Since 2015, Shoreline Biome has developed innovative microbiome sequencing technologies and products from its base in Farmington, Connecticut. Shoreline’s assays have been used in labs across the world to advance microbiome research and provide comprehensive results simply and efficiently. The company’s newest product, the Shoreline Wave kit, is a convenient solution for researchers interested in a streamlined application of Shoreline’s innovative amplicon technology.
Shoreline Biome’s co-founders Tom Jarvie and Mark Driscoll recently sat down to answer questions about Shoreline’s beginnings, the ideas behind the company’s innovative technology, and how it can benefit researchers.
Q: How did Shoreline Biome begin?
Tom: Mark and I were working at 454 Life Sciences, which had been purchased by Roche. We had been talking for years, saying “Wouldn’t it be fun to start a company someday?” We kind of laughed about it. Along the way, we had noticed that 454’s instruments were being used for microbiome analyses and there were a ton of people doing microbiome stuff. We were looking into it, and it seemed like a really great market. We knew what the pain points were and what the product improvements could be. Roche had decided to shut down operations in Connecticut and move to California, so we opted to take our severance and start the company. We just came here to the [University of Connecticut] incubator with ideas of products to make and it was, you know, two guys and a dream sitting in a room.
Mark: But also remember, that was when you called George Weinstock over at The Jackson Laboratory.
Tom: Ahh, yes.
Mark: “Hey George! We’re moving into the neighborhood over there. Want to start a company?” And he said, “Yeah. Absolutely!” That’s what began the collaboration between George’s thought processes and our thought processes. George had ideas about what the product should look like and do.
Tom: Yeah. He was a great early test site, or basically a place we could bounce our ideas off to say, “Is this a good idea?” He would say yes or no, and then we would go back to the drawing board if he said it was a bad idea.
Mark: And that was where part of the work on the lysis came from. George knew back then that the lysis that folks were using was not complete.
Q: What were the early days of Shoreline Biome like?
Mark: We opened on June 15, 2015, but we physically started in our garages and basements.
Tom: When Roche was closing 454, they gave us a year-and-a-half’s notice. It was a good opportunity for us to plan. They put all the freezers, pipettes, PCR hoods, and all that stuff up for auction. We bought some of it, but there were a few things that didn’t sell and they were just going to throw them into the dumpster. For example, the consumables like microfuge tubes—nobody was going to buy those when they didn’t know where they’d been. We knew exactly where they’d been: in 454’s QC lab!
Mark: Tom and I backed up U-Hauls to 454 Life Sciences and took everything that wasn’t nailed down and stored it in our garages. That’s what we moved in here with. We had a bunch of stuff to get us off the ground.
Q: What were your motivations when you started Shoreline Biome?
Tom: Some of it was the classic entrepreneurial thing—you’re just excited about building a company. Both of us were wild-eyed idealists who thought we could make something that people would want and could get to a place where we had products that would allow people to do cool science and make a positive impact.
Mark: Yeah, I agree with that. Having worked with folks in the microbiome field, we knew that we could probably build something that was going to enable a lot of new discovery. Now that we have it on the market, that’s exactly what’s happening. It’s really gratifying.
Q: When you started the company, did you know what the products would be?
Mark: No. We did know that we had to innovate and develop. That’s when we got together with George. The key became that if you wanted to do things with the microbiome, you had to be able to see the microbiome. As a first step, we had to develop this assay so we could actually see what was going on in the microbiome in the strain level. Otherwise, you’re just working in the dark. That became our first product, and not the last one! Because like most science, a good project opens up more questions than answers.
Q: What is your vision for the company? How does it benefit the research community?
Mark: I think it’s a step-wise thing. We know that there are huge, unanswered questions in human health, and it’s clear that the microbiome opens the door to answer many of them. The first step is to ask the questions and see the answers, but then once you start to get that, it opens more doors. Now you can see that [for example] in an infant, there are certain strains of microbes that are starting off in the gut but as they grow and mature it changes over time. Some infants go down a sick path and some go down a healthy path. So, then, how can you make changes downstream? What does a good outcome look like, and how do you more effectively drive a good outcome? So, in all of those things, first you have the discovery part: you discover this good path and this bad path. Now, what do I do to encourage the good path and what do those products look like? You may start with a prototype diagnostic for the good path and the bad path, then you might have a product that would actually push kids down a path you want them to go on. So what’s the vision for the company? It’s to discover new things along the way that enable the development of more new things down the road, such as translational medicine, diagnostics, or perhaps treatment. That’s really the vision.
Q: How are Shoreline Biome products different from others on the market? What’s so special about your products?
