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Meet Our Expert Erik Splinter

Meet Our Leader: Erik Splinter

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9 min read

In Meet Our Expert you will get to meet the talented people behind Cergentis' success on a personal level. In this interview, our CTO Erik unpacks his childhood memories, reveals his motivation to embark on a startup journey, unfolds the early beginnings of proximity ligation and connects the dots as to how our proprietary TLA technology came about!

Can you tell us a little bit about your childhood?

I come from a family of 4 brothers and grew up on a farm. My parents no longer have it though, they’re now retired and no one wanted to take over. We all decided to pursue different paths. One brother works in electronics, another one in organizational development and the last one has a role in finance. In terms of childhood memories, I remember spending a lot of time outdoors, building sheds and helping out on the farm. There was always something to do!

Where does your interest in science come from?

It was sort of a stochastic choice! I do remember the moment it happened though. In high school, we could pick the courses we were most interested in. At that point, I dropped all the languages and chose biology, mathematics, and physics. We had the opportunity to visit universities as part of a “career orientation” day. The options that interested me the most were: mechanical engineering, architecture, and biomedical laboratory. There was a speaker for every study major, but I found the one for the biomedical laboratory stream the most interesting and enthusiastic presenter! That motivated me to sign up for a medical biology study at Rotterdam University of Applied Sciences!

How interesting! Had there been different speakers on that day, you might have ended up taking a completely different career path.

There were even more coincidences! During my studies, I had to perform a research internship. At the time, I wanted to learn more about viruses. But it turned out that the group leader I was applying at, did not have the time to provide proper supervision… So, even before starting in that group I was quickly reassigned elsewhere. That turned out to be a silver lining, because I ended up with a great mentor, from whom I was able to learn a lot!

By the end of my internship, Frank Grosveld [Head of the Cell Biology department] asked what my plans were and informed me of available vacancies. While I was lucky to have received 6 or 7 other offers, I chose to work with Wouter de Laat as a Research Technician. Back then, Wouter was considered as the “new kid on the block” with great potential. He had just received his first grant and was busy building his first team. I was actually the second one to join his group and remember working on this “funny” beta globin locus trying to figure out how gene regulation was done on this locus!

What made you decide to eventually embark on a PhD journey?

In science, and more specifically in academia, there are only a couple of permanent positions available. As a Research Technician, I was at some point one of the lucky few who managed to secure a permanent contract. From a career perspective, I was “set” and would, had I stayed, continued in that same role for the next 40 years. So, essentially, within 4 or 5 years into my career, I had reached the “highest point” at my level. Next to that, I would see this cycle of PhD students coming in and out. It was always great to see them start and a lot of fun to see them grow, but as soon they were done [with their studies], they’d leave, and a new batch of students would come in. At some point, I also felt that I had mastered the techniques we were using in the lab, be it Southern blots, PCR, cloning. I knew the “tricks” and could keep performing them over and over again, teach them to others but that would leave little room for personal challenge or growth. Instead, I wanted to see if I could take the projects that I had already embarked on to the next level by getting myself into a PhD trajectory.

How involved were you in the discovery of the TLA technology?

Actually, the idea of these proximity ligations was opted very early on, I think half a year or so into my first job. Someone in the lab back then had tried it but eventually dropped the project. Then, a Science article from Job Dekker et al. came out, showing that it works in yeast. That motivated us to leverage this “tool” to find out how the beta globin locus is regulated. Therefore, I ended being the first one pipetting those 3C experiments as well as doing the first proximity ligation experiments! We later found out that this indeed works and that there was looping. However, at that point, we had only performed 2 experiments and therefore, had only thin evidence to present...

Shortly after, Wouter and Frank went to a conference, where a competitor presented his team’s data and explained how they could do looping using a very different method known as: RNA trap. A labor-intensive approach that’s also very difficult to reproduce. Nevertheless, they had their manuscript ready and were going to submit to Nature. So, we got in touch with Cell and told them about our story and whether they’d be interested in “scooping” Nature. They were on board, and we had until the end of summer to have our story ready. So, we pipetted all summer long! Everyone knew exactly what to do and would make sure to send the data to Wouter who was in charge of typing the manuscript. By the end of summer, everybody was completely wasted but the manuscript was ready. We then sent it to Cell. Unfortunately, it came back with comments for additional testing, at which point we thought Molecular Cell might accept it as it is. Indeed, it got through but one month after our competitor had published their story in Nature... However, to this day, whenever scientists refer to looping, they typically refer to our paper.

When did the idea of spinning this tool off into a company came about?

Over time, the technology evolved. From 3C to 4C, where we started getting peaks, or coverage, surrounding the primer set. This was around 2004 or 2005, and for us that was very annoying because it made data analysis very difficult. But it’s not a bug, it's a feature, which allowed to reveal whether the structure of the DNA was in order. A feature that’d have value in case of diseases, where the structure is interrupted. Cancer for example.

Wouter realized that and had discussions with the department of Clinical Diagnostics at Erasmus University Medical Center. This led to a collaboration which ultimately yielded a paper in 2006 from Marieke Simonis et al., showing the first proof-of-concept.

