The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond.
When Nikhil Gopalkrishnan was younger, he loved to read science fiction and fantasy books in his spare time. At the Wyss, he’s turning science fiction into science fact by working on a completely new method of imaging that isn’t dependent on light and can capture or observe things below a microscopic level. Learn more about Nikhil and his work in this month’s Humans of the Wyss.
What project do you typically work on?
I am working in Peng Yin’s lab on a technology called a DNA nanoscope performing a completely new way of capturing an image. First, we measure local distances and code them into DNA molecules. Then, we use DNA sequencing technology to read the DNA, which tells us the distance between the objects. Next, we use an algorithm to reconstruct whatever we are imaging in order to create the final product. The process has a few different names because it’s so new – there are only one or two other labs doing it. I like to call it “imaging by sequencing.”
Our method uses no light and allows us to image things below a microscopic level – within six nanometers of each other. We’d like to use this technique to image things that microscopes cannot capture effectively. For example, we’d like to look at where RNAs are located inside of a cell, because the RNA profile of a cell tells you what a cell is doing.
What real-world problem does “imaging by sequencing” solve?
There are a lot of issues with microscopes that can be solved with “imaging by sequencing.” First, microscopes are cumbersome and expensive machines. With our technique, you have a bunch of chemicals in a tube, which you read using something called a nanopore device that’s the size of a thumb drive. This equipment is far smaller and less costly than super-resolution microscopes.
Another issue is that microscopes only work in certain sample settings. A major reason for that is because microscopes are dependent on light. Since our method is not, we can get into places where light cannot go. For example, if you are trying to look at a sample deep within tissue, you probably cannot get light in there, because light tends to scatter. “Imaging by sequencing” would still work in that case.
A third problem is called drift. Have you ever taken a photo where the subject was moving quickly, or you were a bit shaky, and the image came out blurry? That happens with microscopes a lot. There are tiny vibrations, especially at the nanoscale, and that can cause a blur. With our technique, there’s no camera. You can have things moving or vibrating and you’ll still get a clear, sharp image.
How did you get involved in COVID-19 research at the Wyss?
When the Wyss was ramping-down lab operations, I was about to get on a plane to Switzerland to see my wife. She was in the middle of a six-month placement there for work, so this was one of my planned monthly visits. She and I discussed whether or not I should travel, and in the end, I decided to go. I imagined I’d spend my ten days with her, return to the States, and then return to the Wyss in a month, maybe two at the worst.
Things escalated quickly, and I ended up stuck in Switzerland for a few months. Soon after finding out I had to remain there, I had a virtual coffee with Tom Schaus, a friend and colleague. Of course, we discussed the pandemic, and he told me that a team from the Yin lab, that had already been working on a project where they were trying to detect viruses, had pivoted to targeting the coronavirus when the pandemic hit. I immediately did some background reading and emailed Peng with a few ideas. Peng suggested I come to the next meeting. One meeting turned into many meetings and eventually I became part of the COVID team. It all happened pretty organically.
Can you describe the COVID-19 project you are working on?
We are working to find the viral RNA that causes coronavirus and then develop a point-of-care diagnostic test for coronavirus. The test would be like a pregnancy test. In 10-15 minutes, you would look at a strip and if there is a line, the virus has been detected and if not, then no virus has been detected. Youngeun Kim and Adam Yaseen are leading this project. I’ve been working to support them remotely by attending meetings, analyzing data, doing background research, figuring out the technology landscape, and assisting with whatever else needs to be done.
What keeps you motivated through your COVID-19 work?
Initially, when the pandemic hit, it was so disruptive to everybody’s life. It was disruptive for my life, but of course that was nowhere near the disruption that a lot of other people were feeling. I had this sense of displacement, this feeling that something was not right. The research helped me to get back on track, focus, and feel like I’m doing something useful. Everyone has found ways to cope and feel productive. Some friends are delivering food, some are volunteering, some are reading stories to kids on Facebook Live. I volunteered for the COVID-19 project to keep me from going insane and so I would feel that at least I’m not useless, at least I’m doing something helpful.
Thinking back, what initially inspired you to get into this field?
I don’t think I ever made a conscious decision to be a scientist. I always enjoyed math and science in school, so it was a natural fit. When I was in college, my older brother Manoj was getting his Ph.D. at the University of Southern California, working with this really cool guy named Len Adleman, and he got me an internship in his lab. I loved the experience – the whole process of doing science and thinking about things that way was great. Dr. Adleman is one of the fathers of DNA computing, which is close to DNA nanotechnology, the field I’m in now. I was attracted to the interdisciplinary nature of this field. DNA nanotechnology involves ideas from computer science, where my background lies, and information science, but at the same time there’s chemistry, biology, and physics involved.
What excites you about your work?
It’s exciting to be able to be part of the ideation process with a team of such smart people. When we’re doing science, especially the kind of work that I do, it’s actually very creative. Though I’m not musically inclined, I imagine that when musicians are jamming together, and one does something and another knows how to respond and build off of it, there’s a synergistic connection between them and they feel something. I see science as analogous to that. Somebody starts with an idea and soon you’re bouncing more ideas off of each other. Eventually you land on something that you immediately recognize as a good idea and there’s a connection. There’s this rush when you know you’ve figured something out. That’s the part I really enjoy.
What are some of the challenges that you face?
Things don’t happen as quickly as we want them to. Science is hard. You cannot leap. You have to lay the groundwork and sometimes you’re chipping away at the same problem for years. The gains are usually very incremental. It’s rare that you’ll make a big jump. The hardest part is staying motivated during those periods where things feel like they’re going slowly.
If you had to choose an entirely different career path, what would it be?
It’s hard because so much of my life is centered around science! I think maybe if I wasn’t doing this I would have gone into teaching, because another thing I really enjoy is communicating. While my favorite thing about science is the ideation process, I’m also passionate about science communication. I think it’s so important and not a lot of scientists spend time doing it. Teaching would allow me to explore that.
How have your previous experiences shaped your approach to your work today?
Ever since I was a child, I’ve loved to read. When I was a kid, aside from my books for school, I would read mostly science fiction and fantasy novels. Those kinds of stories expand your horizons and your imagination, and I believe they have had an effect on my science. I tend to go towards projects that are more creative. I’ve heard people say that the Wyss turns science fiction into science fact, and that certainly resonates with me.
When we’re not social distancing, what do you like to do in your spare time outside of work?
I love playing sports – I play a lot of cricket. I’m on a team here in Boston called the Cavaliers. There’s actually a cricket league in Massachusetts called the Massachusetts State Cricket League, though it’s not active this year since the regular season is April through September.
I also love hiking. While I was stuck in Switzerland at the beginning of the pandemic, I was lucky enough to be able to take some of the most beautiful hikes. I enjoy skiing and have been doing it for ten years now.
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
It feels like a huge privilege. When we’re not in the midst of a pandemic, I come into this building that is so impressive, see the Wyss logo, and then they allow me to work with these super interesting things. There’s a danger that you will forget how privileged you are, but somehow it has never left me. I still find myself thinking about how lucky I am to be working at the Wyss. It’s a really special place. Not only do you have researchers, but you have people to help you communicate, a business development team to help bring your idea to market, and tons of other support that is inspiring and hugely appreciated. You truly get this holistic view of science that I’ve never seen in another lab. I feel incredibly lucky to be allowed to make these contributions here.