Tag: gut microbiome

Inside the Microbiome Startup Industry

 

The microbiome is a very special opportunity because it allows you to create products that potentially have the efficacy of a drug, but the safety of a probiotic
-Colleen Cutcliffe, PhD

 

The Fall 2021 Genome Startup Day event, Inside the Microbiome, took a deep dive into the origins of several microbiome startups. Starting with a fireside chat, Ivan Liachko, PhD, cofounder and CEO of Phase Genomics, and Dr. Christopher Mason, Professor at Weill Cornell Medicine and cofounder of several startups, discussed Mason’s passion and recent projects relating to the microbiome. From children licking their way around their environment to sending fecal samples into space, Mason described his journey into the emerging field of the microbiome. He continued onto some of the early challenges in transitioning from academia to industry and shared his advice to any graduate students attempting to do the same. Mason also noted the improvements being made in this field, making it easier for startups to collaborate and progress.

 

“It’s become much more of a startup-friendly, entrepreneurial ecosystem in most academic centers”
-Christopher Mason, PhD

 

Next, Dr. Kirsten Sanford, host of This Week in Science, led the panelist discussion. Colleen Cutcliffe, PhD, cofounder and CEO of Pendulum Therapeutics, described her motivation to begin a microbiome company. She began with an anecdote about her daughter overcoming illness and inspiring her shift in focus from publishing papers to creating health solutions. Momchilo Vuyisich, PhD, cofounder and CSO at Viome Inc., shared similar experiences he had aiding people to improve their health in miraculous circumstances. Coming from a different field of study, Nick Greenfield, Head of Microbiome at Invitae, described his experience breaking into the industry and how he founded his initial startup, One Codex.

 

View the event recording below for the full conversation and more insights into the world of microbiome startups.



Stay up to date with Genome Startup Day on Twitter and watch previous events on the Genome Startup Day website.



Transcription

Ok. Welcome, everybody. We’re going to get started here for today. Sorry, I had to close my other tab. So good afternoon, everyone. My name is Kayla Young, and I am the chief operating officer at Phase Genomics. Thank you for being here.

Our next Genome Startup Day event. So, for those of you that are new to our events, Genome Startup Day, it’s designed to be a community building catalyst for genomics startups, founders, investors, service providers, media, and jobseekers. So please stay connected with us via Twitter.

@GenomeStartup I also put that in the messages and keep up to date for future events so quickly for kind of some run of show things and housekeeping. We will do question and answer at the end of both the fireside as well as the panel.

So please put those questions into the chat box on the right side of your screen. Additionally, for every question asked will be entered into win Phase Genomics socks, so we will announce those winners throughout the sessions. But I will follow up after to coordinate that.

So, ask those questions and join the conversation. And then finally, last but not least, I would like to extend a very big thank you to all our sponsors that make this happen primarily s2s PR, which helps put on these events for us, but also Agilent, Illumina, Pacific Biosciences, Alexandria LaunchLabs and CoMotion without this sponsorship.

This would not be possible. So, with all of that behind us, I would like to introduce our fireside chatters and my boss, Ivan Liachko, CEO and co-founder of Phase Genomics, who will be talking with Dr Chris Mason. So, Ivan over to you.

Hello, everyone, thank you for coming. Thanks, Kayla, for the intro. As you can see by my fancy attire that we’re having a fireside chat and I’m very lucky today to have with me Chris Mason, who many of you are familiar with.

Chris Computers Chris is an Associate Professor of genomics, physiology and biophysics at the Weill Cornell Medicine and director of World Quant Initiative for Quantitative Prediction, as well as an affiliate of Memorial Sloan-Kettering Cancer Center. Rockefeller, Harvard Med School, Yale Law School.

And there’s like three more pages of this stuff. If you’re not familiar with Chris, Chris is super engaging speaker. I’ve seen him talk many times at different conferences. He addresses really cool topics, most notably his interaction with Nassau and Nassau, not Nassau, NASA and the others, the space poop work he’s done with Kelley twins and

others. And of course, recently a lot of microbiomes of sort of cities and built environments. He can see, I’m just trying to read something. He’s got like 1,000,000 awards. He has been on like ABC, NBC, CBS, Fox, CNN, PBS, Nat Geo.

He’s also one of the reasons why I like to have. I like to, you know, I wanted to have Chris on here is because the purpose of this event is really it’s a startup event, but it’s a little bit different because the goal was not so much to educate people about, like how to raise money and how

to do startup mechanics. But really about that transition for scientists, that has to happen at some point between academia and industry. Like at some point we as geneticists have to come out of our earlier kind of academic shell and decide to spin out companies.

And there are so many challenges. And this event was really about talking about it, not about so much educating you, how to do it and filling out the forms and IP and all that stuff. But really like, what’s it like?

And what’s cool about Chris is that he’s a super accomplished faculty. He’s doing tons of science. He’s in the news all the time, but he’s also very involved in the commercialization of technology is associated with lots of startups, and that’s why I really wanted to bring him in here.

A lot of times what we do is we have founders who a lot of times they’re like juniors and we get their perspective, but of course, they interact their faculty all the time. And so, I want to know what it’s like from a faculty perspective and faculty, as Chris, as you know, range all over the place from

being super startups and commercialization to being straight up hostile to it. And like, you know, and so we want to just talk about it and like, get your opinions. And obviously, if you were super hostile, I wouldn’t have.

Right, right?

So, I’m assuming you’re pro. So, so yeah. So, let’s first off, this episode is about the microbiome. You know, why is it about the microbiome? The microbiome is cool. I work with the microbiome, and I organized the show.

So why do you do so much microbiome work? What’s like? What’s your favorite thing about it? Like what? What draws you to that particular topic?

Yeah, the number of things, actually. And can you hear and see me? Okay, sounds amazing. OK, great. So, a few things. The real inspiration came from two events that happened around the same time as that one. I just became a father and saw a lot of microbial interactions from a new lens, which is just, you know, infants

crawling on the floor, licking things, putting everything in their mouth. I actually talked to our daycare when we first dropped her off and said we should do an experiment. There’s a lot happening here in terms of microbial transfer.

And of course, then I realize I immediately was that creepy, weird scientist. That’s like, why is he planning experiments on our children so we didn’t do that because that would have been a little weird, but the thought never left my head.

The other thing that was happening at the same time is we started doing a lot of whole genome sequencing clinically in 2011 2012, and there are always fragments of DNA, even if you know, especially you get from a skin sample.

But even sometimes blood samples that didn’t match up to the human genome part of it because the human genome is incomplete. But also, you will have microbial sometimes contaminants that are there, but sometimes actually mediating biology. And they’ve recently been found inside of tumors.

They’ve been found, of course, in gut samples and skin samples, but even circulating in blood. We now have a company you one of my companies, Biotia is working on ways to sequence microbes from anywhere, including CSF or from things that normally have blood that you wouldn’t think would have that much unless you’re really sick.

There’s actually trace signal that’s there every time you sequence a sample, that’s you human microbial really in any kingdom of life. So, as I became more and more of a clinical geneticist in practice and also in startups, I just began to realize you have to be really kingdom agnostic to do the best possible science.

So even if you’re a computer empirically, wonderfully, trained human geneticist, if you only look at the human genome as a geneticist, you’re actually really crappy human geneticist because you’re missing a lot of biology. So, to understand health, wellness, disease trajectories of any of them, you have to look at it from a kingdom agnostic or kingdom inclusive view

across all domains of life.

