Ph.D. student Stephen Tucker Receives NIH F31 Award to Build Next Generation Microscopes

NYU Tandon Ph.D. student Stephen Tucker is building a high speed microscope to capture neural activity. Now, an F31 fellowship from the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health (NIH) will support his efforts to put that technology to work on a fundamental question in sensory neuroscience.

Tucker, a fourth-year Ph.D. student in Biomedical Engineering, works in Professor Shy Shoham’s Neural Interface Engineering Lab, which is primarily based at NYU Langone and affiliated with NYU Tandon. His research focuses on developing optical tools that allow neuroscientists to observe and manipulate activity in the living brain.

The centerpiece of his doctoral research is a new approach to two-photon microscopy, a form of imaging particularly useful for neuroscience because it can peer hundreds of micrometers into living brain tissue and record the activity of individual cells. Scientists can pair these microscopes with genetically encoded fluorescent sensors that cause neurons to change in brightness as they become active. The result is a video of the brain at work, with individual cells flashing as neural signals move through a region.

But improvements in those fluorescent sensors have created a new engineering challenge. Older sensors commonly measured changes in calcium levels inside neurons, which occur relatively slowly. Newer sensors can directly report changes in a neuron's membrane voltage, providing a much faster view of electrical activity. Capturing those signals requires microscopes that can keep up.

“Typical two-photon microscopes might collect roughly 10 to 60 frames per second — the microscopes have to be much faster,” Tucker says. “What I’m working on is a microscope that can get up to around 500 frames per second. This enables people to do the measurements they’re used to doing with two-photon microscopes, but with a new generation of fluorescent probes that neuroscientists are really interested in.”

His F31 project will use that increased speed to investigate the brain’s olfactory system in a collaborative effort co-supervised by Professor Dmitry Rinberg.

When information about an odor travels from the nose into the brain, it passes through two distinct populations of neurons. Scientists know the two cell types look and behave differently, and that the presence of both has been conserved across mammalian species, from mice to humans. What remains less clear is why the olfactory system needs two separate channels and what roles each plays in representing smells.

Tucker hopes that faster measurements, combined with newer ways of observing neural activity, can reveal differences that previous experiments could not capture.

For Tucker, the project reflects the kind of scientist he hopes to become. The fellowship supports both the biological research and the continued development of the microscope itself, combining engineering with basic neuroscience.

That combination has interested Tucker since before he arrived at NYU. Originally from Gainesville, Florida, he studied Biomedical Engineering at Boston University as an undergraduate and came to Shoham’s lab at NYU already knowing that he wanted to develop instrumentation for neuroscience.

“I had a pretty clear goal for my Ph.D., I knew I wanted to work on microscopes for neuroscience,” he said.

Winning the F31 required persistence. Tucker said preparing the application took months and ultimately produced roughly 40 pages of material spanning the proposed science, his training plan and his development as a researcher. His first application did not advance, and he later revised and resubmitted it. The process stretched across nearly two years.

He credits support from the NYU Tandon Ph.D. Writing Studio with helping prepare him for the demanding process. Earlier grant-writing training taught him how to explain specialized work within strict page limits and, more importantly, how to connect a proposed research project with a broader story about his development as a scientist.

That connection is particularly important for an NIH F31, Tucker said. Unlike a research grant focused only on a project, the fellowship also evaluates how the research will help train the applicant for an independent scientific career.

For Tucker, that makes receiving the fellowship especially meaningful.

“My dream is to one day lead a lab in this field,” Tucker said. “It feels good to be recognized that I really might have that potential.”