NEB Podcast #33 -
Transcript
Interviewers: Lydia Morrison, Marketing Communications Writer & Podcast Host, New England Biolabs, Inc.
Interviewees: Professor Claudia Vickers, Director, CSIRO Synthetic Biology Future Science Platform & Adjunct Professor, Queensland University of Technology and Griffith University
Lydia Morrison:
Welcome to the NEB Podcast, Lessons from Lab and 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 Vicker's latest research focuses on engineering plant pathways within microbes to manufacture natural products. Throughout the pandemic, she has also focused on bringing the synthetic biology community together via an online seminar series. Hi Claudia, thanks so much for joining me today.
Claudia Vickers:
Hi, Lydia. Thanks for having me. It's a pleasure to be here.
Lydia Morrison:
I was wondering if we could jump right in and you could tell us about your role at CSIRO.
Claudia Vickers:
Yeah. Sure. 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. 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 U.S. We deliver about four and a half billion dollars a year to the Australian economy through science and technology, so we're really industry facing rather than academic facing. We're 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 off the board for us. 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.
Claudia Vickers:
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 post-doctoral studies. We reached about 150,000 school kids a year through those programs as well. So pretty diverse organization. So my role-
Lydia Morrison:
That's amazing.
Claudia Vickers:
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, at the nexus of those different disciplines. And that's what synthetic biology is really about. So my role is as the director of a program called A Future Science Platform in Synthetic Biology. Future Science Platforms are Horizon Three, Five. They're far from the pointy end of translation, but they are 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.
Claudia Vickers:
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, 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. 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 level, mid-career level. We have about a hundred projects at any one time going through the program and we're highly collaborative. We have about 45 partners nationally, internationally, very well internationally networked.
Claudia Vickers:
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. We feed into national and international policy at various different levels. And we work across both biophysical and social sciences. 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. 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 Morrison:
Absolutely. 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 continue the drive forward?
Claudia Vickers:
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. It was relatively easy to close our borders and go for an elimination strategy for coronavirus. We really have had very little impact in terms of mortality. We have had some long lockdowns that have been difficult, but it hasn't cost us in terms of lives the way it has cost other people. It's definitely cost livelihoods. In terms of our research programs, we spent a lot of time reaching out to find out what sort of support we could provide. Often it was 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.
Claudia Vickers:
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. 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. I think relative to the rest of the world, I have many international friends who've been literally out of the lab for a year. We haven't had such a bad impact. We've been able to support our people most of the time through those, those pandemic inflicted delays.
Lydia Morrison:
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 Vickers:
Yeah, absolutely. 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. 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. Now I'm not traveling at all, but I'm still doing almost everything I would otherwise do apart from the in-person conferences. 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 night, so it can be a bit challenging and terms of time zone.
Lydia Morrison:
Absolutely, much like this interview. 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 Vickers:
Yeah, sure. 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. These isoprenoids are really fascinating. They're a really large family of natural products and they include small volatile molecules and long complex molecules that are heavily decorated. 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. Carotinoids, your reds and yellows and oranges, these are all in the isoprenoid family.
Claudia Vickers:
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. It's emitted in teragram amounts per annum into the atmosphere from the biota. And the question is, this is an enormous amount of carbon going into the atmosphere. Isoprene isn't a greenhouse gas per se, but it interacts with other gases in the atmosphere that will otherwise soak up greenhouse gases and increases the residence time of greenhouse gases. It's really important in global atmospheric value with geochemical cycles, but we didn't really understand properly why plants made that molecule. I was interested in understanding better the physiology around that. It turns out that it's basically part of their stress response system and interacts with their antioxidant metabolism and helps them deal with oxidative stresses. That was the piece of work that I was doing to learn about isoprenoids and start working in that space.
Claudia Vickers:
And then when I came back to Australia, I became interested in this metabolic engineering thing. Metabolic engineering is essentially redesigning, in this case microbes and their metabolism, to channel carbon from the feed stuff that you give to them all the way through to the product that you're interested in them making that has an industrial application. It turns out that isoprenoids have many, many different industrial applications. There's such a large and chemically complex and diverse group of natural products, but they have many different applications. They range from pharmaceuticals through 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 biofuel. We have a whole range of things that we can make.
Lydia Morrison:
That's amazing. So what has the success been like in reprogramming microbes to produce these?
Claudia Vickers:
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 is the mevalonate pathway, which is a pathway that's found in us as well. So it's quite interesting study from a physiological point of view and for a lot of different applications. What we have found is that isoprenoids exist in different classes that are related to the number of carbon molecules in the isoprenoid tail. Some of them are really challenging to get to, so we've had to develop mechanisms to bypass or redirect carbon at specific nodes and the isoprenoid pathway.
Claudia Vickers:
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 where 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. That's delivered in grams 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, a solvent or a polymer. We're really excited by that because that's real world impact.
Lydia Morrison:
Absolutely. 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 Vickers:
Really good question. It's called the Isoprene Rule, and I'm not going to try and pronounce the name of the guy because 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 on the mevalonate pathway or that other pathway, it makes five carbon parental phosphates called isoprenteryl pyrophosphate and dimethylallyl pyrophosphate and their isomers. And if there are five common 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. That's why you have five, 10, 15, 20 carbon, et cetera, modular isoprenoid compounds, there are others you can take individual carbons away and get different carbon numbers, but that's the basic background of why there are modular like that.
Lydia Morrison:
That's interesting. I love the simplicity in nature that turns up in even the most complex scientific processes.
Claudia Vickers:
Yeah, it is. It's actually, I think, unusual nature. So that's the basic tenet behind synthetic biology is that we can treat biological systems 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. 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 Morrison:
Yeah. I think what you're describing is really the basis of synthetic biology, right?
Claudia Vickers:
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 Morrison:
I think it's a great application of the theories of computer science and electronic programming to biology, and it's amazing how similar the two systems can actually be.
Claudia Vickers:
Yeah. And the thing about this is that it's truly interdisciplinary. It's blending of biological engineering with automation and robotics and artificial intelligence to dealing with big data sets. 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 Morrison:
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 Vickers:
Yes, very much so.
Lydia Morrison:
Where do you see synthetic biology heading in the future?
Claudia Vickers:
Well, I think the cutting edge of synthetic biology now is that nexus of big data and artificial intelligence and bioengineering, of course. 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. How do we feed it into that Design-Build-Test learn cycle? That's one of the areas that we're working in, at the moment, and in terms of where are the next Horizon Three science questions, exploring into that space, I think, is really very exciting.
Lydia Morrison:
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 Vickers:
Well, the immediate good thing is not traveling so much for me. Well, 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 often and around the world and onto the next thing. I've spent a lot more time with my family on a day-to-day basis. I have two small kids; they're nine and six, and they miss me a lot when I'm traveling. It's a challenge always to be in a position that's relatively senior and involves a lot of travel away from home. When you're doing that with children, then that's a challenge as well. It's been a lot easier in that period of time from that perspective. So that's my good story.
Lydia Morrison:
Yeah. I think that's wonderful. I think that that's probably a lot of people's good stories. I think that one of the lessons that's come out of the pandemic is that we can collaborate globally and communicate. We can do all that 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 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 Vickers:
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 Morrison:
Absolutely. Thank you so much for joining me today, Claudia.
Claudia Vickers:
Thanks, Lydia. A pleasure.
Lydia Morrison:
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.