Yeah, no, it’s really, it’s really cool. Like the thing that drew me to it, honestly, was that just the fact that if you think about like, you know, if you think about diminishing returns of discovery, right? Like we’ve done a lot of work on cancer, we’ve got a lot of work on human biology.

But like if I see sequence, if I scoop a little thing of soil right outside my like, it’s all new. Like, it’s like an unknown and it’s not like we invented it. It’s always been right. Like, we just.

Now.

Everything we do, we just have not had the tools to really to really measure it. Yeah. What about like the flashy projects? So, like, what was your favorite thing about the space poop? And like, how long did it take to like, get into that whole thing and become like, then that’s like, are you?

I’m assuming the next stage is going to be terraforming Mars with just sending them like poop and dumping it on there. Yeah.

Matt Damon. Yeah. I mean, it’ll take a while, but it actually did just publish a book called The Next 500 Years, which is a five-year plan to actually get people on to Mars and other planets, which involves a lot of microbial engineering, potentially even human genome modification or engineering to make it feasible.

So, I think there is a lot that we can do that we’ve just learned the tools do some of the genetic manipulation. Most obvious is CRISPR or some of the new Amiga systems that can do gene editing, but also just the catalog of genetic what’s in our DNA toolbox of just functional elements from all microbes.

Other species that we can use and deploy is getting bigger every day. And that’s kind of it’s really exciting as we are. We’re still in in this discovery phase, but it’s ramping at a super exponential pace. So, we can really sort of imagine doing this for, you know, anything from as simple as microbial monitoring on the space

station, which we’ve been doing for a few years. And most recently, I know Jack Gilbert, Robin, I’ve done some sampling up there as well. So, like more and more teams are thinking like, well, what can we learn from the microbes in space when we bring them back down and sequence them or even sequencing in space, which we

published a few years ago? They’re actually different. They evolve quite quickly. It’s a unique selective environment, which, you know, it’s not too surprising when you think about it. But you know, everywhere we look, including the space station, there’s new things to discover.

And I think a lot of the space projects are my favorite because I consider it my life’s work to try and get that goal.

But we’re like, I got hit by a bus tomorrow. At least I would have sequenced poop in space.

That’s right. That’s right. At least I got that. Check that off my list.

And yeah, the first time we sequenced the platypus, that’s what I said to myself. If I die today, I can say we sequenced a platypus one.

Funny you mentioned there is a bus rule in the labs that if you get hit by a bus, the work has to continue to document that. We’re very careful with the lab notebooks. We call it the bus rule in lab.

Which is that’s a that’s a that’s a good one. Yes, testing it might be a little hard, but what do you think will be the next thing? The next? What’s the next big thing in the space?

We just finished the inspiration for mission, and now we’re planning some other missions with Axiom. I going to have its own private space station by 2024. So, I think I think the next big thing is this commercial space sector, which is kind of a new space race.

So, we work with the medical ops team at Space X a lot over the past nine months to set up the first aerospace biobank and set up some of the very first protocols for sampling for private astronauts. What’s kind of amazing now is it’s going to be like Axiom is just space station.

So, if you want to do anything up there, as long as you can afford it, you can fly it up there and do whatever you want. So, it’s in the ranges of tens of millions of dollars, or sometimes hundreds of millions of dollars, depending on how long you want to go up there.

But you know, if you can afford it, you can go do whatever you want up there. So, we’re working. Yeah, we’re working on a bunch of interesting missions where one person wants to go for 500 days and stay in space for the longest time ever to simulate a trip to Mars and back.

Basically, other people want to do manufacturing in space. A lot of people want to do, you know, microbial engineering, even in space or organoid work that’s already happening. So, I think there’s a lot in the space sector is opening up a lot and it really was hard to get up there and difficult before.

But now it’s going to be it’s going to be pretty routine, which is pretty cool. So, if they have any experimental thing to do, it’s possible.

The space. All right, let’s talk about startups. So, as I mentioned, you are super active and super successful. You have a lab. You know, how and why did you get involved with startups?

I got my first startup failed, which is important now. I think a lot of people feel like it was one called Genome Liberty, which is right after the AMP versus myriad decision in 2013. We thought, OK, now genes are no longer patented.

We should make it so anyone can sequence any gene they want. I want to like a run down the streets of Manhattan and say, you get a genome, you get a genome, you everyone get the genome like Oprah.

But I was just so. Saying it because it had really democratized access to people’s own genetic information, and so we started a company that was the beginning of kind of a direct-to-consumer genetic testing company like 23 and me but more focused on actionable genes like pharmacogenomics and cancer genes, which ended up this idea ended

up being something like what color genomics is doing other companies. But at the time, the FDA was really clamping down on DTC genetics companies. And so, we and they even been sending letters to 23 and me. So, I thought at that time with a newborn child and a fairly young professor, do I spend a lot of time

and regulatory back and forth with the FDA, with the company that has very little funding? We did a crowdfunding campaign to get it off the ground and got some money, but at the end it was just some point to do a startup.

You need more than one or two people who are doing it part time to really get off the ground and what’s often called fire in the belly. And some of that’s like, I’m going to leave my job and have this be my job.

You don’t want to get to faculty doing it like 5% of the time. It’s never going to take off, right? So. So but the concept of it I really like is that there are ways where you can’t do it at an academic lab.

And academic labs are great for many things, for a lot of the pure discovery, pure development of new protocols, but to scale them or to get them out to the mat, a large number really have to do in a company setting.

You have to really, you know, like you can’t do, you can’t work with 1,000,000,000 people or get things a vaccine, for example, to 1,000,000,000 people from a small academic lab or even a big academic. That right, it’s just not it’s not worth for.

And so, I really start to think more about how do I really launch some of the things we’re tinkering with in lab and get them into a commercial setting? And that’s actually what led to Biotia was getting all the metagenomics work we were doing.

How do we make it so we can use this as a diagnostic and really get it to market? So, I think it’s a classic pinpoint let it pay pain point. And at what point can we go from a cool concept in the lab?

It’s working. We know it has capacity to change how we treat a certain disease or do diagnostics, but you have to at some point either set up as an LDT in your own CLIA lab or actually start a lab if you really want to go in that direction.

So yes, we’re going to get it be. It’s basically if you look around the world and the thing that you want doesn’t exist at some point you just have to either buy it or build it, and it didn’t exist, so we wanted to build it.

That’s awesome. And I think. There are two points that you made that I think are super important for our audience. one is that Chris Mason had a startup that failed. one of the things that startup founders and just startup people in general deal with all the time is this bias of like, you only hear about the successes

, but actually, failure is super common. And so, anyone who gets anywhere near what doesn’t seem like success starts having all these anxiety issues right? And so, I wanted to highlight that like, you know, like, it’s normal. These are every startup is an experiment, right?

And you don’t know what’s going to happen and you think, you know, you think you’re going to nail it out of the park, but you don’t really know, ever. And so just highlighting it for people in the audience maybe who are considering or thinking about it, like it’s normal, it happens and as part of the ecosystem.

And then the other thing that you mentioned that was interesting to me is this prime mover idea is that like you like you need; you need people who are going to go all in at some point.

I also when I started phase, like I kept one toe in academia for a long time. Eventually, I had to jump. And you know, and the faculty are generally the ones who do the jumping because you guys have good, solid jobs and you’re right.

