(light electronic music starts)
- [Lydia] Welcome to the NEB podcast,
Lessons from Lab & Life.
I'm your host, Lydia Morrison.
And today I interview Claudia Vickers,
director of the Synthetic Biology Future Science Platform
at Australia's national research agency, CSIRO.
Professor Vickers' latest research focuses
on engineering plant pathways within microbes
to manufacture natural products.
Throughout the pandemic,
she is also focused on bringing
the synthetic biology community together
via an online seminar series.
Hi Claudia, thanks so much for joining me today.
- [Claudia] Hi, Lydia. Thanks for having me.
It's a pleasure to be here.
- [Lydia] So I was wondering if we could jump right in
and you could tell us about your role at CSIRO.
- [Claudia] Yeah, sure.
So why don't I start by telling you a bit
about what CSIRO is,
because I guess it's an Australian institution,
so maybe not everybody's heard about it before.
So we're Australia's national science agency.
We really have just the one large scale science agency.
We're about 5,500 people.
And we have about 57 sites spread across Australia
with three or four sites internationally,
including in the US.
We deliver about 4.5 billion dollars a year
to the Australian economy through science and technology.
So we're really industry facing,
rather than academic facing.
We are really big and diverse research organizations.
So we work on everything from synthetic biology,
where I am, to space science, and everything in between.
Nothing is sort of off the board for us.
And we really deliver to the needs of Australian industry.
So very innovation-orientated,
we're the largest patent holder in Australia,
and very partner-orientated.
So we've got about 2,500 partners,
but we also deliver into the secondary school
and primary school teaching systems,
and university systems by taking on PhD students
and undergrads for internships and postdoctoral studies.
And we reach about 150,000 school kids a year
through those programs as well.
So pretty diverse organization.
So, my role-
- [Lydia] That's amazing.
- [Claudia] Yeah, it is.
And it's really exciting
to be part of an organization that's so interdisciplinary
because you can really build science
at the nexus of those different disciplines.
And that's what synthetic biology is really about.
So my role is as director of a program
called A Future Science Platform in Synthetic Biology.
Future Science Platforms are Horizon Three sites.
So they're far from the pointy end of translation,
but they're new areas that Australia needs
to develop strategically,
and are considered to be important for our future,
our research future, and our industry facing development.
So the Future Science Platform in Synthetic Biology
is obviously about developing synthetic biology.
There are two key missions of that program.
One is to build a collaborative research capability
across the whole nation.
So not just inside CSIRO,
but with university and research institute partners as well.
And the second one is to build
a synthetic biology-enabled industry in the country.
And so they're quite large, lofty objectives, of course.
We've been going now for about four years.
We're about a $60 million program.
We have about 250 people involved in the program.
We've trained about 90 early- to mid-career researchers,
from PhD level all the way through to
a young scientist's level, mid-career level.
We have about a hundred projects at any one time going
through the program and we're highly collaborative.
So we have about 45 partners nationally, internationally -
very well, internationally networked.
We've established really important infrastructure.
So a high throughput DNA and organism engineering facility
called the BioFoundry,
which I can tell you about if you're interested later on.
And we've done a lot of workshops,
training programs, and education programs.
We do a lot of policy input work.
So we feed into national and international policy
at various different levels.
And we work across both biophysical and social sciences.
So the program is really a melding
of biophysical and social sciences in that space.
It's a really exciting place to be in,
you know, it's a lot of fun.
So that's why it's important to me.
I think it's really critical in terms of
Australia's research capability internationally
and our ability to really drive impact.
- [Lydia] Absolutely.
So, was the past year of the pandemic particularly tough,
in terms of building
that Future of Synthetic Biology Program within Australia,
or what efforts have you been making
in the past year to sort of continue the drive forward?
- [Claudia] So in Australia,
I think in many ways we've been very fortunate
compared to the rest of the world
because we're an island nation
a long way from anywhere else.
Then it was relatively easy to close our borders
and go for an elimination strategy for coronavirus.
And we really have had very little impact
in terms of, you know, mortality.
We have had some long lockdowns that have been difficult,
but it hasn't cost us in terms of lives
where it has cost other people.
It's definitely cost livelihoods.
In terms of our research programs,
so we spent a lot of time reaching out
to find out what sort of support we could provide.
And often it was, you know,
no cost extensions to take into account
interrupted programs for our early mid career researchers
and such forth.
Some people have been out of the lab.
Most people were able to manage their projects
so that they could still be productive
during that time when they were out of the lab.
And then once we come out of lockdown.
So for us up here in Brisbane,
we had a few months of lockdown
and then went back to life
and we have snap lockdowns occasionally.
So I think, relative to the rest of the world,
you have many international friends
who've been literally out of the lab for a year.
We haven't had such a bad impact,
but we've been able to support our people
most of the time through those pandemic-inflicted delays.
- [Lydia] Absolutely.
And in order to continue to build a community
of synthetic biologists within Australia,
have you all been meeting online
during this time or have you been able to meet in person?
- [Claudia] Yeah, absolutely.
