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Ninning Liu on DNA Barcoding

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 Ninning Liu started his work-study job in college as a research assistant, he discovered a love for microscopy. At the time, he thought a good microscope image was about as close to an unambiguous answer as you could get in biology. But what if you could get information about biological function and form from the same image? Now, Ninning and his team are exploring that possibility with their generalized DNA barcoding technology platform. Learn more about Ninning and his work in this month’s Humans of the Wyss.

What are you working on?

Ninning Liu on DNA Barcoding
Ninning Liu, Postdoctoral Fellow. Credit: Wyss Institute at Harvard University

I am working on a Validation Project for a generalized DNA barcoding technology platform with my colleagues Jocelyn Kishi and Sinem Saka. We are developing a robust platform that combines two independently powerful capabilities: microscopy and DNA sequencing. Using a microscope, you can take an image of a cell at a great magnification. This imaging allows you to see very fine details of cells, including cell organelles and cell structures. DNA sequencing allows you to read the letters of the genomic DNA, or to read the mRNA transcripts that a cell produces. Sequencing capabilities are especially important for the mRNA transcripts because they are so small and crowded together that it’s very difficult to understand what’s happening from an image alone. Usually, you have to choose to either image or sequence a sample; it’s very hard to do both. If you could, that would be the best of both worlds – you’d have a clear picture, which is always useful in cellular characterization, and you’d also have really detailed sequencing information.

 

By joining what we see with what we sequence, we can better understand the complex biological pathways that give rise to life and also those that lead to disease.

Ninning Liu

Our technology allows you to tag molecules of interest, or barcode them, to gain spatial information and encode that data into cells using DNA. When that information is encoded in a microscope image, you are combining sequencing and imaging data. By joining what we see with what we sequence, we can better understand the complex biological pathways that give rise to life and also those that lead to disease. We are working to bring the throughput, fidelity, and speed that you find in the electronics industry into the process of encoding DNA sequences onto biomolecules.

How can this technology be applied in the real world?

In some sense, because the applications for imaging are so broad, the question is actually what can’t it be used for? The most immediate application is to obtain comprehensive data in drug responses. This will allow us to streamline the drug discovery process. This technology is also highly relevant to digital pathology. For example, pathologists try to identify cancer states when looking at a slide. This technology will allow them to really drill down into the gene expression profile of the tumor by layering sequencing and imaging data.

What inspired you to get into this field?

Ninning Liu on DNA Barcoding
Microscopy has numerous applications, and is a field Ninning has been interested in for some time. He produced this super-resolution image of microtubules created with DNA-PAINT, which coincidentally has the shape of a human face in profile. Credit: Wyss Institute at Harvard University

In middle school, I used to read biographies of famous physicists like Einstein, Gauss, and Newton, and I thought I wanted to be a physicist when I grew up. The interest in science was there from early on. When I started college, I was a biochemistry major because that was the pre-med major and it was the one all of my friends were in. In order to pay for school, I had a work-study job as a research assistant, and I discovered that I really like microscopy. At that time, I thought biology was messy enough and a good microscope image was about as close to an unambiguous answer as we could get. Later on, I realized that when you’re at the cutting-edge of imaging resolution, this is no longer true. Now, I wouldn’t even consider my work to be in the field of microscopy. The best way to describe it would be in its own field of DNA barcoding.

What continues to motivate you?

Thinking about the example that I set for other people and the examples I aspire to keeps me motivated. At some point, people in my life, whether it be my extended family or students at science fairs, started looking up to me as a barometer for what a scientist should be. I might not always deserve it, but it certainly motivates me to keep everything together and set a good example.

In terms of what I aspire to, one of my scientific heroes is Claire Patterson. He led a public health campaign against lead poisoning based on his discoveries, despite immense pressure to abandon it from oil corporations and other lobbies. It was equal parts scientific brilliance and moral courage. Now we cannot even begin to estimate the worth of that campaign for future generations. Seeing what science can do is really motivating.

Ninning Liu on DNA Barcoding
Ninning collaborating with his team member Josie Kishi during the Wyss Retreat in 2019. Credit: Wyss Institute at Harvard

What excites you the most about your work?