Because you’re tenured faculty like, well, why would I give up this literally like guaranteed lifetime job? And so, it’s got to be. And also, I have to look for people who left my lab and go to start companies.

I also it’s going to be a good opportunity to look at an actual capitalized company where they’re going to do a real job, not, oh, I think we’ve got some money will go look for more money later. You really have to make sure you launch with a full, full tank when you hit the road.

So, so let’s talk about that a little bit, because I guess I mentioned sort of the relationship between faculty and students who go into industry can be touchy sometimes and sometimes people, they want to, you know, sometimes they want to start a startup, but sometimes they just want to go work for a company like, you know, work

for Agilent or Illumina or something. And how do you like, how do you what sort of. Interaction, do you have how do you relate to students who are doing that kind of stuff? Like what do you do to encourage and discourage them?

You know that kind of stuff.

I think mostly they do. I mean, the interactions depend a lot on the person, of course, it’s a little everyone’s a little unique snowflake in a way, but the one thing I do is I discourage people, feel like a first-year grad student and think, oh, I’ve heard about startups, I want to make my own company.

I think, well, you know, give it a I mean, you can’t like you could be the next Steve Jobs or Bill Gates, but the odds are that you’re not like, you know, you may not need to finish college or grad school and just jump right in, you know, maybe, but you got to play the odds a little

bit. And then also, you can still do some of the tinkering and development and IP development at. I mean, I think most people I encourage them say like file patents when you’re a grad student or postdoc. The university loves it and then you can license that IP to start.

A company in the UK have a good foundation for the company rather than. I have an idea and I need $10 million to get off the ground. If you actually have IP, investors will like that a lot more. Not surprisingly, and so will your customers because of something that they’re using, that’s unique.

So, I think the I encourage them to file patents encouragement to not do their first year of grad school, but that they should, you know, when you’re getting towards the middle years to start to think about if they really want to go that direction.

So, try to be as encouraging as I can. And you know, I actually wish people had told me, hey, if you have an idea, go meet with the tech transfer people out of university because they can help you file patents when you get out to the private market.

Filing patents is bloody expensive right after it’s 20 to $50,000 per patent prosecution. Depending on how complex it is. The university does that for you, of course. Then you have to pay them later to license it.

But at that point, somebody else was paying for it. So that’s another really, really good point. You know, when you’re and maybe this is helpful to someone in the audience. But if you don’t know if you’re a grad student or postdoc, and you invent something the university owns that invention or what that means, is that they

will be the ones paying for patenting it if you convince them that it’s worth it. And so, yeah, it’s hard to imagine a scenario where it’s you shouldn’t patent.

Even for it is like, I don’t know if my idea is that good, but just go pick up the phone and call the patent attorneys who look at this, and you’d be surprised how often things are really straightforward can lead to a patent.

Yes, because no one’s gone for them.

Yeah. And if nothing else, you learn a lot of stuff. Like the other thing about startups is that like when you go through the process, you just like the first six months is like the most learning intensive process period of your life.

Like you’re learning things that you’ve never heard about before or maybe you’ve heard of. Have no idea what they are, you know, and patents is one of those things, at least, you know, it’s something you should be aware of.

It’s part of our ecosystem. What do you think like, what have you seen in terms of the general ecosystem, like for other labs? Like what have you seen in terms of kind of how folks, you know, you know, New York is very high tech, obviously.

Like, what do you how do you see the shift happening like that, like you told your own story about sort of startups and interacting with students? What about everybody else? Like, are more faculty becoming into it? Or like, what?

What do you see?

Yeah, it really is. It’s become much more of a of a sort of startup friendly, entrepreneurial friendly ecosystem in most academic centers that I’ve seen, especially in the past five or six years. You know, there’s even a dean who’s just about biopharma collaboration and entrepreneurship at Cornell, at the med school.

There’s also one at Cornell up in Ithaca. So, there are, you know, now dean level appointments of people who think we should just encourage this, encourage Google to come up with ideas. Also, the NSF and the NIH and DARPA all help support startup companies.

So, NASA even has something like an SBAR fund, which is a small business innovation or research award, but it’s a NASA version, so almost every federal agency really applauds and encourages people in academic sites to come up with an idea, get it capitalized, get it off to market, and we’ll give you grants for it, non-dilutive capital

coming from the government to help get your company going. So, I think that’s always been there. But I think in the past few years, you know, 15, 20 years ago, there was much more of a, you know, academia over here in pharma and industry over there, and they shouldn’t, you know, engage with each other.

But I think we’ve just realized there’s a lot more to be done that can be done faster if you do it together. So, I think there’s a lot more collaboration coordination between academic medical centers and industry and pharma and startups.

And it’s gotten it’s encouraged. You know, people, you know, encourage entrepreneurship in a way that I’ve not seen. I feel that wasn’t really the case seven or eight years ago in New York, in particular, is now a multiple incubator startup hub.

There’s Harlem, Biospace Spaces, Alexandria Labs, there’s cure building that just launches. You know, all these spaces, the bio that’s now the one where there’s a lab space. You can get a startup, get some space, get going and have a startup company.

Yeah. So let me do let me do a couple of questions from the audience. So, I have one. So, following up on the patent question, if the university owns a patent, then how do you build a business on that?

So, I mean, there’s a technical answer, which is you start a company and then you get a license from the university. But sort of. You know, follow up on that, like, what do you guys, how much work and maybe how much resistance have you seen, like if somebody’s getting something via Cornell and then they want to

go find the company? How difficult is it to get a license? That process can also be touchy sometimes between.

Yeah, see this question. And it does depend on the university. Generally, they will. They actually are much happier, more happy to file a patent for someone if they know that you either have an I.D. to make a company or that you’ve already got a partner with the company who’s interested in your invention.

So, I think they encourage that. But then you do have to license it and the university could. It’s like any negotiation for any piece of property, like buying a house or a piece of land. The negotiation could break down.

They can give you a bad deal, or you could be entrenched into the university, and they don’t have to. You know, it’s like any property. They don’t have to give it to you. They could give it to someone.

They could have an exclusive right over here and then no one else can have it. But normally, universities like to have multiple licenses because it gives them more money. At the end of the day, the more money that comes in, the more they can do with other investigators and other patents.

So, it always just depends on what you want to negotiate for. You know, at a certain number of revenue that some things kick in or a certain volume of sales that you can, everything’s negotiable. But the university that is the caveat is that if they own it, they own it, and you have to negotiate with them

. one distinction is Cornell Tech is where the tech school is. It’s and also just in New York City. On Roosevelt Island, they allow fully transferable IP, even though they’ll file it for you. Like, for example, Biotia. We can take a look at it.

We found when we spun the lab out of Cornell Tech, and it’s allowing a fully transferable IP to the company to then be selected. The company got sold and exit, which is very unusual, but it’s very progressive for Cornell Tech to do this to allow you to bring that fully bring IP, not just the license, but actually

take it with you. So that’s the only place I’ve seen that done before. So. But it is possible to do.

That’s cool. And how much? So, the question sort of sort of how much development is needed to get into this market, like, is a patent enough? Do you need a patent to go in? Like is it required? It’s not a question I get sometimes is how much IP protection do you need?

This trade secret.

Off.