Tom: There are a lot of things that are special about them. One is that we set up the products for ease-of-use. People who aren’t genomics or microbiome specialists should be able to get into the field [with Shoreline Biome products], and those who are specialists should have an easy product to use. A big challenge when you have to do a microbiome [study] is that you have to go to one vendor to buy the lysis, another to buy the PCR stuff, and another to get the analysis software and things like that. What we wanted to do was to have a turnkey solution that went from front to back.
Another thing is that a lot of the state-of-the-art, on-the-market stuff is very hands-on and labor intensive. We wanted to develop products that are very simple and time-efficient, and we dropped hands-on time from 10 hours to half an hour. We dropped overall time from 18 hours to 3 hours—that’s a big advantage.
Something else that differentiates us is that we have the ability to lyse—that is, crack open all the bacteria. We have one product that is coming later this year, the Shoreline Breaker, that will lyse all the vegetative cells plus the spores. We also generate high molecular weight DNA in our lysis process.
One final thing: we are really good at small sample volumes. In many other kits, you have to weigh out massive amounts of stool samples—which is a very unpleasant task—but in [Shoreline Biome] kits, you can get away with small inputs. There are a lot of places where small inputs are an advantage, such as in skin samples, microbiomes of individual insects, etc.
The centerpiece of it all is that we’re the only company with a StrainID assay, so that’s the reagents, software, and database that allows us to get strain identification of known and unknown organisms.
Q: How do your products work? What is the workflow?
Mark: Lyse, purify, then amplify. You start with a sample, but you have to crack it open. Our lysis enables you to crack open all of the bugs and then DNA comes out, so we purify the DNA at that point. It’s really simple; it’s done in a 96-well plate with magnetic beads. That lysis-and-purification part comes in one box, and then you have the amplify part that comes in a separate box that gives you two things—a plate with your primers and a 2X PCR mix. You just transfer from your purified DNA into your PCR plate and add your 2X PCR mix and that goes on a PCR machine. For Illumina, when you’re done, you’ll pool those and put them on the sequencer. For PacBio, you’ll pool them and turn that over to your service provider and they will put that in the sequencer. For the analysis part, there’s a lot that is already set up for Illumina so you’ll just do your standard stuff there. For PacBio stuff, we have our own software, the SBAnalyzer with our Athena Database, that spits out a spreadsheet that you can start using to graph data.
Tom: Essentially, we are platform agnostic. We have both Illumina and PacBio products. We really wanted to go for researchers who don’t really know anything about the microbiome but want to put this into their research because it makes sense for them. They can go from sample-in to spreadsheet-out. For samples, we’ve shown that you can put in fecal material from adults and infants, snails, fish, flies, and pretty much any source, but you can also drop in bacterially important samples like gastric tumor tissue, cheese, dirt, and many more. You start with whatever sample it is, follow our workflow, and you’re going to end up with, for StrainID, a piece of software that gives you an Excel spreadsheet that you can plot your results on. So, really, anybody who can handle Excel can get to the end of their data. It really lets the researchers start with a sample and go all the way through to the analysis, without having to know a whole lot of the intermediary steps.
Q: Are there any new products you’d like to tell us about?
Tom: Of course! We have these kits that we call the Shoreline Complete that do all the lysing, purification, and amplification. This is the front-to-back kit, samples-in and pooled DNA ready for sequencing-out. We split those into two kits where we have the lysing and purification, which we are now calling our Shoreline Rapid Prep kit. It’s for people who want to take advantage of our lysis technology, and they can do what they want with the DNA downstream.
Then we have the Shoreline Wave kits. They take the amplification technology that we have, which is designed so that we have primers that are set to cover all of the known bacteria in various databases. Additionally, our PCR design is set up to promote uniform amplification of everything independent of whether it is abundant or very rare.
Coming this summer we have the Shoreline Breaker, which is a kit that uses mechanical lysis. However, the beads it uses are very different from the bead lysis technologies on the market. It provides very uniform lysis of the most fragile vegetative cells all the way up to difficult spores, yielding very high molecular weight DNA.
Of course, we want to mention the SBAnalyzer software and the Athena database that analyzes our PacBio data.
Q: What is the Athena database?
Mark: The Athena database is really part of the entire package. It’s a collection of contiguous 16S-23S gene pairs that contain the sequence between the genes (ITS) so we can get enough sequence diversity to accurately measure taxonomic diversity at the strain level.
