Salk Institute for Biological Studies: InsideSalk

Salk Scholars Come to La Jolla for Summer Training

In the New York City borough of Brooklyn, summer was hot and muggy, as usual. Riding the crowded subway or bus to work during the week, commuters worried about the impending transit fee hike. On Sundays, some of them perused the outdoor flea market to shop for vintage wares and munch on pupusas or pizza by the slice.

These could have been the recollections of William ("Will") Mak and Diana Kachan, two Brooklyn residents who recently graduated from the City University of New York (CUNY) with plans to attend medical schools in the fall.

But they weren't.

Instead, Will and Diana came to work at the Salk Institute for the summer, after receiving the coveted Jonas E. Salk Scholarships. The scholarships were created in 1955 at the request of the late Dr. Jonas Salk, an alumnus of CUNY, when the city of New York wanted to celebrate his discovery of the Polio vaccine with a ticker-tape parade. He suggested that the money might have a better use.

The Salk Institute's participation with the scholarship program began in 2005. In addition to helping with medical school tuition, the students receive a salary and an allowance for living expenses while they perform research for eight weeks during the summer.

Diana and Will came to Salk from mid-June through the first week of August to work on projects that, for each of them, held personal importance.

A native of Belarus, the landlocked Easter European country where her parents still live, Diana, 28, moved to New York City in her early 20s through a work-exchange program and began taking courses at CUNY, where her interests turned first to chemistry, then physics, and ultimately biology.

"I just loved it," says Diana, who remembers considering a career in medicine many years earlier after volunteering at an orphanage for children who were handicapped from radiation exposure after the Chernobyl explosion. "[Biology] wasn't just about memorization and facts, but about real life. It wasn't until after I came to the U.S. that I realized this was something I want to do."

Diana is now enrolled in the M.D./Ph.D. program at the University of Miami School of Medicine. She plans to pursue both epidemiology and neurology. At Salk, she learned a theoretical approach to neurology, guided by Tatyana Sharpee, assistant professor in the Computational Neurobiology Laboratory.

Imagine that neurons are like rubber bands. If one end is anchored and the other stretched, then released, the "snap" that occurs is similar to the way a neuron receives input and fires its own signal down the chain. The snap looks like a spike when it is plotted on a graph, and so they are called spikes.

Scientists understand the physiology of neurons and how they create a spike, but what actually determines a spike, and what different patterns of spikes mean, is still unclear.

This is the focus of Sharpee's work. Using data collected by collaborators at the University of California, San Francisco from retinal cells and the relay cells in subcortical regions, she used a computer code to analyze how input spikes are transformed into sequences of output spikes.

Diana came to the lab with no experience in theoretical neuroscience, and only a little bit with computer programming. But after two weeks of reading computer programming textbooks at her desk, she managed to make some sense of things.

"See this portion of the code here?" she asked, scrolling down more than 500 lines on her computer screen. To the untrained eye, it looked like an e.e. cummings poem. "This is the section that I'm really interested in."

Sharpee had hoped for an acute response such as this.

"I think it is important to expose students to computational and theoretical techniques, even if these techniques are not going to the main focus of the their future research," she said. "Besides, Diana brought a fresh approach to our research.

"There's a practical side to this arrangement," Sharpee admits. "I had projects that I needed to get done. But also, in the field of neuroscience we are working toward the goal of merging theoretical and experimental techniques. We need a common language to do this, and by giving Diana theoretical exposure, this may help in the future."

Analyzing Gene Sequences

Working in Professor of Molecular Neurobiology Dennis O'Leary's laboratory alongside postdoctoral fellow Todd Kroll, Will's project focused on understanding whether a section of genetic code is responsible for development of the brain region that controls movement, including vision and balance, in mice.

"My research in New York was more behavioral than this," Will explained. "The project focused on measuring eye movement in patients to understand how stimuli could grab their attention. But my work in Dr. O'Leary's lab is much more 'wet' than what I'm used to."

He began at the computer, analyzing gene expression patterns that are published online, finding one that is complimentary to another gene that specifically identifies visual cortex. He then cloned the new gene into a plasmid vector so that it could be used to make a probe that will identify where this gene is turned on. Finally, he used the probe he generated to analyze thin brain sections with a staining technique that allowed him to see where the gene "appeared" in the overall developing brainscape.

"I wish that I could have done something like this for the summer when I was his age," admitted Kroll, who has worked in the O'Leary lab as a postdoctoral fellow for six years.

At the lab bench pouring careful measurements from bottles of buffer solution, or at the cryostat tissue preparation machine, Will, a preppy young man, appeared slightly slouched, as though about to give himself a hug. This is because he was born with scoliosis, an S-shaped curvature of his spine that restricts some of his movement and causes him daily pain.

"When I was in high school, I had my lower lumbar spine fused," he explained. "At the time, it dashed my hopes of joining the NBA or becoming a football player, but I dealt with it."

He can joke about it now, but it was his traumatic experiences working with doctors as a child and young adult that led him to study at the New York College of Osteopathic Medicine. One day he hopes to work as an orthopedic surgeon, focusing on pediatrics.

His experiences as a scoliosis patient are also what led him to choose this project in O'Leary's lab.

"Perhaps one day the discoveries in this lab will lead to cures for spinal deformities, or ways to prevent them from happening in the first place," he ventured. "It's really exciting for me to think that I could say, 'I helped with that research.' "

InsideSalk 10|08 Issue | © Salk Institute for Biological Studies