Where it’s as various kinds of IP, there’s patents which most people know about, but there’s also just trade secrets. It’s up as a form of intellectual property. It’s obviously less clear what it is when you have a trade secret.

But Coca-Cola has a trade secret like no one actually knows the coke form, except for a few people that originally were sniffing cocaine. But now they just have a lot of sugar water. But you know, it was originally cocaine.

in Coca-Cola. So, there’s ways you can have a, you know, something that’s widely used, but no one knows exactly you have. And you know that that is a form of IP.

And one of the reasons I kind of asked that is because a lot of people don’t realize you don’t have to have a patent to start a company. You can start a company doing PCR for people like you can start a company selling pencils you can say you don’t need, you know, like there’s a lot of things

you buy from companies with Qiagen and like a lot of them, don’t have IP on them. And so, you don’t actually think about it as just like all patents. But it’s really about invention and developing technology and moving the space forward.

OK, let me get one more. OK? This is a good that’s actually will be we’re running off a time. This would be a good closer. How do you educate the public on this space? Like, you know, yeah, microbiome space is full of sort of fact and fiction mixed together, and it’s super tempting to get caught away, caught

in like the just the hype of the microbiome and overselling the microbiome. You know this ball and how do you keep it, keep it grounded in reality, but at the same time, interesting.

I do. Yeah. And you know, I myself, I think everyone, it’s easy to get excited because there’s so much you can discover so quickly for the microbiome and research and clinical approaches. But it’s like any bit of science.

It’s anchored on reproducibility and independent validation of whatever you think you’re seeing. So, you know, the placental microbiome is a great example of what people think. They see some things, but if it’s not replicating how sure that it’s real.

And I think you have to temper your enthusiasm with really good controls, positive negative controls like any experiment and independent validation of it. So, I think, you know, it’s not like you need any magic. It’s the same principles of good science in any field is just replication and independent confirmation.

You know, intra and inter lab validation and that lets you know that it’s real. And so, I think, I guess and using multiple methods to assay whatever your question is, which is also important for way to confirm what you think you’re seeing.

But we’ve published a lot of paper showing that depending on what tool you use, you get very different results for metagenomics processing or how you clean up the sample. How you fragment the sample is well known biases at every stage of collection, analysis, processing and interpretation.

So, you just do it many ways and make sure you keep getting the same answer.

Is there any? Just to close out? Is there anything that you want to tell? The audience like about the space and about startups and whatnot. You know, I can’t see who’s this, but it’s all like. So, is there anything you want to tell people a piece of advice?

Some sage wisdom?

I would say, you know, be pretty, you know, definitely file as many patents you can if you’re in grad school already said that, but I’d say be pretty fearless because you might think, oh, someone else must know the answer to this, but a lot of times no one knows the answer.

So, I would say be a little bit fearless and jump right in because there’s still so much that we don’t know, especially in the microbiome space, that you should jump in, and you can start a company with not with just an idea and a little bit of cash.

And many people did that during COVID. They just sold PCR tests that were already on the market and now they have a ton of money. So, you don’t need, you know, IP or that’s unique for a company that does help long term.

But you know, but the world needs a lot more people innovating on these ideas that bring things to market whenever you can.

Awesome. Yeah, definitely. Startup is very courage dependent and whatnot. So, thank you for coming, Chris. You will also be as a recipient of one of these amazing DNA socks.

They are fabulous. They’re very.

Good. The real prize. And I’m going to give one away right now to somebody in the audience. And that person is that person is Elizabeth Stewart. So, get in touch with Kayla afterwards. Chris, thanks again. We’re now going to go to our panel, and it’s been it’s going to be moderated by Dr. Kiki Sanford from

This Week in Science. And stay tuned and reach out to us if you have any questions and I’m going to give away more stocks at the end.

Thanks. Thanks, Chris.

Thank you. Thanks, Chris.

Next up, we are going to move along to our panel. So, I want to introduce our panel moderator, Dr. Kiki Sanford. Kiki is the vice president of public relations at Science Talk. She is the owner of Broader Impact Productions, and she is the host of the This Week in Science podcast, which I highly recommend and will

link in the messages. So, she’s going to introduce our panelists, and there will be another question-and-answer session at the end. So let me add them. OK, over to you, Kiki.

Thanks, Kayla. Oh, I just want to say thank you to Ivan and Phase Genomics and s2s PR for inviting me to be a moderator for this session. I am excited to be able to talk with all of these CEOs, founders, amazing scientists interested in exploring, launching and growing a startup in the human microbiome space for all

of us today. So, we are joined today by three founders who I will introduce right now. Colleen Cutcliffe is the CEO and co-founder of Pendulum Therapeutics. This is a company developing microbiome targeted medical probiotics. Nick Greenfield is head of microbiome at Invitae, the medical genetic testing company that acquired the company.

Nick founded the microbial genomics and bioinformatics platform one Codex. And finally, but. Not least at all, just the last on the list, Momo Vuyisich, which is the founder and chief science officer for Viome which describes itself as the world’s first and only at home m RNA test for precision nutrition, scanning gene expression to provide health and

nutrition insights. Each of these founders has a fascinating background and has taken different paths to getting where they are today, and hopefully we will be able to dig into what they’ve done, how they got there. And welcome to all of you for joining us today for this conversation and this panel.

first, I want to ask, Colleen, can you give us a little background, what was it that pushed you from what you were doing, a Ph.D. in biochemistry, having moved on to a postdoc and then into research in industry?

What pushed you into starting and founding your own company?

Well, thanks for having me on the panel discussions. Super excited to get to be alongside Momo and Nick. I haven’t seen anybody in years, but good to see you guys, at least on the screen. So, for me, when we decided to start this company, I was working at a DNA sequencing instrument company that had gone public, and

there was just a kind of fundamental new science around the microbiome that was in academia at that time. And it felt like the moment was right to be able to translate all that great academic work into products and at the heart of being able to identify novel products in the microbiome was DNA sequencing technologies and the ability

to analyze them. And of course, that was eight or nine years ago. We’ve come a long way since then and all the additional tools and technologies around understanding the microbiome. But at that time, it felt like me and my two co-founders had a leg up on really understanding how to use DNA sequencing.

And then at a personal level, as I started learning more about the microbiome, I realized that my older daughter had potentially some microbiome deficiencies of her own. So, she was born almost two months premature. And when you have a baby born that early, you get to see them for a couple of seconds, and they get taken away

from you to intensive care, which is where she spent the first month of her life hooked up to all these machines and monitors and receiving multiple doses of antibiotics. Not because she had an infection, but because that’s prophylactic.

They’re so fragile, they want to make sure they don’t get an infection. And around the time that we were starting this company, this publication came out that where they studied 12,000 children and saw that infants who had been systematically exposed to antibiotics below six months of age were also systematically more prone to obesity and diabetes as they

got older. And the Mayo Clinic recently repeated this where they showed that kids who are under two years old and have been systematically exposed to antibiotics were more prone to diseases later in life. Not just obesity and diabetes, but also things like celiac disease, ADHD.

And so, my own daughter was experiencing metabolism issues, and she was in elementary school at that time. And so, for me, I realized we had this technological advantage. We could create products that could help millions of people, including my own daughter.

And the microbiome is a very special opportunity because it allows you to create products that have potentially the efficacy of a drug, but the safety of a probiotic. And that’s really the promise of the microbiome. We’re all trying to realize.