Working with an incredible team to cultivate a little corner of the scientific space that we can call our own is very exciting. We’re building projects from the ground up into something that will hopefully be great.

What are some of the challenges that you face?

Right now, the pandemic is front and center in everyone’s lives including my own. It is a huge challenge. I am fortunate enough to have the option of working from home if I need to. As much as I hate being cooped up in the house all day, I know I’m lucky.

Before COVID-19, one of the biggest challenges to overcome, besides equipment costs, was self-doubt. I worried about whether or not this technology would work and whether or not I could optimize it. But, as our team plugged away at it, we reached a point where we had a reasonable expectation of success and I was able to conquer this challenge.

How do other teams across the Wyss Institute support you and your team?

When I first learned about the Wyss, I got hooked just from seeing the incredible science on the website. I thought to myself, this place is crazy – I want some of that! Now that I’ve been here for some time, I see that it’s so much more than that. I can’t emphasize enough how critical people like Jess McDonough, Jay Culverwell, and the entire communications team are to building the IP foundation, public awareness, and networking opportunities needed to deliver a technology to market. These translational aspects of science and technology development that occur further down the pipeline are things I never would have thought about without their help and it has been an enlightening experience.

When I first learned about the Wyss, I got hooked just from seeing the incredible science on the website. I thought to myself, this place is crazy – I want some of that!

Ninning Liu

How have your previous experiences shaped your approach to your work today?

When I started graduate school, I had an aversion to highly popular and competitive areas of science, so I ended up in an obscure field of bacterial DNA motor proteins. While there are huge benefits to working on basic research questions, I realized that past a certain point, the lack of critical outside interest made me too comfortable and caused me to stagnate as a scientist. Through this experience, I learned to try and find the right balance between going off the beaten path but not so much so that I end up off-roading into the wilderness.

When not at the Wyss, and not social distancing, how do you like to spend your time?

Before the pandemic, I really enjoyed spending time with my friends. I am lucky enough to have people from my previous lab and other social circles in both Boston and New York. On the weekends I enjoyed hiking, seeing movies, or going to standup shows. On an almost monthly basis, I’d take a bus to New York to see a Broadway show, go to an escape room, or just visit with friends there. I also enjoy reading sci-fi books, like the Warhammer series and the expanded Star Wars universe.

Ninning Liu on DNA Barcoding
Ninning loves animals, and his alternate career path would involve them somehow. Credit: Ninning Liu

What is something unique about you that someone wouldn’t know from your resume?

I have a set of 1:30 scale miniature cars that I assembled back at my parents’ house. When I was in elementary school, and my teachers would ask me what job I wanted, I would say auto mechanic. My parents’ car often broke down and I wanted to fix it. If I can ever afford a place with a garage, I’d like to get a classic mustang and figure out what it is that people do with full-scale cars in garages.

If you had to choose an entirely different career path today, would it still be a mechanic?

No, it would probably be a something related to animals. I’ve always loved animals and I used to do volunteer work at a dog shelter in Berkeley. I might want to be a zookeeper, specifically one responsible for feeding and training seals. Or maybe I’d like to run a fox orphanage or an animal shelter. Sometimes my friends and I think about wild and possibly unreal jobs we’d enjoy doing. I could be some kind of herb hunter, where I go down to the Amazon and search for undiscovered plants to use for novel pharmaceuticals. Another idea is a koala pararescue, where I’d save koalas from approaching brushfires and care for them until it is safe to release them back into the wild.

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 is an incredible privilege to be working on cutting-edge research, an opportunity that few people have. When I look at all of the infrastructure that goes into simply getting the lights to turn on in a building so that this research can proceed, I feel like I owe it to myself and society to give 100%.

Ninning Liu

It is an incredible privilege to be working on cutting-edge research, an opportunity that few people have. The pandemic has really sharpened my worldview on what is essential. Vaccines, diagnostics, and human health are obviously extremely important, but a city wouldn’t last for even three days if all of the electricians, plumbers, maintenance staff, and other essential workers didn’t do their part. When I look at all of the infrastructure that goes into simply getting the lights to turn on in a building so that research can proceed, I feel like I owe it to myself and society to give 100%.

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