So we've started online seminar series,
which has been really fantastic.
And in fact, with an online seminar series,
you can reach a lot more people than you can reach
with a local seminar series.
So that's been wonderful
and I think it's given great opportunities to people.
We really have shifted online for almost everything.
So prior to pandemic,
I was probably traveling three to four months of the year
away from my home city,
and that was nationally and internationally.
And now I'm not traveling at all,
but I'm still doing almost everything
I would otherwise do,
apart from the in-person conferences.
So the online platforms are really good.
In Australia, it actually makes it very accessible
because a lot of the things that happen internationally
are more difficult to get to
because we're so far away from everything.
The only downside is that
a lot of it happens in the middle of the night.
So (chuckles) it can be a bit challenging
in terms of time zones.
- [Lydia] Absolutely, much like this interview. (chuckles)
I wanted to shift focus a little bit
and talk specifically about your research.
I read that your research focuses
on engineering plant pathways
within plants and microbes
in order to manufacture natural products.
Could you tell me more about that work?
- [Claudia] Yeah, sure.
So I'm a plant molecular biologist by training
and I spent probably a decade working on
engineering in plants and using my engineering skills
to better understand plant physiology and stress responses.
And during that time,
I was working in a class of natural products
called isoprenoids.
So these isoprenoids are really fascinating,
and they're a really large family of natural products,
and they include small volatile molecules
and long complex molecules that are heavily decorated.
And they have roles in membrane stabilization
and volatile messaging between plants,
and between plants and insects.
They attract insect pollinators.
Many of the colors and the flavors
that come from the food that we eat,
come from the isoprenoids
and isoprenoid molecules in them.
So carotenoids - your reds and your yellows and oranges.
So these are all in the isoprenoid family.
And I was interested in those
because there's a molecule called isoprene,
which is a five-carbon hydrocarbon.
It's very small, it's volatile, and it's emitted by plants.
And it's emitted in teragram amounts per annum
into the atmosphere from the biota.
And the question is, you know,
this is an enormous amount of carbon
going into the atmosphere and it's-
So isoprene isn't a greenhouse gas per say,
but it interacts with other gases in the atmosphere
that would otherwise soak up greenhouse gases
and increases the resident time of greenhouse gases.
So it's really important in global atmospheric value
with geochemical cycles,
but we didn't really understand properly
why plants made that molecule.
So I was interested in understanding better
the physiology around that.
And then it turns out that they-
That it's basically part of their stress response system.
It interacts with their antioxidant metabolism
and helps them deal with oxidative stresses.
So that was the piece of work that I was doing
to learn about isoprenoids and start working in that space.
And then when I came back to Australia,
I became interested in this metabolic engineering thing.
And metabolic engineering is essentially redesigning,
in this case, microbes and their metabolism,
to channel carbon from the feedstuff that you give to them
all the way through to the product
that you're interested in making,
that has an industrial application.
And it turns out that isoprenoids have
many, many different industrial applications.
They're such a large and chemically complex
and diverse group of natural products
that they have many different applications.
So they range from pharmaceuticals
to flavors and fragrances,
food additives, colorants, cosmetic ingredients, solvents,
monomers that can be made into polymers
to make rubbers and fibers,
and all the way up to very high volume, low value products,
like biofuels.
So we have a whole range of things that we can make.
- [Lydia] That's amazing.
So what is the success been like in having-
in reprogramming microbes to produce these?
- [Claudia] Yeah, so we've done quite a lot of work on this.
There are two different pathways
that are involved in producing these.
In yeast, the mevalonate pathway,
which is a pathway that's found in us as well.
So it's quite interesting to study
from a physiological point of view
and for a lot of different applications.
So what we have found is
that isoprenoids exist in different classes
that are related to the number of carbon molecules
in their isoprenoid tail.
And some of them are really challenging to get to.
And so we've had to develop mechanisms to bypass
or redirect carbon at specific nodes
in the isoprenoid pathway.
So we can make either five carbon
or 10 carbon, or 15 carbon compounds.
And we found that using protein degradation
as a metabolic engineering tool,
instead of trying to up-regulate or down-regulate
at the transcriptional level,
was really successful.
Particularly when you're dealing with a protein
that is essential,
so you can't just knock it out,
or that's very stable.
So transcription lockdown isn't very effective.
So that's a tool that we've used
to really successfully redirect metabolic flux
to various nodes in the isoprenoid pathway.
And that's delivered gram per liter titers,
tens of grams per liter of the products
that we're interested in,
which is essentially an industrial level
from a mid-level chemical, so a solvent or a polymer.
And we're really excited by that
because that's real world impact.
- [Lydia] Absolutely.
And so you mentioned that
you can produce five carbon, 10 carbon, 15 carbon.
Is there a reason that you're producing
these multiples of fives?
- [Claudia] Really good question.
It's called the Isoprene Rule,
and I'm not going to try and pronounce the name of the guy-
(chuckles) I think it's Ruzicka.
He came up with the Isoprene Rule.