That personal angle, too. There are so many of us who are wondering, you know, how we can, how we can use our personal ecosystem to our benefit and Momo. You also have taken a path from academia to research working at Los Alamos National Labs and into this startup industry.

Can you talk about what led you to make the jump?

I was really driven. I developed some kind of an early onset arthritis, ankylosing spondylitis, autoimmune. No one really knew what it was, but I was suffering for just over a decade, and I was able to cure myself with a diet switch.

It was all science based, and it’s a long story, but I really was entrepreneurial at all times, and I really wanted to use my scientific skills to improve humanity and not just published papers in an academic setting. And so, I switched my career, and I worked really hard with my awesome team to develop some foundational technologies that

we then I basically did. What Ivan and what was discussed earlier, which is we patented the technologies at my previous institution and then I left, and we license those. And so that’s what we’re using today. So that worked really well.

And yeah, so I really want to apply a systems biology approach to all chronic diseases and cancers and find ways to prevent them instead of to treat them. That’s why I was formed.

That prevention through ongoing health and nutrition being a huge aspect of that for sure. And yeah, and nick, from your perspective, you’ve taken a little bit different path to get to where you are getting Master of Arts in environmental based sciences.

And yeah, but environmental.

Studies actually on.

Environmental.

Studies, the.

Science interloper here.

Yeah, please tell that story.

Well, the. I mean, it’s almost a cliche that the story is that I was having a beer on New Year’s Eve with a friend and an M.D., Ph.D., program early like nine. And there was a there was a competition sponsored by an agency called the Defense Threat Reduction Agency, or Vitra, which one of the functions that they

perform as they kind of act as the CDC for the Defense Department. They also run a series of overseas labs, and they’re really interested in weird infections that, you know, military personnel and others get out and they’re also interested in biodefense.

So, they were running this competition for better metagenomics algorithms in 2013. I didn’t know what metagenomics was on New Year’s Eve 2012, but by kind of mid-January, my friend had convinced me to dive in headlong because I knew about software and contests, and he knew about genomics.

And so… really my background is more in thinking about scientific data and data at scale and software, and we approach the problem algorithmically built some cool early technology that we found really intellectually compelling and then put a little demo together that we thought folks would say like, Oh, the algorithms so accurate or oh, the algorithm so

fast. And it was a crummy demo like a really crummy, ugly experience. And we put it on Twitter as one is wanting to do. And folks said, oh, this is so easy to use. And that was kind of that was in maybe March or April of 2014.

And that was kind of the aha moment of we thought we’d built a really cool piece of really cool piece of computational biology software with some data structures and other very low-level details. And then we put a really crude web interface in front of it, and people said that’s really compelling and useful.

And I think at the time, it’s probably still too early. But at the time, you know, there were MySEQ’s landing and state public health laboratories and kind of more and more groups outside of a few of the core kind of early Pioneer Labs were starting to do microbiome.

And so, I think, you know, there was this real need to. Help more applied scientists or folks who aren’t kind of computational, we focused access and make sense of some of this data, and that was kind of the genesis of what became one codex and how we got into the space and obviously dry side perspective

and bias. But yeah, we were a bunch of data weenies, basically.

I like the science, the science for scientists, the data, the bioinformatics side of it. Can you talk a bit about creating a startup that was kind of for scientists that and now it’s been taken up by Invitae and is more public medical facing?

But the startup part of it was it just primarily like, oh, we’re putting it out there for the scientific community to access and use?

Yeah. Well, it’s a good question. So, we did a lot of that. I think if anyone in the audience is thinking about software startups, for scientists, it’s a very hard thing to sell because, you know, unfortunately. Well, I don’t know.

Scientists don’t really like paying for software as a general rule, and there’s a lot of, I guess, under accounted for labor and academic institutions that that can be used in lieu of paying for third party services and science and software in particular.

So, we didn’t really focus on selling to that academic scientific market. We really… our core business was and remains actually, at Invitae be focused on helping biopharma groups, folks doing live biotherapeutics development and otherwise interested in the role of interactions between microbiome and other life, by therapeutics or other therapeutics.

To more systematically understand who’s there in these samples, where the different bugs that are present, as well as what’s going on. So, so we always thought of ourselves as building tools to enable greater velocity of either therapeutic discovery or assay development.

And I think that in Invitae, actually, we’re really supporting both that as well as internally. We’re now obviously at a diagnostics company interested in the microbiome as a source of biomarkers for diagnostics. And the software is really, and data infrastructure is really about supporting that effort at scale and with a certain amount of velocity so that

it can be, you know, so hopefully we can get there and find something interesting and bring something into the world that improves then impacts patients’ lives.

Yeah, thank you. And Momo, your company, you’ve gotten into Nordstrom stores at Bloomingdales, you’re working very highly at the consumer facing interface. So, can you talk about creating a product that is so consumer focused?

I can. So, I do want to intrude with a little bit of an understanding of our company. So, our company recently renamed was renamed to Viome Life Sciences and everything that you can see on Viome dot com. It’s simply one application, just one application of our technology platform, and I am actually on the not on that part

of the company. I’m actually cleaning our Viome health sciences platform. And I want to mention this briefly because I’m really particularly excited about it. The systems biology platform we’ve created. It enables clinical research and large data collection from samples and data analyzes and data science and machine learning.

And this platform has been developed over the last eleven years, both prior at Los Alamos National Lab six years and here at Viome for five years. And the really exciting part about this platform is think of it as the App Store.

So, it’s like a health app store where we provide all the software and the hardware, and anyone can plug into this platform. It’s literally now open to the whole world. So, everything that I have at my disposal, anyone in the whole world can access that 100%.

And so, it’s an open platform where others can build whatever health application is of their interest, whether they want to build a diagnostic device for whatever favorite disease they have or a companion diagnostic device for any drug they’re interested in or look for therapeutic targets.

And so that’s really exciting to me. And then Viacom is just one of the applications we’re building, other applications in cancer diagnostics and vaccines and therapeutics and so on. So, let’s not talk about that one application, Viome dot com. So that is a direct-to-consumer wellness service where consumers provide their stool and blood and soon saliva samples as

well. They actually collect all these at home ship them for our clinical labs, we generate what I call chemistry data. They’re actually metatranscriptomic data, but I call them chemistry and then we overlay mathematical equations. On top of that, those chemistry data to generate personalized food and supplement recommendations for every customer.

And those supplements, they can go purchase them on their own, or they can actually purchase them via subscription from Viome directly. And so, this was basically one of the original ideas as one of the applications of the platform.

And so. Very quickly, we got to work on that, so five months after we started the company, we already offered the stool test and some initial recommendations. And at that time, the recommendations were actually made manually by a large team of people.

So, it was like a team of nutritionists and molecular physiologists and microbial physiologists and some naturopathic doctors. So, it’s really, they would get the data out of the lab, and they would interpret them. But after the initial few months, they actually started teaching all the all our A.I., all the algorithms that they were using for

this. And I started learning from all the data and from our clinical research. And so, about a year and a half later, all everything was replaced by automated algorithms. And then we added the blood test, and now we’re adding the saliva test.

So, we really want to understand it every kind of a chronic disease in sense of systems biology. I’m not sure if you had any specific questions about this.

