THE IDEA FACTORY
In 2015, Max Wilson, who had recently received his PhD in molecular biology at Princeton University, journeyed back to his alma mater to work in the optogenetics lab of Assistant Professor Jared Toettcher. Optogenetics is the study of genetics and optics, with the purpose of controlling events in specific cells of living tissue. Striving to get to know his fellow lab researchers, Wilson initiated a weekly beer and pizza night. There, they could gather to talk about innovative, nuanced challenges in science. The goal of this event, eventually called the “Idea Factory,” was to refine conceptual ideas into active projects. The Idea Factory “naturally evolved week by week into us questioning the faults … of modern medicine,” Wilson explained.
Gradually, plans for two projects developed. One project would enable researchers to use light-responsive proteins to control the therapeutic behaviors of cells, greatly reducing treatment side effects. The other project focused on using precision medicine (medical care that utilizes genetic or molecular profiling) to target tumor cells and reduce the severe side effects of traditional radiation and chemotherapy. Despite the projects’ ever-changing plans, the work of Wilson, Toettcher, and Alexander Goglia, a student in the Rutgers Robert Wood Johnson Medical School-Princeton University MD/PhD program, ultimately aimed to pinpoint the site where a therapeutic behavior modification occurs. Then, they could customize therapies to specifically target cancerous tumor cells. Toettcher, acknowledging the importance of the “Idea Factory,” remarked, “We always look for a problem that hasn’t yet been solved.” He explained that while scientists can control what happens inside a cell, they cannot yet control what happens to proteins outside it. “We think [this project] could make a big impact on the way that we actually perturb and probe cells for basic scientific research, which will help the academic side [of science] as well,” Toettcher said.
THE JOURNEY TO PRINCETON
Wilson’s original interest in optogenetics derived from a summer he spent learning about the mathematical modeling of cell processes at a computational biology lab at UC San Diego. After this experience, Wilson realized there was nothing he could do to test the models and felt that molecular biology “lacked the types of tools that would be useful when using mathematics to understand how the system works in general.”
Wilson met Toettcher at a Princeton faculty talk about cellular optogenetics. Toettcher shared Wilson’s background in computational biology, as well as his frustrations with the lack of precision in experiments. Toettcher spent his postdoc years building the first generation of optogenetic tools—proteins that could be turned on and off by activity in a living cell. “It didn’t take long before I realized that he was exactly the sort of person who would be great to get this enterprise off the ground,” Toettcher said, describing his first meeting with Wilson. Goglia, the medical student, also found his way to Toettcher in a manner similar to Wilson’s. He found Toettcher’s work fascinating, describing it as focused on a “beautiful, bigger process that really can be applied to development, to studies of how signaling and feedback work within cells.” Before starting medical school, Goglia had worked in a lab where cancer was treated using precise beams of radiation. “In my mind,” Goglia said, “I saw the future of creating an analogous situation for optogenetic therapy, where you have the optogenetics suite and you apply beams of light to treat patients in sort of a similar way.”
As Wilson and Toettcher pointed out, the union of this group—one medical scientist, one MD/PhD student, and another long-term researcher—brought together people with a very complementary set of skills. This skill set led to Wilson earning the New Jersey Health Foundation’s Innovation Grant, worth $50,000. “Our Innovation Grant program is geared specifically to advance translational research projects that demonstrate the potential to offer improved and focused treatments and cures for people affected by a variety of ailments,” Dr. George F. Heinrich, vice chair and CEO of New Jersey Health Foundation, stated. “Dr. Wilson’s projects use innovative approaches that deserve further exploration.”
“It [was] one of the first times that someone in this department received funding from venture capitalists to do science that will result in technological innovation,” said Wilson, reflecting on the award. “It gives us concrete motivation and goals to do applicable translational science in labs at Princeton, which are normally known for doing basic research.” Toettcher shared Wilson’s sentiment, saying, “It is really wonderful, when you are a new lab, to have seed money that allows you to pursue ideas that may be too risky to ask for funding from the National Institutes of Health or the National Science Foundation right away.”
OVERARCHING GOALS OF THE PROJECT
While receiving funding, the project changed to revolve around a singular goal: making drugs more controllable in the body. “If you take a pill of any sort right now, once it goes into your body, doctors completely lose any ability to intervene in the treatment,” Wilson said. As an optogenetics lab, the team is experienced in trying to make proteins responsive to different wavelengths of light. “We thought that we could engineer light-controllability into an entire class of drugs, which would solve a bunch of different problems that currently exist in medicine,” he said.
The researchers’ ultimate goal is to be able to control exactly when, and for how long, a drug is active in a patient’s body. Wilson described their experimental procedure as “hacking biology,” while Toettcher declared that the team is just as likely to take an iPad and a sauntering iron and build new tools that can stimulate cells using light. “We have built virtually everything we need for this project to run,” Toettcher said, “and that kind of hacking and playing around with new toys is something we all enjoy.”
Toettcher has high hopes for the project, especially since Princeton is currently striving to establish a formal set of resources to help teams like his. He explained Princeton’s new focus on creating a startup company space. In addition to financial resources, there are now places on campus where it is possible for graduate students and postdocs to start their own companies based off of their scientific research. Such resources are important because they provide opportunities for researchers, especially those who do not plan to become professors, to have a tangible impact.
Wilson echoed Toettcher’s sentiment, saying that in biology and translational medicine, the time it takes to turn a lab finding into a drug is often referred to as “the valley of death.” “Princeton is now making all these resources [available] to cross that chasm more smoothly. It’s a huge advantage,” he said. In the future, the team will continue to conquer chasms one by one, furthering the field of optogenetics and creating innovative technologies to impact generations to come.