So the reason is because
at the bottom end of the metabolic pathway
that makes isoprenoids,
the mevalonate pathway or the other pathway,
it makes five-carbon parental phosphates,
called isopentenyl pyrophosphate
and dimethylallyl pyrophosphate, and they're isomers.
And if they're five carbon units
and you use them just like Lego building blocks,
which is a beautiful analogy
for the way synthetic biology works,
to add one unit and another unit and another unit.
And that's why you have five, 10, 15, 20 carbon, et cetera,
modular isoprenoid compounds.
There are others that, you know,
you can take individual carbons away
and get different carbon numbers,
but that's the basic background
of why they are modular like that.
- [Lydia] That's interesting.
I love the simplicity in nature that turns up
in even the most complex scientific processes (chuckles).
- [Claudia] Yeah, it is.
And it's actually, I think, unusual nature.
So the basic tenet behind synthetic biology
is that we can treat biological systems
like almost like integrated circuits
and we can modularize the DNA-encoded componentry
and build it up into more and more complex systems.
And it works fine,
but of course, biology is mutable and it evolves.
So it's not quite as simple
as working with an electronic circuit board,
but it's really more about the philosophy that sits around
that using Design-Build-Test learning cycles
that are iterative,
by using high throughput engineering,
modularized engineering approaches,
and components that you can build up
in a more and more complex way.
- [Lydia] Yeah.
And I think what you're describing is really
the basis of synthetic biology, right?
- [Claudia] Yeah.
And that basically allows you to engineer the biology
in a more precise and sophisticated,
and much more rapid way
to get to a solution to whatever problem
you're trying to solve more quickly.
- [Lydia] I think it's a great application of,
sort of the theories of computer science
and electronic programming to biology.
And it's amazing how similar
the two systems can actually be.
- [Claudia] Yeah.
And the thing about this
is that it's truly interdisciplinary.
So it's blending of biological engineering
with automation and robotics,
and artificial intelligence to dealing with big data sets.
And to do that,
there's not that many places
that allow you to access all that capability under one roof.
And CSIRO is obviously ideal for that
because it's such a broad organization.
- [Lydia] Yeah.
Another example of how the integration
of multiple scientific disciplines,
but even beyond scientific disciplines,
into different areas of study in general
can really be beneficial
in terms of moving science and understanding forward.
- [Claudia] Yes, very much so.
- [Lydia] So where do you see
synthetic biology heading in the future?
- [Claudia] Well, I mean,
I think the cutting edge of synthetic biology now is...
That nexus of...
big data and artificial intelligence,
and bioengineering, of course.
And we're really just starting to explore into those spaces.
We haven't really cracked the question of
how do we get artificial intelligence algorithms
to suggest the next step,
as opposed to just deal with
and assess all the data and information.
So how do we feed it into
that Design-Build-Test learning cycle?
So that's one of the areas
that we're working in at the moment.
And in terms of, you know,
where are the next Horizon Three science questions,
exploring into that space,
I think is really very exciting.
- [Lydia] Yeah, absolutely.
Lastly, I was just wondering if you have any sort of stories
about something good or inspirational
that's happened in your life
or in your research since the pandemic began?
- [Claudia] Well, the immediate good thing is
not traveling so much.
(laughs)
For me, well, most of that might sound weird to some people.
For me, it's really great to be able to actually sit at home
and focus for long periods of time
without having to be up and off
and around the world and onto the next thing.
And it's been,
I've spent a lot more time with my family
on a day-to-day basis.
So I have two small kids,
they're nine and six,
and they miss me a lot when I'm traveling.
So it's a challenge always
to be in a position that's...
relatively senior
and involves a lot of travel away from home.
And when you're doing that with little children,
then that's a challenge as well,
but it's been a lot easier in that period of time
from that perspective.
So that's my good story.
- [Lydia] Yeah. I think that's wonderful.
And I think that that's probably
a lot of people's good stories.
You know, I think that,
I think that one of the lessons
that's come out of the pandemic
is that, you know,
we can collaborate globally and communicate.
We can do all that, you know,
from the comfort of our own home
with the technological advances
that we have available to us today.
And certainly some of those interactions
aren't exactly the same as they might be face-to-face.
But I think that,
I think that the pandemic has taught us
that we're actually capable of doing a lot more remotely
and still making important connections remotely,
where we used to feel like we needed
to be in person for those interactions.
- [Claudia] Yes. I think that going forward,
the global footprint,
carbon footprint of the scientific community
will probably decrease.
Nothing can replace those personal interactions,
but we can do a lot
and we can probably do those less frequently
and still get good value out of it.
- [Lydia] Absolutely.
Thank you so much for joining me today, Claudia.
- [Claudia] Thanks, Lydia. A pleasure.
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- [Lydia] Thanks for listening to this episode
of the NEB podcast.
Join us next time
when I interview plant geneticist Kate Creasey,
president and founder of the Grow More Foundation,
whose mission is to help end world hunger
by bringing synthetic biology tools to developing countries
and enabling communities to grow more fruitful crops.