No, I find it interesting. What I what I was trying to get out was the question of actually producing something that is usable by the consumers and so that the ability of your team, which is multifaceted to be able to interpret your scientific data to create that product, that then is something that, as Ivan asked

earlier, was a question to Chris Mason of, you know, are we not overselling the microbiome to people?

Yeah, I mean, we are just starting. We’re scratching the surface of the tip of the iceberg. So, we’re just starting, but you have to start somewhere. And as long as people don’t make health claims based on, you know, no trials, then that I think it’s OK to start and we are seeing some absolutely phenomenal improvements in some of

our customers and it’s going to get better and better because we’ve created a platform that self-learning. And it’s like a flywheel. And so, for example, one of the fundamental differences between Viome and, let’s say, Quest Laboratories, is that when Quest Laboratories performs 1,000,000th test on a patient, they provide no additional information than from the first test, meaning

they have not learned anything. They simply collect the sample, do the test and report the data. Whereas we use every single additional customer and all the data we get, we use it for machine learning so that every new customer benefits more.

And so, it’s really a self-learning flywheel. So and as we go, we’ll learn more. And right now, you know, I get a I get an email from a customer saying, you know, my psoriasis completely went away, and I’ve been trying to treat it for 40 years.

And they went to Japan, and they went to Bulgaria, and they drink the holy water, and they tried every pharmaceutical and nothing worked. And three months after the Viome diet, their psoriasis went away and they asked me, How the hell did you do this?

And I said, I don’t know. Well, we are not treating psoriasis. We don’t know how to treat psoriasis. But what we’re doing is we’re modulating the microbiome to produce fewer pro-inflammatory signals and to produce more anti-inflammatory signals and just so happens in you.

That was what was the cause of your psoriasis. And we succeeded. But it’s not like a pharmaceutical where you can target a very specific pathway and you can inhibit it, and that was the cause of disease. So, we’re still having to learn a lot and we are only really, we’ve already legally made huge progress in four indications

so far, but we’re going through more.

Great. And, Colleen, your company Pendulum is working in the medical therapeutics industry, but can you talk a bit about how interfacing with the medical community, interfacing with organizations that you need? How do you how do you how do you navigate all of the integrations that need to happen for your company?

Yeah, well, we’re not doing drug development in the way of pharmaceutical would and so we’re selling our products directly to consumers, and I think it’s super important when we’re talking about disease states that the health care community is behind you and you’re continuing to bring them along on the journey because people as much information is available from

Dr. Google. People still do also talk to their actual health care providers. And so, for us, you know, there’s a couple of really important things. The first is that the Mayo Clinic were our first investors and they’ve invested in us at every round.

And I think that that was sort of the beginnings, the foundation of the company and being really clinically and scientifically focused and driven. We have academic partners and clinical partners that we have trials that we’ve been running with, and I think COVID really, really caused us to lose a lot of money on that front.

However, I think it is really important to keep that front and center to Momo’s point. It’s not just about running a trial; it’s continuing to run trials. It’s showing that your product works in different settings and understanding more about where is there a microbiome opportunity and where is there not.

And I think that’s been really important. So, we have educational materials, clinical trial work, medical advisory boards, scientific advisory board, you know, and I always joke that those aren’t just pretty pictures on a website. We actually put all of our advisors to work so.

Chris Mason, who was on earlier, is one of our advisors. We have multiple collaborations together, including through his company, Onegevity. And so, I think those are it’s important to really stick to the science and the medicine so that you aren’t just putting out.

I think somebody wrote earlier shampoo with microbiome in it.

Yeah. Not just sharp shampoo with microbiome, it’s what microbiome, what aspects are you influencing its ecology here we’re talking about? But speaking of systems ecology, as a woman in science and a female CEO, you are. You are a rarity, and I would love it if you could speak to your experiences in in trying to secure funding and

to actually managing a company as a woman and there have been any specific challenges.

Well, I think it’s pretty well established that it’s hard to start a company no matter what. And securing fundraising is hard, I think, and managing teams and growing teams and setting a vision and figuring out when you need a pivot and when you shouldn’t pivot and kind of dig your heels.

And all of those are the challenges of being a founder. And I would say probably for me, the most important thing that I’ve experienced is having co-founders as really important, and I think I don’t know how anybody starts a company by themselves.

But having co-founders that are literally going through the same thing as you or being able to divvy up work or just having someone that you can. Say all the things you’re worried about are nervous about two very openly, it gets harder and harder as the company grows because, you know, there’s not that you don’t want to be

transparent, but there’s just certain fears that you should just keep to yourself. So, I think that having co-founders makes life much easier and much like anything else, just having partnerships and people and a good support network around you helps you be successful.

But I only have an end of one. I’ve never started another company, but I can say, like, it’s ******* hard to raise money. I don’t care who you are.

I think that is just a truism. Put it on a T-shirt and bumper stickers, though. So, we have some questions this half hour. I knew it was going to go by very quickly, but it is just zipping past.

We have some questions from our audience. For those of all of you who have transitioned to industry, McKenzie Lynes is asking How has that transition changed your perspective on science? So, Momo, if you want to start this one.

Well, I kind of had this perspective before I transitioned to industry, I really wanted to do something applied as something that can change people’s lives. So that has remained the same always. I did not, you know, I went to I went to an academic retirement party and the person had published 180 papers and it was

a big To-Do. And it was like, wow, this guy is amazing. He published 180 papers. And I asked, did this that any of these papers impact any humans on this planet in any positive way? And that was a difficult question to answer because they really didn’t.

And so, this is the kind of realization that drove me to exit that academic world where it’s publish proposals, publish proposals, published proposals, just exit that cycle and do something that actually changes people’s lives. And it’s true in industry, you can actually do that.

Yeah, quite true, Colleen.

Yeah, I totally agree, I think being able to point to a population of people and say it changes people’s lives is extremely rewarding and you come in every day. Your goal isn’t around publishing. Your goal is around. How many more people can I help?

And so, if that’s the kind of thing that motivates you, it’s very rewarding to be an industry. I would say the thing that most surprised me when I had my first job in industry coming out of academia because I didn’t work in between my education I just went straight through was that I feel like there was this

perception that if you’re a really good scientist, you’re in academia, you’re a professor. And if you’re like a, you know, second tier scientist or you’re OK, you’re an industry. And I would say that I at my first job, I just kind of walk through the doors thinking that I was going to be a hot shot and

I was definitely not a hot shot. And I think what I. My perspective changed that there are amazing scientists up and down, left and right and industry. And so, if you’re coming out of academia and you only know that one world and you’ve only seen your professors and their colleagues and what that life looks like, I encourage

people to go hang out with some people in industry. See if you can shadow sit in on a lab meeting because I think what you’ll find is that there’s amazing science with just a slightly different perspective that’s going on everywhere.

And I think that was that was important. I just learned it by accident.

Thank you for sharing that. And Nick, did your perspective change?

Well, I don’t I don’t know. I didn’t go through that transition, so yeah.

But you did transition to industries. I mean, you weren’t specifically working in industry.

Yes, I did transition to yes, I transition to microbiome. I mean, I guess I can say a tiny bit about that. But yeah. For me and for the team that we built and now actually the team at Invitae, I think, you know, the reason I got into this space was very much to pursue.

Well, I was in San Francisco, right? There’s a common trope about how there are a lot of brilliant minds being wasted on optimizing ad spend. And I think there’s some truth to that. And, you know, this was a compelling problem through which.

