To acquire an understanding of the fundamental concepts of genomics and biotechnology, and their implications for human biology, evolution, medicine, social policy and individual life path choices in the 21st century.
Synthetic Biology
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Из курса от партнера University of Maryland, College Park
Genes and the Human Condition (From Behavior to Biotechnology)
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University of Maryland, College Park
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The Future is Now
Module Six discusses the history of biotechnology, its role in our lives today, and its prospects for the future.
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Raymond J. St. LegerProfessor
Department of Entomology
Tammatha O'BrienLecturer
Department of Entomology
[MUSIC]
Welcome back.
Synthetic biology has been a recognized field for
about ten years and acquiring the skills to
develop a terminator circuit that can kill cancer
cells doesn't seem like bad progress to me.
Nevertheless, some of the fanfare and hype that
surrounded synthetic biology five years ago is gone.
And there's a simple reason for this. The tools outpaced our knowledge.
The cost of genetic sequencing and synthesis
continues to plunge but the functions of
many genes in even the simplest forms
of life like bacteria and yeast remain elusive.
Genetic networks interact in complex, mysterious ways.
So the engineered parts do unexpected things when inserted into genomes.
That's because cells are machines whose complexity is many
orders of magnitude greater than a man-made engine or computer.
We sometimes call the unpredictable variation that results from the complexity
of life, noise.
Noise is a combination of all the things we can't quite account for.
Things like natural variation and the behaviours of genes
or proteins or molecular interactions, that haven't yet been described.
Synthetic biologists make confronting noise and scrutinizing it, thus
leading to a lot of new knowledge on cell biology.
That they should find them.
Quote, that to understand something you must first be
able to build it, is big in synthetic biology circles.
Well now that we understand cell biology when we can build a cell from scratch.
But then you still have the evolution elbowing its way in.
The DNA you put into your cells will mutate.
And these mutations will be selected for or against.
And if they are selected for, then they will
accumulate in your genetic circuits, and they'll change their function.
Evolution is a phenomenon which would drive any electrical engineer mad.
Well,
despite all that, the field is moving in a positive direction.
It's just that the road is far longer than some imagined.
And this isn't surprising.
Gartner, an information technology research and advisory firm, has coined
the term, hype cycle, to describe exactly this sort of phenomenon.
And the technology is introduced with enthusiasm, only to follow, be followed
by an emotional low when it fails immediately to live up to
its promise.
But Gartner also discovered that the cycle doesn't typically
end in what the firm calls the trough of disillusionment.
Rising form the ashes is the slope of enlightenment.
Many, that when viewed from a longer termed perspective the majority
of these much hyped ground breaking
developments eventually break much new ground.
And this is what is now happening in a lot
of new genetic areas like personalized medicine and synthetic biology.
So, for example, because DNA design, synthesis,
and assembly are now so much easier.
Many are talking about moving away from tweaking
existing genetic designs to construction of whole new organisms.
Species birthed entirely from our imaginations and
capable of feats impossible in the natural world.
You've probably heard of a certain scientist called Craig Venter.
Since the 1990s, Venter has wanted to
know what the minimum genome required for life would look like.
And what it would take to write a genome.
But back then DNA synthesis technology was too crude
and expensive for anyone to think about writing a genome.
While the recombinant DNA techniques used in
restriction enzymes and ligases to cut up
existing DNA and stitch it back together again, were to unwieldy for the task.
Huge advances in biotechnology mean that this work has moved from the molecular
to the digital. DNA is an information technology.
Genetic code, the written sequence of A's and T's and
C's and G's is cut and pasted on the computer.
DNA bases and sequences can be swapped in an outward position.
And then when the code looks right simply hit send.
A dozen different commercial DNA print shops
can now turn the digital code into biology.
In 2010, Venter announced that he had
created the world's first synthetic life form, Synthia.
Synthia was a cell whose one million base pair genetic code.
Copied and modified from an existing bacterium, have been assembled
not by its parent, but by a computer in Venter's office.
Once the code was complete, it was emailed to
Blue Heron Biotechnology,a company with a lot of DNA synthesizers.
And that sequence, including literary quotations
and website addresses, was then jammed into
another similar cell which didn't have any DNA, and the whole thing booted up.
It did live and it hadn't lived before.
It metabolized, grew, and divided.
The image behind me shows a bunch of Synthia cells dividing.
Well, for their purposes, Venter and his team defined a
synthetic cell as one that operates off of a chemically
synthesized genome.
But it doesn't fall under the type
definition of synthetic biology according to purists.
because the organism was still mostly a copy of one
in nature, and to be a designer life form it
would need to have its genetic function changed in some
deliberate and more useful way than just having literary quotations.
What Venter and his team did was an exquisite piece of genetic synthesis.
Now Craig Venter is incredibly
good at generating headlines and PR.
He also gets a lot of stick for these two things.
But he, he's a revolutionary and
Synthia is a really important technical achievement.
It shows we're not just capable of stringing a
couple of genes together, but also manufacturing an entire genome.
Even if it's only the smallest bacteria one we know of,
it still shows just how good we are at synthesizing DNA.
And this is highly important.
The old era belonged to DNA sequencing region of strings
of A's and T's and G's and C's in DNA.
Writing DNA creates many more opportunities.
Synthia is just the beginning.
Teams world wide are commonly making 16 chromosomes to create a synthetic yeast.
Synthia is a bacterial cell, and therefore has no nucleus.
Like humans and plants, yeast is a new caveatic
organism that contains complex structures that store DNA within a nucleus.
