event's
rich history over more than three decades.
Seven invented the in-car camera technology that revolutionized
motor sports coverage and is recognized for innovation in its sports
television coverage. I went for a drive this afternoon I was driving for about
30min down port Wakefield road when I was stopped by a red light sitting there for
a little over 30sec a Holden commodore pull's almond side me and started to do a
burn out it went for around 40-45sec as tonight being a hot night I had my
windows open so all of the smoke fill's my car (it was that bad I didn't see the
light go green till the smoke had cleared). now I know this sounds like me just
winging but what if his car had started to go side ways in to my car or some
one that coo dent see throw the smoke just the green light went straight throw
and hit me from behind. well that's about it has anyone else had this happen to
them or something along thaws lines. Both the 2001 National Champion Brahman
Female and the 2002 International Champion Female are in the donor herd at
Double A Ranch, along with several other top females.