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Nina Donghia on Freeze-Dried Protein Expression

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. 

“I’m always considering the past while I beckon the new age,” says Nina Donghia. Inspired by her forward-thinking grandmother and medically-inclined grandfather, Nina is proud to be doing cutting-edge work on freeze-dried cell-free transcription and translation systems. Outside of the lab, she can be seen wearing vintage clothing, taking photographs with her 1972 Polaroid SX-70.  Learn more about Nina in this month’s Humans of the Wyss.

What are you working on?

My work in Jim Collins’ lab in the Living Cellular Device platform focuses on applications of freeze-dried cell-free transcription and translation systems. This is where we extract all of the cellular machinery that is needed to perform The Central Dogma – the transcription of DNA into RNA and the translation of RNA into protein – and freeze-dry it with instructions to be used as a diagnostic or a therapeutic. In the case of a functional molecular diagnostic circuit, the system is instructed to detect any pathogen-containing nucleic acids, such as viruses, bacteria, or fungi. In therapeutic applications, the system is instructed to express therapeutic proteins of interest, such as vaccines.

What real-world problem does this solve?

The most noteworthy thing about these diagnostic and therapeutic systems is that they don’t need cold storage to work. Every year there are cases where vaccines have to be thrown away because they are sent to places that don’t have the resources to keep them cold. By taking the protein expression processes outside of the cellular context once they’re freeze-dried, we are making them stable at room temperature. That means they can be deployed to the field and other remote locations for diagnostic and therapeutic applications. This marks a huge improvement over the refrigeration-reliant system that’s been around for decades now.

In 2016, the global health crisis caused by the Zika virus propelled us to use our system to create a workflow that could diagnose a patient with Zika, in the field, within 2-3 hours. We have also used our platform to manufacture a diphtheria vaccine on-demand, and to successfully detect Ebola during the outbreak in West Africa in 2014.

Now, we are working to apply the technology as a wearable diagnostic to solve additional public-health problems. For example, we could create lab gowns that have sensors to detect things like drug-resistant staph infections, which have become a very widespread problem in public-health spaces.

The Wyss Institute’s INSPECTR™ technology (formerly known as DROP), enables highly sensitive molecular diagnostic tests that can be performed at room temperature without the need for lab equipment, which could revolutionize a number of fields including medicine, agriculture, environmental monitoring, and more. Credit: Wyss Institute at Harvard University

How has your work been translated?

We knew we had a really great system that worked well in the lab, but we wanted to see it work in the real world. We applied and were accepted as a Wyss Validation Project. Validation Projects are technologies with potential high-impact applications that have successfully progressed through significant concept refinement and meet predefined technical, product development, and intellectual property criteria. We looked at how to address some of the limitations we had while we were developing this system within an academic framework so we could bring it to a clinical or industrial standard. Though the Validation Project pipeline, and because of the type of place the Wyss is and the type of interactions that are forged here as part of daily operations, we were able to really address those limitations and get the work translated in a shorter time frame than any of us could have anticipated. Some of our work was licensed to Sherlock Biosciences as the INSPECTR™ diagnostic tool. The Wyss Institute is such a unique place – without the Translation-focused framework that exists here the licensing deal would not have been possible. There’s really no better place to do this type of work.

The Wyss Institute is such a unique place – without the Translation-focused framework that exists here the licensing deal would not have been possible. There’s really no better place to do this type of work.

Nina Donghia

What inspired you to get into the field?

Nina’s grandfather’s hand-drawn notes on gametogenesis that she found in his comparative zoology textbook.

I have many points of inspiration, all of which stem from my family. I grew up with an identical twin sister, which always had me thinking on the genetic and molecular scale, as well as about gene expression versus gene regulation in a live, real-time example. My mother is an anesthetist nurse, and her hard work and dedication to her field was also a key influence on me.

Further back in my lineage, my grandparents are a big inspiration. One of my grandmothers always wanted to be a scientist. She grew up in the Great Depression and would read stories about Marie Curie. She dreamed of being a selfless woman wearing a white coat, but college was reserved for her brothers. By marrying my grandfather who was a small-town home physician, she was at least able to get into that world a little bit. As a child, I would hear these stories and it definitely inspired me and the work I do here. When I put on my white lab coat, I’m doing that for her.

