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Helena de Puig on Rapidly Sensing Proteins with Project Sparkle

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. 

After watching Formula 1 racing when she was younger, Helena de Puig was inspired to become an engineer and build the fastest car in the world. Though she now focuses on synthetic biology instead of mechanical engineering, her need for speed led her to develop an almost instantaneous sensor for proteins using conditionally fluorescent amino acids that “sparkle” when they bind to the target molecule. Learn more about Helena and her work in this month’s Humans of the Wyss.

What are you working on?

Helena de Puig on Rapidly Sensing Proteins with Project Sparkle
Helena de Puig, Postdoctoral Fellow. Credit: Wyss Institute at Harvard University

During my time at the Wyss, I’ve worked on several diagnostics projects as part of Jim Collins’ Lab. I’m currently most involved in Project Sparkle, where we’ve developed an almost instantaneous sensor for proteins. Basically, we have these small proteins with one amino acid that’s conditionally fluorescent, and only “lights up” when it binds to the target molecule.

What real-world problem does this solve?

Current technologies that identify proteins from small samples take a lot of time, require multiple steps in the lab, and are prone to error. Sparkle’s almost-instant results mean there are numerous applications for our innovation in research and diagnostics.

This is such a powerful technology and there’s nothing like it.

Helena de Puig
Helena de Puig on Rapidly Sensing Proteins with Project Sparkle
Helena and members of the Project Sparkle team after they won the Audience Choice Award at the MIT 100K Pitch Competition. Credit: MIT 100K

I’ll give an example of an application that we presented in the MIT 100K Pitch Competition, where we won the Audience Choice Award – breast cancer diagnostics. Currently, when surgeons remove cancerous cells from the breast, they send the tumor to a lab to see if the margins around it are clear, meaning they extracted the whole thing. This happens after the surgery is complete. In a crazy number of cases, about 1 in 5, they find they didn’t successfully take out the complete tumor the first time. That means they must open the person up a second time and perform another surgery.

Sparkle’s speed solves this problem. Once the tumor is removed, it can be examined while the patient is still on the operating table. If the margins are clear, the surgeon can close the patient up and send them home. If not, they can continue the surgery and remove the rest of the tumor as part of the same operation. This prevents cancer patients from having to undergo multiple surgeries, and saves everybody time, money, and quality of life.  

What inspired you to get into this field?

When I was younger, I decided I wanted to be an engineer because I loved watching Formula 1 racing. I wanted to build the fastest car in the world! When I began studying mechanical engineering, I realized that doing simulations on the computer, spending hours looking at lines and dots that didn’t exist in the real world wasn’t for me. So, I did a minor in materials science. From there I moved to nanotechnology then to biology, to bioengineering, and finally to synthetic biology. As I studied at MIT, I saw all this super cool science that was the future. I wanted to get involved in building the next generation of cutting-edge technologies, which led me to the work I do now.

Why did you want to work at the Wyss?

When I was finishing my Ph.D. on infectious disease diagnostics, a lot of my research ended up intersecting with work coming out of the Collins lab. I started reading his papers, as I also knew that his lab was on the floor below mine at MIT. So, one day, after I presented at my department meeting, I went to his office and told him I wanted to do my postdoc with him. He encouraged me to join at his lab at the Wyss. I’d already heard about the Institute before because representatives from Emulate spoke about Organs-on-Chips in some of my classes during graduate school. So, I was very excited for the opportunity. At first, I got to collaborate with members of Don Ingber’s lab like Pawan Jolly on eRapid and now I am collaborating with members of George Church’s lab.

What continues to motivate you?

Helena de Puig on Rapidly Sensing Proteins with Project Sparkle
The Sparkle Team, from left to right, Subhrajit Rout, Bill Bedell, Helena de Puig, Erkin Kuru, Abigail Reese, Isaac Han, and Allison Flores. Credit: Wyss Institute at Harvard University

For Project Sparkle, our goal is to form a startup. That motivates me on a daily basis because I know that a company will get our technology in the hands of people who can use it, which is the best reason to do the science. Also, having that concrete goal keeps us focused and on schedule.

What excites you about your work?

The team! We’re collaborating with people I never would have met if it wasn’t for the Wyss Institute because our expertise is very dissimilar. For example, Erkin Kuru, from project Sparkle is a biochemist who did his Ph.D. on the conditionally fluorescent molecules that fuel project Sparkle and I never would have thought about using them. The Wyss gives us the flexibility to put our skills together even though we work in different labs and on different topics, and that’s amazing.

We’re collaborating with people I never would have met if it wasn’t for the Wyss Institute because our expertise is very dissimilar. The Wyss gives us the flexibility to put our skills together even though we work in different labs and on different topics, and that’s amazing.

Helena de Puig

The technology itself also excites me. My background is in antibodies and diagnostics assay development, and the fact that we have an assay that gives you a nearly instantaneous readout to detect a protein is super cool. This is such a powerful technology and there’s nothing like it, as far as I know.

What are some of the challenges that you face?

There is a lot to do, and time is limited. For me personally, a challenge is giving up one project to spend more time on another. Technically, the biggest challenge is choosing the right targets to start with so we can expand the platform and get it into people’s hands quickly. To do that, we need to find the best first use case. There are so many cool things we could do, but we need to focus on where this can be most useful in industry and for researchers so we can get it to market.

What is unique about the Wyss? How has that impacted your work?

Helena de Puig on Rapidly Sensing Proteins with Project Sparkle
Helena presented about Project Sparkle at the Wyss Institute Retreat in November 2022. Credit: Wyss Institute at Harvard University

The Wyss is very cool because we have faculty members that are doing some amazing science. It brings together people who want to work with them and want to collaborate. That cooperative atmosphere at the Wyss is the most unique thing we have.

It has impacted my work because so much of it has been multidisciplinary. Everybody is always willing to teach you how to do something or help you, and in turn I have also helped others. It has led to some great collaborative projects.

When you’re not in the lab, how do you like to spend your time?

I see my friends from the Wyss! We like to visit places around Boston. I also try to go running, which is a good sport. I cook a lot too. I love to cook Mediterranean food and Spanish food – I have good recipes for paella, calamari, Basque fish, and other European foods.

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

Helena de Puig on Rapidly Sensing Proteins with Project Sparkle
Helena participating in the final reining Spanish championship, CRN* in Cordoba, 2009, with her horse Gizmo. Credit: Helena de Puig

I used to compete in a horse-riding sport called reining, and I took second place of the non-professionals in the Spanish Championship back in 2009. At that time, I had a horse named Gizmo. Reining is a western riding competition where you guide horses through a precise pattern of exercises like the ones you’d do if you were training the horse to work with cattle. It is a lot of fun and very fast. My favorite part was training to perfect the exercises. Here in the States, I don’t have a horse, but I did try playing polo once.

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

Maybe I’d follow my family tradition and be a lawyer. Or perhaps I’d be a doctor. Or, maybe I’d go with my original idea and build Formula 1 cars.

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?

You feel empowered, like you can change the world, which is really amazing.

Helena de Puig

It’s very cool. Of course, you feel some responsibility, because you don’t want to waste anyone’s time. And sometimes you feel tired because it’s hard work. But you also feel empowered, like you can change the world, which is really amazing.

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