Yeast was picked as it only has about 6,000 genes which
makes it small compared to other more complex organisms such as plants.
And following the Synthia model, hunks of DNA will be designed
by teams on computers which will then be synthesized by specialized companies.
The team will then assemble the pieces of DNA in
a sequential manner and insert them into a yeast cell for
stripping out its natural DNA.
Well, Venter's grand scheme for Synthia and the minimal genome project he's been
working on, is to create a living template on which you can add functions.
And that really is his emphatic biology product, project.
As Venter says, it's like creating a basic chassis for a
car, which is then then available to decorate with whatever you want.
Likewise once complete, new strains of synthetic yeast
could help make products such as vaccines, biofuels and chemicals.
So synthetic biology though is not
just about medical and pharmaceutical applications.
It goes a lot wider.
You can also think about it in the context of manufacturing.
As engineers synthetic biologists look on biology not
just as a science, but as a manufacturing partner.
And what Venter is really interested in dealing with is energy production and
environmental issues.
Venter is interested in generating custom bacteria, designer bacteria
that will be provided with the genes to generate.
Fuel, plastics, clean up toxic waste or provide food.
The appeal of these designer bacteria is many fold.
They will reproduce themselves, and thereby generate
not only their product, but more biological factories.
And, and designer bacteria could produce
the same products as an industrial plant while feeding on pollution or sunlight.
Photosynthesis is powered up by 90
terawatts of energy, all across the, planet.
We can't use all that energy very well
right now, but we can imagine re-partnering with
biology, to make the things we need, without
putting such an environmental load on the planet.
So Venter and his group aspired to replace
the petro-chemical industry with strains of algae secreting
high yields of fuel.
They also think agriculture as we know it needs to disappear.
If strains of algae could secrete high yields of protein using less land and
water than traditional crops, it could represent
the best hope of feeding a booming planet.
Well to some extent, of course this kind of engineering
is already happening, all be it with less ambitious aims.
As I mentioned, it's now routine to use microbes make medicines.
The DuPont engineers are using modified bacteria to produce polyester for carpet.
Now it's been achieved already to show that we only grazing the surface
I already mentioned the engineered genes
that produces the anti malarial drug Artemisinin.
Jay Keasling and his team stitched together ten synthetic genes
derived from three different organisms to create this yeast strain.
Well of course, to create a flexible set of designer life forms,
you need genes that can get the job, whatever it is, done.
In 2003, Venter sailed around the world in his boat in search of new
forms of microbial life with novel genes that might be useful in synthetic life.
And to date they've discovered about 60 million new genes
that include some that help organisms survive in polluted waters.
Or they
could be used to produce hydrogen or new antibiotics.
Very useful though this is as a means of asserting the Earth's
genetic diversity, this approach is no longer cutting edge for synthetic biology.
Even the common set of biofix may soon be redundant.
The Florida based Foundation for Applied Molecular Evolution has added two
bases, Z and P to DNA's traditional four. So augmenting the
old genetic alphabet allowing proteins to be made with
amino acids that don't yet occur in living things.
In future, designer organisms could contain genes made from scratch, making
completely new types of protein with functions never seen in nature.
Well this is going to require the ability to arrange nucleotides in
the order required to produce a protein to a precise prescription.
And thanks to supercomputers,
protein chemists are increasingly able to predict how a given gene will fold.
And hence predict how the protein will behave.
Well all this means that the ultimate
limits of synthetic biology are hard to discern.
That's probably true of most genomic-based fields of study.
Not only because of the new technologies.
But because there, there is this great movement emoting
the free exchange of ideas, the free movement of technology.
A democratization
of science built into genetics and its offshoots.
There is unprecedented freedom of
information of publication of genetic information.
In fact, when researchers publish their work today, they upload the genes
and the phenotypes and the genomes
and transcriptomic profiles online in large databases.
The transcriptome, by the way, is the set of
RNA molecules found in a specified population of cells.
It tells you which part of
the genome the DNA is actively expressing RNA.
Well these databases are available to researchers and the public for free.
The United States National Institute of
Health National Center for Biotechnology Information
curates websites like GenBank, which contains
gene information on humans and other organisms.
And the Gene Expression Omnibus, or GEO, which contains thousands
of transcriptomic data sets describing when and how your genes
turn on and off, as determined by levels messenger RNAs.
The Database of Genotypes and Phenotypes or dbGaP contains over 50,000 samples
from studies which try to connect people's genotypes with their observed phenotypes.
This data comes from experiments with
snips genotypes, transcriptomics and sequencing results.
They contain all of the demographic, clinical and exposure
information on the study participants.
European Bioinformatics Institute or EBI manages
similar tools and databases online as well.
Well these databases are an invaluable resource for GWAS studies.
Having all this information publicly available means that bright people all
around the world are able to rub shoulders and exchange ideas.
This massively accelerated progress led us into many new creative directions.
And that not had taken place if only small numbers of people had been involved.
As an example, the democratic process built
into the BioBricks ethos where everything is
freely available and open access, is allowing
a new generation to embrace this vision.
Since 2003, every year high school and college students compete
in an international genetically engineered machine competition known as iGEM.
Where they need to think of a problem
and design a broader solution using only BioBricks.
Here's the high school team from the 2012 high school competition.
Looked like they're having fun.
These teams have pushed not only technical challenges, but creative ones as well.
2011's European champions designed a system for preventing
soil erosion and the conversion of land into desert.
The teams come from diverse backgrounds, maths, engineering, even astrophysics.
So they're unfettered by the narrowly
defined science disciplines.
[SOUND]
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