In order to take advantage of the StrainID kit, you need a few things. First of all, you need the StrainID amplicon, which we provide as part of the kit. Second, you need to compare those long reads to a database to try to identify those strains. If you don’t have a good database, and one does not exist outside of Shoreline Biome, you’re not going be able to identify those reads on the strain level. We had to go back to the genomic databases and our own data to pull together a database containing all of the strain level information—that is, the contiguous long read amplicon so that we could search against it. The third thing you need is a good software algorithm for doing that comparison. What’s out there right now is all set up for short-reads—and it works great for that—but as soon as you throw long read database and long reads themselves together, you get very poor results unless you modify the software. All three of those—the StrainID amplicon, a good database, and good software—are required. If you only have two of them—say a really good mapping algorithm and the long reads, but you have a poor database—you’re only going to get a certain level of taxonomic differentiation. You really need to have a good database in conjunction with the software algorithms in conjunction with the long amplicon to be able to yield strain level results.
Q: How do your customers benefit from Shoreline products?
Tom: We give our customers a comprehensive view of the microbiome. Our lysis, purification, and amplification technologies ensure that we have a good representation, meaning that what you see in your data is what was in your sample originally. The other thing is the StrainID kits, SBAnalyzer software, and the Athena database give customers a unique view into what’s really going on in the microbiome. It enables them to start doing experiments to see at the strain level and follow strains going from human-to-human in a hospital setting, or for infection control it allows people to start looking at two different strains of a given organism and see that one of them is responsible for inflammation for a given disease because the other one, even though it is the same genus and species, is not a pro-inflammatory organism and it allows a different level of scientific questions and answers.
Q: Why study the microbiome?
Mark: Humans are really a composite organism. We’re not just human cells. We’re actually host to about ten times more microbial cells than human cells. In addition, the genetics of the microbiome is 100 times more diverse than the human genome. If you were looking into human genetics, human genetic problems, diseases, and health, it might make sense to look into where most of the cells are, and that’s the microbiome. Most of the genetics occurring in humans are happening in those microbes. Being able to see this for the first time has opened a window into human health and disease that you really can’t see without studying the microbiome. This is becoming apparent where some of our collaborators who are looking at host genetics—that is, in humans or model organisms—have not been able to see causes of disease or chronic syndromes. But when they look at the microbial component of those organisms, suddenly they are able to see differences that they can follow up with that make sense and also explain what’s going on with these various diseases.
Q: What’s new in the industry, and how is Shoreline addressing it?
Mark: It’s really driving towards strain level of bacterial identification, because people have been working at viewing [the microbiome] at the “thirty-thousand foot level”—at the family or phylum level— and seeing that there are measurable differences. However, they’ve been unable to question which species or strains are responsible for these differences. To ask the next level of questions, people are now driving towards strains. This is where we’re uniquely positioned to see that information: we get real answers to these questions, rather than simply observing trends. Now you can dig in and say, for example, that this bacterium is responsible for resistance to sepsis, and what does that mean? Can we knock in or knock out this bacterium? What effects does it have? What does it produce in its genome that is causing the protective effect, and can we see or develop small molecules? How does antibiotic treatment influence this? There are all sorts of follow-up hypotheses that you can immediately see driving to the strain level, which is why, I think, it is the next step in the field.
Q: What is a recent challenge that Shoreline has overcome?
Mark: Every day is a challenge! Whenever you develop a product, you have theories about what people are willing to buy. Very recently, we started selling product on the market. We discovered that yes, people are willing to buy [our products]. The next question was, “Will they like it and buy it again”? Again, the answer is yes. Getting our products to market and discovering that the market is there is a challenge that we have successfully overcome. The question became, will the science be as amazing as you think it’s going to be? The answer to that appears to be yes as well. We have posters out with some of our collaborators that are just absolutely fascinating in terms of what they’re finding and what the next steps are in their research. These posters are developing into publications as we speak.
Tom: The challenge of going from the R&D phase to the commercial phase is not as easy as everyone thinks.
Mark: The challenges that Tom and I faced when we were running an R&D organization did not require exterior-facing folks. Now that we have a successful product, it’s setting [the company] up so that we have tremendous people in areas like technical support and sales. We brought in a new CEO, Bill McKenzie, to help us establish a global distribution network. The challenges associated with success and growth… if you handle that the wrong way, it can turn out to be disaster.
Q: What’s in the future for Shoreline Biome?
Tom: The microbiome is on the cusp of going from research to applied in translational medicine, diagnostics, and therapeutics markets. We’re seeing that right now, and we feel like our products will be very much in play and well-positioned in these markets in the future. We think that they’ll be used by pharmaceutical and biotech companies to enable them to conduct clinical trials and build products that are going to be the next wave of therapeutics.
Characterizing the human microbiome and analyzing its role in human health and disease are priority goals for researchers around the world. Shoreline Biome accelerates breakthroughs in microbiome research by developing transformative discovery tools that characterize microbiome populations down to the strain level. With Shoreline Biome products, all it takes is three easy steps: lyse, purify, and amplify. Shoreline Biome’s easy-to-use companion analysis software and comprehensive reference database enables straightforward strain-level identification and quantitation of all bacteria in the sample.