October 03, 2022

Microscopic eco-warriors

By Conor McKechnie and Dodi Axelson

Microscopic eco-warriors

Plastic and pollution are two issues that impact our planet. It would be easy to despair but once again biology has come to save us. The Alper Lab at University of Texas at Austin has engineered a plastic-eating enzyme which can shorten plastic degradation from hundreds of years to 48 hours.

We speak to Dr Hal Alper, Professor in Chemical Engineering at UT at Austin, who engineered this heroic enzyme.

We also speak to Marco Poletto, director and co-founder of EcoLogic studio, which is a design innovation company specializing in biotechnology for the built environment. He explains his use of microalgae to create streetlights, playgrounds, and biofilms on the outside of buildings which can capture 20 large trees worth of CO2 every day.

Show notes:

Timelapse of the plastic degradation, courtesy of University of Texas at Austin

DODI: Conor, have a look at this video. This is a time lapse of plastic degrading.

CONOR: It looks like a takeout tray, doesn't it?

DODI: It does, like the old TV dinner tray?

CONOR: Yeah, exactly.

DODI: But for listeners, we're going to put a link to this in the show notes for you to see for yourselves. And obviously this is sped up. But a question for you, Conor, how long do you think this took in real life?

CONOR: Oh, I don't know. I mean, it can't have been the actual hundreds of years that plastic takes to degrade because, like no cameras and so on. So, I don't know. Months, weeks?

DODI: 48 hours!

CONOR: No, way.

DODI: And that is thanks to an engineered enzyme that was developed by Dr. Hal Alper at the University of Texas at Austin.

CONOR: Ah, so is he a biologist? And is biology saving the world again, cleaning up our manmade problems.

DODI: Indeed. And that is what matters today on this episode of Discovery Matters. Microscopic eco warriors welcome.

CONOR: Okay, so you mentioned Dr. Hal Alper there. Who is he and where is he from?

DODI: Well, he is at the University of Texas at Austin. And he started working on this project as a sort of confluence of events.

DR HAL ALPER: So, our lab in particular has always been interested in trying to find sustainable solutions for bio manufacturing. This is new ways to be able to create chemicals and fuels, new ways to move away from chemical processing, but rather more sustainable, green, microbial based or enzyme-based processes for this. So, we're interested in engineering waste, biology seems to be a solution, we engineer biology. And then in congruence with that, a lot of the developments of these machine learning algorithms on our natural psychology and natural science side have really enabled this combination of events, 'hey, let's combine forces. Let's take these algorithms, let's take the passion for engineering cells and engineering enzymes and bring that together and do something impactful.'

CONOR: If I understood correctly, Dr. Alper is what created some form of like plastic eating super organism.

DODI: Not quite an organism, it's an enzyme.

DR HAL ALPER: So, this enzyme is not a living organism. So, it's an enzyme, it's the protein that's functional, that will be able to degrade in particular PT, which is a form of plastic. There is a lot of plastic waste out and around, and biology over time it can find a miraculous way to be able to utilize everything that's out there. And so, there are some microorganisms that can begin to colonize on to plastic water bottles. And then people have discovered that there are enzymes that give rise to that function and those organisms.

DODI: There are others who started to work on engineering those particular enzymes, not from microbial use, but for industrial use.

DR HAL ALPER: And that's kind of where we jumped in.

CONOR: And who is we in this context?

DODI: We are the Alper Laboratory at UT Austin. And they saw all of this is a great opportunity to merge different types of research. We love to talk about cross functionality, don't we?

CONOR: That's absolutely spot on. All sorts of applications of different disciplines to kind of make things happen, I love that.

DR HAL ALPER: To bring in machine learning, to bring in protein engineering, to bring in biochemical engineering, and bring that together to create an enzyme that was extraordinarily active, that outpaced pretty much everything that's out there by multiple fold and could also work at lower temperatures and at more neutral pH conditions. That really leant us the ability to take this enzyme solution and degrade pretty much every post-consumer PT plastic waste that we threw at it. And that I think is the remarkable fact that we can actually find a way to re-circularize essentially this plastic that has already been put on the environment.

CONOR: So, the plastic he's talking about here is what we know as like PET or polyester plastic, is that right? It's the kind of plastic that we all see all around us in water bottles and plastic cups and so on.

DR HAL ALPER: Yeah, it's everywhere else. I think you'll recognize it as well from the cookie containers or muffin containers that you use or the plastic that you need to use those can openers for to almost open up packaging for razor blades. So, it is around quite a bit more than just the water bottles.

CONOR: So, how does the machine learning piece come into all of this?

DR HAL ALPER: Yes, so the machine learning approach is developed out of the Ellington group in natural science. And there, it was the recognition that we can begin to learn from biology. Biology gives us a whole catalogue of different proteins that we can investigate. And if you start to throw these proteins at a machine learning algorithm, you can begin to learn what makes a protein stable, what makes a protein good if you will. You can kind of get some of these details in terms of looking at the microenvironment around the various different amino acids that are within that protein.

DODI: Now by looking at 1000s and 1000s, of different proteins, Hal and his team can learn patterns about what certain amino acid residues like to have around and in that microenvironment.