I’m also doing it for her husband who I never met. I have all of his textbooks from when he was in medical school. One day I was going through his comparative zoology textbook and a piece of paper fell out; it was his hand-drawn notes on gametogenesis (the process by which female and male sex cells divide). Even though I didn’t know my grandfather, and even though he was in medical school before people even knew what DNA was, I know we would have had a lot in common.

What continues to motivate and excite you?

I have always thought of myself as an outsider who has been lucky enough to make my way into projects that are important, where I can make a difference. I see the work I do here as one of those projects. It’s inspiring to be a part of the breakthroughs that are being made every day in this field and to be contributing to work that is already making a positive impact on the world outside of the lab.

I have always thought of myself as an outsider who has been lucky enough to make my way into projects that are important, where I can make a difference.

Nina Donghia

What are some of the challenges that you face?

There are a lot of challenges with protein expression, specifically in vitro protein expression in an acellular context. We are trying to make some kind of protein of interest, but we have to do a lot of research to truly understand our system’s capabilities and constraints. Only then can we edit the system in order to address these limitations and synthesize something that could be impactful.

For example, with our molecular manufacturing paper we really would have liked to have antibodies expressed on demand, but their structure is so complex and there are a lot of post-translational modifications that happen in different compartments of the cell and outside the nucleus. It turned out our ambitions were bigger than what our hands could actually pipette. We were able to pivot, manufacture, and express nanobodies, which are smaller and less complex than antibodies.

How have your work and personal experiences shaped your approach to your work today?

During the six years I worked at the Jackson Laboratory in Bar Harbor, Maine, I also formed a rock band that went on to be somewhat influential. While I obviously still use the technical skills I developed during that time, I have also been able to use my performing and public speaking skills to make the science we do at the Wyss accessible. In this day and age, research is at risk of not being funded because of misinformation, so making these concepts accessible is vital. Communicating my work to the public and talking to students about science is important to me because this type of exposure can inspire students to pursue scientific careers.

When not in the lab, how do you spend your time?

Photographs of Nina and her colleagues in the lab, taken with her Polaroid SX-70.

As I mentioned, I’m a singer in a rock-and-roll band. We put out four records in five years, two of which charted in the top ten of national College Radio charts. These records were critically acclaimed by national and international sources. The band has been on hiatus for a bit, but we’re probably going to work on some new demos soon.

I also enjoy taking photographs with my other grandfather’s Polaroid SX-70, which was the first portable instant Polaroid and was developed in Cambridge, MA. When the Collins Lab wanted to revamp its web presence, I took photos of my colleagues here at the Wyss and at our MIT location to be used on the site. It’s still a work in progress, but I’m excited about how it is turning out. I also take photos of flowers and create digital collages (as pictured on my scarf in the first photo).

I’m always considering the past while I beckon the new age. In the case of this camera, I’m literally looking into the same camera that my grandfather did, but instead of seeing my family members, I see my lab mates who are creating groundbreaking technology.

If you had to choose an entirely different career path, what would it be?

If I had to choose, I believe I would have been good at some form of counseling, maybe genetic counseling or social work. I’d want to do some form of work where one must communicate, collaborate with others, and try to work through some type of problem. Then again, that’s essentially what I do as a scientist.

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’s cool. What we do on a day-to-day basis can seem mundane. We set up experiments, execute experiments, analyze data, and present data. Everything we do is very technical. If you don’t step back and look at the big picture, you can miss the magic. I’m still amazed that I’m in this field and am participating in research that is incredibly impactful and is helping people. In my wildest dreams, I never would have imagined that I’d have the opportunity to work at a place like the Wyss where high-quality interactions and collaborations are part of my everyday life. The fact that this is my reality is pretty amazing and very meaningful to me.

In my wildest dreams, I never would have imagined that I’d have the opportunity to work at a place like the Wyss where high-quality interactions and collaborations are part of my everyday life.

Nina Donghia
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