Better software, better data analysis, some of those skills that that I and the team that we built had could, you know, make a difference, whether that’s by accelerating certain therapeutics developments or whether that’s, you know, particular diagnostic opportunities that I think are still a few a little way down the line.

But that we’re actively working towards. And so, I think, you know, finding that was really meaningful for me and really meaningful for the team and kind of that industry transition was really motivated by knowing or having the intuition that that would be there, that kind of meaningful balance of something that was both intellectually engaging but

also had a had a deeper purpose than ads. Not that I worked on ads before or just for the record, but you know, could happen.

If you want more than just clicks, that’s good. And as we get down into the last minute or so, hear from each of you. I’d love to see if you have any words of wisdom for future generations of microbiome startup founders.

If there’s one thing that you could tell yourself before you started, what would you go back and tell yourself? Nick, if you want to start this.

Sure. Well, so I think what Colleen said is true, a lot of things, Colleen said, are true. So, I think it’s very hard to raise money. I think it’s very hard to do. I’m sort of a solo founder and that wasn’t that kind of happened by accident.

And some just like unfortunate context about return to medical school of my co-founder and things like this. I wouldn’t do it that way, like I would strongly recommend not doing it that way. I think having a partner or a couple partners as you get started is really important and really valuable, and I’m particularly stubborn, so I

like managed to get through it. I think being stubborn in general and like not taking no for an answer is an essential quality of a founder and a lot of ways because you’ll go through some valleys or troughs, for sure.

It’s just a question of how deep they are and how regular on the journey. So, I think all those things are true. I think getting great partners is really important. If you can, then if you can’t have those people as co-founders having them as your early team, it’s really important.

And then I guess the other thing I would say is. I think that people often. Think that despite the responsibility and burden of the startup resting on the founders’ shoulders, which it often does a particularly in relationships with investors, I think sometimes there’s an incredible community of folks who’ve built companies or done similarly entrepreneurial things that

I think are there for folks to reach out to and are happy to give back and kind of pay it forward. You know, so I would also say finding folks who’ve been in your shoes or the path that you hope to walk can be hugely helpful.

And, you know, speaking for myself, like if anyone’s doing anything and microbiome on the bio side, I’m always happy to chat and I think a lot of people are.

Momo, would you like to chime in here?

Yeah, I have a couple of actually suggestions. one is that to me, I think while thinking of, say, an academic position or any kind of a position where you have a job and you’re not actually a founder, well, that seems to be less risky.

And people say, 00, founding a company, a company is too risky. I would actually turn that around and say that it’s actually far riskier to have that cushy job because it’s going to prevent you from reaching your maximum potential.

It’s going to slow you down over time. And you’re basically you already know what you’re risking. You’re risking making big progress. You already are setting yourself on a path. Right? Whereas if you become an entrepreneur, you may have failures.

I mean, you guys saw Chris Mason had a failure early on and look at what he’s doing today, right? So, you may have failures. You may have these valleys where you may feel like you made a mistake, but as long as you keep learning and growing, you will eventually come out a winner.

So that to me is a is really the perception that I think is wrong among most people to think that it’s risky to do a startup. I think it’s the opposite. So that’s one thing. And the other thing that I want to mention is it’s the people, it’s the people who you co-found with.

It’s the people who you hire, it’s the partners that you work with. Nothing else matters or everything else to me is just, you know, patents, trade secrets, location, theme. All that stuff is just not important. If you have the right people, you will succeed.

It’s really that simple. And so, pick the right co-founders, the right employees, the right partners, and life is going to be just a blissful success.

You’ll be sitting pretty. And Colin, do you want to finish? Just finish us up here with some advice.

Wow. I really. They took all my ideas. Now I think it’s great advice. I mean, I didn’t get any advice when I started the company. So, it’s kind of like having kids. It’s better to not know what’s about to happen.

I think in addition to all of the awesome ideas here, even though we kind of all very clearly said it’s very hard to fundraise, I think it’s actually really important to try to pick investors that are that are going to be good for you and for the company.

And what that means is like, there’s a tendency to try to alter your pitch to be the thing that you think that investor wants to invest in. And the goal isn’t to get that dollar in the door. That is the immediate goal.

But the goal is to build a company that is going to create the kind of change that you’re envisioning when you start the company. And so, to the point that the moment is all about the people, it’s not just the people in your company, it’s also the investors that you surround yourself with.

And science is hard, and it takes a while to do things. And so having investors that are alongside you for that and aren’t going to pressure you to do things that aren’t really your vision of the company, I think is super important.

It’s hard. It’s a hard thing to do when you’re out trying to get a book to say and also be selective. But I do think it makes a difference to end up with strong investors that are aligned with you.

And the other thing I would say is that expect failure. Failure is just a part of the whole thing. Little failures every day. Larger failures company going under. All of these things are just part of growing and learning.

And if you’re not feeling you’re not really doing something interesting. And so, I think just trying to be not afraid of failure and embracing it, I think is important you’re being courageous if you’re starting a company and failure comes with that.

Yeah, I think scientists, people going through the scientific process are probably well versed in failure, so many experience experiments don’t go anywhere. Your methods don’t work. The protocols are wrong. You have to go back to the drawing board.

So hopefully, you know, this is something that many scientists, graduate students, postdocs are in the process of really getting good at right now to be able to take into their into the world with them. Thank you all of you for this wonderful conversation.

This has been great to get. Get your information. And if anybody in the chat giving comments has questions about specific companies, you can reach out to these individuals separately.

Great. Thank you. Thank you, everyone. I’m just echoing what Kiki said. We really appreciate that as a great panel and yeah, like, thank you for your insights. So, I’m going to go ahead and remove you from the stream.

So, thank you and goodbye. And then we’ll wrap up the event.

Oh, why hello there? Well, thank you guys for staying through all that. That was awesome. Nick, Colleen, Momo, I’ve known you guys for a long time. We worked together, possibly eaten burritos together. But to see you guys all in the panel is like amazing.

I’m very privileged to have you. Dr. Kiki is an awesome moderator. For those of you in the audience. Don’t know. Dr. Typekit runs a podcast called This Week in Science. That is super fun, and I was the guest on it once, and you all should watch it or listen to it.

And they talk about not just genomics. They talk about like space and like fungi that control ants and like that kind of stuff. And so big shout out to that big shout out to our sponsors once again. And the final thing we do at the end is I’m going to give away two more of these babies

and the winners are. McKenzie Lynes and Karl Sabby, you’re going to get an email at the end of this and you’re going to get your very own DNA socks, everybody else. Thank you so much. Follow us on Twitter.

I was about to say smash that subscribe button, but I forgot this is not a Minecraft play video. So, follow us on Twitter. We’re going to have more of these. Send us questions. You know, our goal is to connect you and help you guys do what you need to do.

So, with that, I guess I’ll just sort of stop talking and thank you for coming.

Thank you, everyone. Have a good evening.

Choose This Year’s Metagenomics Award Winner

Congratulations to Dr. Ben Tully on winning this year’s Project ProxiMeta: 2019 Metagenomics Award! Read more about his project, 4. The Complete Hydrothermal Microbial Metal Metabolism

This summer, researchers from across the U.S. sent in short proposals for a chance to win a full-service ProxiMeta™ microbiome workup for a sample of their choice. ProxiMeta combines shotgun metagenomics with in vivo proximity ligation (Hi-C) and necessary bioinformatic tools to help researchers assemble high-quality microbial genomes directly from complex microbiome samples.