DR HAL ALPER: So, once we've taken that algorithm, we can then apply that to this particular enzyme, this PETase enzyme. It is not a very stable enzyme. It decays itself at higher temperatures, it doesn't have prolonged activity. So, they had those challenges that we recognize that this is probably not a very stable protein. So, chances are there were residues across the board that were not really most optimal. So, we kind of took this machine learning approach and applied that to this protein and went through across the entire protein and looked at every single amino acid and queried as to whether that was in an optimal environment or not.

DODI: So, they've identified mutations that they can make on an enzyme that will improve its function and stability.

DR HAL ALPER: We went through and experimentally validated those, down selected, and then eventually created through a combinatorial approach our final enzyme variant.

CONOR: Okay, so it sounds like machine learning is really opening the door to us to sort of evaluate any types of mutations, any types of enzymes are really, really broadly to see what they could do.

DODI: Exactly. And it gets rid of limitations that were there before.

DR HAL ALPER: It makes most sense to just home in on just the active site of that enzyme, essentially the mouth of the PacMan, if you will, and kind of focus right on there. But this allowed us to find mutations that were far away from that. So, regions that prior research had not looked at, because we looked very globally at this entire protein. And that really, I think, makes a huge difference in terms of the leaps of function that we can make in protein engineering.

CONOR: So, look, in the biopharmaceutical and life sciences industry, there's kind of a connection here, isn't there?

DODI: What do you mean?

CONOR: Well, we're looking at proteins and looking at how we can apply them to treat diseases in our bodies. Is this too much of a stretch, couldn't we make a protein and apply it to kind of treat the terrible infestation that is plastic on our planet. So, Dr Alper is kind of super anti-plastic, which is great. But does plastic have any value for him?

DODI: We asked him that question. So, let's hear directly from him.

DR HAL ALPER: Plastic can be used, it can then be deconstructed back, which essentially what this enzyme does, it deconstructs it back to its starting point. From which we can rebuild that plastic once again, or we can say this is the end of the life of this carbon now let's take that monomer and do something else with it. We can create it into a fuel or create into a chemical. Theoretically, we can create it into a pharmaceutical even. So, you can really think about using that carbon in different ways as opposed to just throwing it out into landfill that eventually leeches somewhere else. We don't want that. That's not circular.

DODI: Instead of this open circle Hal says there are a couple of different routes for recycling.

DR HAL ALPER: There's traditional melting down the plastic and then reforming it again. The challenge there is that when you melt, you're mixing everything together. You're not going to get the same property trait as you had initially. And especially in a lot of the life sciences applications, it's critical that that plastic - raw virgin PET or raw virgin plastics in general -have better traits than the recycled version. Being able to break this apart to its original building blocks and build it back up again. Each time in that cycle, we're able to regenerate that virgin PET. So, we're able to regenerate that same performance trait that it had from the beginning. So, we can almost think about this in terms of using this in single use type of manner for the single use bioreactors or single use chromatography systems, you can use that and have the performance you want, break it back down, build it back up, and you have that original single use element once again.

CONOR: So, it's almost like the enzyme is like the old timber on the VHS recorders. We are so old. You could press the old rewind.

DR HAL ALPER: To some extent, it goes back to where it started, not all the way back to the oil and petroleum that it started with, but back to the building blocks essentially. I liken it also to thinking about plastics, to some extent, are kind of just beads on a string. And what this is doing is just pulling the beads apart, so then you're left with that pile of beads once again. And sometimes you can string that together and make that same necklace that it had before. Or sometimes you want to use that set of beads and make some kind of interesting craft for Mother's Day, right?

CONOR: So, as we both know, we are destroying the planet as a human race. And then along comes Dr. Alper and his team and they seem pretty hopeful. So, where does that hope to come from amidst all this sort of eco and climate Armageddon?

DR HAL ALPER: I think we're getting to the point where we have the ability to undo some of the damage that we've done. As long as we're not doing damage faster than their ability to undo that. I think there's great hope for the future and optimism. And partially also biology has been able to find a way to sort of, very slowly but, begin to deal with this. And it hasn't been that long if you think about it. Plastics have not been around for very long compared to the grand scheme of humans being on the planet, let alone microorganisms. And so, biology can find a way. But it takes time. So, again, it comes down to this balance. I think science, biology, and the advances that are happening certainly in machine learning are really enabling us to find unique solutions.

DODI: Okay, Conor, let's leave the world of plastics and enzymes for the moment and focusing on another microscopic eco-warrior, microalgae.

MARCO POLETTO : We started to work with, with microalgae and cyanobacteria more than 10 years ago.

CONOR: And who's this?

DODI: That's Marco.

MARCO POLETTO : Yeah, I'm Marco Poletto. I'm director and co-founder of EcoLogic studio, which is a design innovation company, specializing in biotechnology for the built environment.

CONOR: So, what's Marco up to exactly?

MARCO POLETTO : Our first idea was that we could then perhaps, begin to look at these organisms and not only as something that exists there in the kind of murky waters of some canal, but that actually could become a new medium, a new protagonist, for the future city.