Around that time, there was a realization that this technology might be useful in the clinics. To check whether this tool could actually be commercialized, Wouter got in touch with Max van Min (co-founder and CSO) who had a consultancy firm at that time. Although they saw potential, they also felt that the technology gave too sparse information. In order words, despite the fact that this 4C technology could uncover translocation events, it couldn’t really yield every single nucleotide “underneath” them. In trying to improve this, TLA technology was born, which was a new flavor of a proximity ligation technology.

The IP was filed and we got startup grants assigned to the Hubrecht Institute, where Wouter’s lab migrated to in the meantime. With this money, we worked on building the proof-of-concept article.

Around that time, I was also finishing up my PhD. A month or so before that, I was actually looking for a postdoc and had found 3 positions. I was planning to move abroad. But with this capital to start Cergentis, I was asked to join the company and therefore, also had this as an option to consider. Until then, I had seen just a single experiment by Paula de Vree, showing some proof-of-concept. We were all still a bit “skeptical” that this would work because there were a lot of different issues that we could run into. But Paula was able to get some spikes of coverage flanking the location of the primer set. So, I thought: “let’s jump on this adventure and see if we can take Cergentis off the ground!”. The idea of figuring out how we could best optimize this new technology and how we could bring it to the patients and improve diagnosis motivated me very much.

How did you experience joining a startup?

For me, it was a very exciting challenge! My only connection to Cergentis at that point was the technology itself, which I was already working on and helping optimize for 8 or 9 years. Taking it one step further and finding a tangible application and market was entirely new to me. I just had to do it! It was irresistible!

Obviously, the learning curve there was very steep as I became a group leader “overnight” and had to organize a lot of different things. At the beginning, I was still helping out in the lab. But eventually, as the company grew, I found myself sitting more and more behind the computer, taking care of emails, carrying out meetings and so on. It’s rather ironic, because I remember telling myself - when I was still a Research Technician and seeing Wouter sitting behind his desk all day, writing grants and sending out emails - that if that would ever happen to me, I’d kill myself! [laughs].

2022 is a special year for Cergentis because we're celebrating our 10-year anniversary! Can you weigh in on some of your personal favorite milestones?

Well there’s this whole gradual growth process that Cergentis went through. At the beginning you have “nothing” besides the technique and the promise. Then all of a sudden, you get customers who are willing to give it a try. Cergentis was founded with the aim to bring the technology to the clinic. So, we started knocking on hospital clinical lab doors to introduce our technology and would try to convince them to adopt it. As promising as our technology sounded, they wanted to see more data, which we didn’t have... In hindsight, we weren’t ready at all! So, we went back to the whiteboard and tried to figure out other applications. We noticed its real potential for transgene integration site mapping for Chinese hamster ovary (CHO) cells quality control. Which to this day, still represents the core of our business and the bulk of our revenue.

We still had the desire to move our technology into the clinic. 2018 proved to be a turning point as we were awarded the Horizon 2020 grant. It’s important to note that until that point, Cergentis’ growth was entirely organic. Therefore, we had to be strategic in the way we were going to spend that money. But having access to this prestigious Horizon grant allowed us to hire more people and put more focus on R&D. That project turned out to be successful and culminated in the FFPE-TLC technology, published in Nature Communications in 2021. That was a major joint effort, together with researchers from Hubrecht Institute and lymphoma experts from 5 different Dutch pathology labs (University Medical Center Utrecht, Amsterdam Medical Center, University Medical Center Groningen, Leiden University Medical Center and Laboratory Pathology East Netherlands (LabPON)), where we demonstrated the added value of our proprietary technology on degraded clinical samples.

I also have to say that having the chance to have Jan Dekker and then Joris Schuurmans as our CEO, allowed us to further focus the company’s goals. Without their leadership, experience, and vision, we would have not been able to have Solvias acquire us!

Can you tell us a little more about our recent acquisition by Solvias?

First of all, I think this is a major achievement for Cergentis. It’s a true recognition of our ability to deliver high-quality services to our customers. In my opinion, this acquisition will definitely allow to speed things up for both of our customers, as Solvias will be able to offer a suite of high-end analytical solutions that can probe both at the genetic and protein level. Our businesses are very much complementary. On top of that, we truly have a shared vision and ambition, and both deeply care about solving our customers’ needs and providing them with meaningful insights and services.

As CTO, how do you manage to always generate new ideas and how do you encourage creative thinking within the team?

I think my role should not be overestimated here! Because our customers have certain needs and specific demands, we are motivated to provide them with the best genetic QC solutions to these challenges. On that note, we’ve recently offered a new add-on digital droplet PCR for our customers, which allows quantitative copy number determination.

At the end of the day, R&D is very much a team effort! Everyone regularly meets up, new ideas are exchanged, collected, discussed, and ranked in order of priority. With that said, creativity is very handy to have because the issues we’re trying to solve are rather challenging and therefore, this requires creative solutions.

At the moment, we’re focused on “polishing” the capabilities of our technology, to make our solutions even better, to figure out how we can continue serving our clients better, and to find out if there might be any other applications that could benefit from our proprietary assays.

Outside working hours, what are your favorite hobbies?

I like to cycle! In fact, I have a race and a mountain bike. So, I spend quite a few hours training, though not enough! That is one of my biggest hobbies.

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