 

 

HOW TO VOTE

Each project was assessed by a panel of scientists for scientific merit, novelty, impact, and feasibility, and four finalists were selected. Cast your vote on Twitter for your favorite project.

 


 

THE FINALISTS

1. The Gut Microbiome as a Risk Factor for Arsenic-Induced Cancer

Twitter Name: Gut & As-Induced Cancer

It is estimated that ~200 million people worldwide are exposed to arsenic concentrations exceeding current safety standards. Our collaborators have recently demonstrated that mice and human microbiomes can protect mice from arsenic toxicity. While human stool supplementation fully restores protection to arsenic in germ-free mice, researchers were only able to isolate one microbe, Faecalibacterium prausnitzii, that successfully conferred protection to both parent and infant mice. These results are huge because arsenic poses the highest lifetime risk for developing cancer in humans.We will investigate the role of arsenic-transforming bacteria within the gastrointestinal (GI) microbiome as another possible risk factor.

In nature, arsenic-reducing microorganisms are well known for their ability to generate more toxic arsenic products called arsenites, which are typically formed in anaerobic environments like the gut. Past research indicates that ingested arsenic may also be transformed into the toxic product arsenite by gut microbes thus increasing the risk for the host. On the other hand, arsenite-oxidizing microbes may also provide a benefit to the host by lowering arsenite concentrations. The ability of the microbiome to transform arsenic is determined by its genetic composition, therefore ProxiMeta sequencing technology will allow us to immediately analyze our collaborators rodent stool samples for genetic clues regarding this mysterious protection. Our project goals are to expand on this knowledge by: (1) characterizing the genetic basis for protection to arsenic provided by the microbiome (2) identifying, and then isolating, the bacteria-harboring arsenic transforming genes involved in protection.

We predict that differences in the gut metagenome composition will explain the incidences in arsenic susceptibility within a population or even at the family level. This project will provide important insight regarding how gut microbes contribute to cancer and may lead to novel therapies and probiotics that could target the microbiome of arsenic-exposed individuals.


2. Evaluating Antimicrobial Resistance in Backyard Poultry Environments

Twitter: AMR in Backyard Poultry

Approximately 13 million rural, urban, and suburban US residents reported owning backyard poultry (BYP) in 2014, and interest in BYP ownership is nearly four times that amount. BYP ownership has risen recently due to product quality, public health, ethical, and animal welfare concerns of commercial operations. However, BYP ownership and disease treatment is largely under-regulated, unlike commercial poultry production. Lack of regulation poses public health concerns of transmission of antimicrobial resistant (AMR) bacteria, such as AMR strains of Salmonella, Mycoplasma gallisepticum, and Escherichia coli commonly associated with BYP. BYP owners (2014 survey) were largely uninformed about poultry diseases and treatments but were interested in learning more on disease management.

The combination of a lack of regulation and public information warrants further research into the bacterial communities of BYP and their environments. Cloacal and environmental swabs were collected as part of a 2018 citizen science study where BYP owners reported current and historical poultry antibiotic usage. We propose to conduct shotgun metagenomic sequencing and proximity ligation using the ProxiMeta platform, allowing for increased detection of full-length AMR gene alleles compared to that revealed by short-read sequencing. The combination of PacBio reads with HiC intercontig ligation analysis allows for identification of potential gene transfer events of AMR genes within communities and potential dissemination throughout the environment.

This analysis is especially important considering the public health concerns of AMR persistence in backyard environments. Additionally, investigation of lytic and prophage presence would allow investigation of phage-mediated bacterial regulation that would not be possible with short-read sequencing alone. ProxiMeta analysis of these samples would provide the most comprehensive insight of AMR presences and persistence in BYP environments to date. These findings will be critical for new regulation and disease management for the increasing number of BYP flocks, which currently pose a potential health risk.


3. Unraveling the Metagenomics of Contamination

Twitter: Steel Site Contamination

We propose a metagenome characterization of contaminated Munger Landing sediment located in the St. Louis River, Duluth, MN USA. Seasonal samples are already collected and stored; of which one will be sequenced. Munger landing, is located downstream from the U.S. Steel Superfund site and contaminants include PAHs, dioxins, PCBs, and heavy metals.

Soil condition is integral to high productivity and ecosystem balance at all trophic levels. Human activities erode soil condition through agriculture, mining, sewage outflows and/or chemical/waste disposal into waterways. These practices alter the chemical structure of the soil and break down the microbial community processes responsible for ensuring the balance of biogeochemical cycling patterns in the soil. We hypothesize the activity of these pathways involved in cycling of nitrogen, phosphorus and carbon are altered in contaminated soil systems.

Metagenomic profiling of Munger Landing will provide data to examine microbes, metabolic pathways, and contaminant-processing genes present in the community that can be characterized further using qRTPCR. This project will be presented within a community college microbiology course module. Curriculum utilizing real-world data and the sequencing technology from Phase Genomics will teach students experimental design, troubleshooting, hypothesis testing, data analysis and how to communicate the broader impacts of a study to society, the field of environmental microbiology or conservation.

In the future, this data will assist in designing a longitudinal metagenomic and metatranscriptomic study to assess the ability of remediation to ‘recover’ bacterial community function at the Munger Landing site; slated to start in 2020-2021 as compared to two uncontaminated control sites. Ten sites, slated for remediation, have been identified as having high chemical and heavy metal contamination for the St. Louis River Estuary. The Munger Landing project will establish a workflow that can be applied to other contaminated sites.


4. The Complete Hydrothermal Microbial Metal Metabolism

Twitter: Hydrothermal Microbiome

Hydrothermal vents replenish the oceans with much-needed micronutrients, spewing iron, magnesium, nickel, and other metals from the earth’s crust. These metal micronutrients are used as biological cofactors for organisms throughout the marine food chain. Boiling, sterile hydrothermal fluids quickly cool and are colonized by highly specialized microorganisms that begin to cycle the metal species mixing with the seawater. Though regularly sampled, rarely have hydrothermal plumes been tracked through the water column to establish how microbial colonization occurs through time and space. We lack understanding regarding the replicability of colonization to what extent stochastic processes shape microbial community structure.

While on station at the East Pacific Rise hydrothermal vent field, size-fractionated samples (0.2, 3.0 and 5.0-μm) were collected in the hydrothermal plume emanating from Bio Vent. Samples fluids were collected from the source through the first 1-km of dispersal – the key distance for colonization – and this effort was repeated over the course of 10-days – to determine the replicability of natural colonization events. The application of standard metagenomics sequencing and microbial genome reconstruction through binning would provide novel insight into the cycling of metals within the plume but the use of cross-linked DNA techniques would deliver an unprecedented understanding of how strain diversity impacts colonization and how microbes interact with extrachromosomal elements in the environment.

While some microbes are poised to take advantage of reduced metal species for lithotrophic growth, microbes from the water column that become entrained in the plume will need metal-resistance adaptations to alleviate stress from the elevated metal concentrations present. Metal-resistance genes dispersed through the viral and plasmid pools are essential elements for understanding the functioning of the microbial community in this globally important source of metals to the oceans and effective interpretation of the community can only be achieved through cross-linked DNA metagenomic techniques.

*All finalists projects are owned by verified researchers at U.S. academic institutions.


 

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