CONOR: So, what can microalgae do in urban environments? Are they going to help improve the health of our cities in some way?

DODI: Yeah, one of the major ways that the Ecologic studios work has been used is through what they call this algae curtain. And that's where a building is given a new skin, a bio plastic film which contains algae, and these films can capture CO2 from the atmosphere at an estimated rate of about a kilo a day. So, that is equivalent to about 20 large trees just cleaning the air.

MARCO POLETTO : So, in terms of the possibility, the efficiency of these organisms, they are quite exceptional. The reason for that is that microalgae are single celled creatures, right? So, they are a microorganism, their entire body and metabolism is photosynthetic and kind of entirely devoted to converting CO2 and other minerals into biomass and releasing oxygen. So, that's why we started to promote the use of microorganisms more and more in the urban realm. Because being microscopic for them, the habitat that you can create in a little vessel, it's perfect. They don't know what happens around them, as long as they receive the light and CO2 and the minerals, they are happy. And of course, the biomass that can be harvested from each of these vessels also has specific properties.

DODI: There's an added benefit.

MARCO POLETTO : Now, we worked with different strands of algae, the most commonly used as nutrients to feed humans are the spirulina and chlorella. They are proteic, and they have a very rich mix of nutrients within them. So, they are normally then dried and transformed into powders, this would make it possible for pretty much anyone to grow them within their home, even if they live in a flat and harvest them regularly. And we have realized that a vessel that contains about 20 liters of living cultures can grow enough biomass to feed small family of three people. And the significant aspects here is the extreme space efficiency of this organism. There are no other microscopic plants that in such a small amount of space, and with so little resources, can metabolize such a large concentration of nutritious substances.

DODI: Today, Marco works in a kind of intersection of different disciplines, we're coming back to this cross-functionality which is awesome. So, you have architecture, you have engineering, and then there's this artistic side.

CONOR: And that's a lot going on, isn't it brilliant? Because all of these delineations between disciplines, they're just essentially like artificial barriers in our minds.

DODI: Yes, they are.

CONOR: Yeah. So, how does he navigate the different scientific aspects of all of this and bring it to his work?

MARCO POLETTO : First of all, I think that one of the beautiful aspects of being a designer is that you don't actually need to understand everything.

DODI: So, essentially, what Marco and the rest of his team are doing here is creating a platform that uses design and space and special language.

MARCO POLETTO : And this is where architecture comes in as well to allow for specific fields of expertise to come together. And also, of course, now after, you know, 15 plus years of doing this we have learned a lot as well in the process. So, we kind of have our own unique know how or unique expertise that blurs or brings together knowledge from microbiology, computer science, architecture, design art, but again, we are not experts of any of these fields by any means.

DODI: And this was so amazing to hear about. So, one of the things that stood out was the idea of replacing the idea of how we light today's streetlights with power from algae.

CONOR: Okay, this is really exciting. And cyanobacteria we know are kind of responsible for all essentially of the oxygen on this planet in the very early stages of its formation. So, this is super cool.

DODI: It is and, you know, Marco and his team are inviting anyone in London to see and participate in his work.

MARCO POLETTO : We have the Air Lab at the Building Centre now open in London for three months, just off Tottenham Court Road in central London. We have created this Air Lab where essentially part of our team will work live capturing carbon and pollution, re-metabolizing it into bio polymers and 3D printing biodegradable products out of it. So, you will see the whole process taking place in front of you. And you will be able to just work side by side with our folks and discuss with them, chat, and ask question. So, really an idea to show that every space, every urban space, can be turned into a lab if we want to and it can become a space of innovation and of change. And I think that that kind of participatory nature is fundamental.

DODI: So, obviously, this is on my list.

CONOR: Absolutely. Me too. I'm so going, can I have this stuff in my house?

DODI: Maybe, maybe. See if you can meet Marco in London. There are lots more projects that EcoLogic studio is working on from streetlights, biotech labs, and even children's playgrounds. This is absolutely amazing how biology and urban settings come together for a healthier future.

CONOR: What if we brought EcoLogic studio and the work of Dr. Alper at UT Austin together and they did something really cool. Okay, I'm getting a bit excited, but look it does make me feel a little bit better that some people in some places are doing something towards solving the challenges on the planet rather than just creating more and using science and art and design and creativity to do it.

DODI: And it's so accessible! We can see it and we can participate in it.

CONOR: I just love that.

DODI: Our executive producer is Andrea Kilin. This podcast is produced with the help of Bethany Grace Armitt-Brewster. Editing, mixing and music by Tom Henley and Banda Produktions. My name is Dodi Axelson.

CONOR: Make sure you rate us on Spotify or whichever platform you use to listen to our podcast. If you're listening on Spotify, do answer the poll under the episode description. We'd really like to hear from you. We'll see you when we come back with another episode of Discovery Matters.

DODI: BioPharma is a patient centric industry. And if you want to hear more from the patient, then have a listen N-Lorem's brand new podcast 'The Patient Empowerment Program'. This new podcast series hopes to foster a community of care for nano-rare patients by supporting and empowering them as they navigate understanding their disease.

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