Editor's note: Since this feature was written, the scientific research of Staples High School senior John Solder has been accorded more accolodates. At the Connecticut Science Fair over the last week, his project, "Optogenetic Interrogation of Prefrontal Cortex Dopamine D1 Receptor-Containing Neurons as a Technique to Restore Timing: A Novel Approach to Treat Prefrontal Disorders," won first-place honors in two categories: the Pfizer Life Sciences and Alexion Biotechnology. The awards were announced at the conclusion of the statewide fair on Saturday.
With a model skull in one hand and a laser pointer in the other, John Solder demonstrated a potential treatment for prefrontal brain disorders such as Parkinson's disease and Alzheimer's disease.
After he pressed a button on the laser pointer, light coursed through a connected fiber-optic cable into the prefrontal cortex region in the "brain" of the mock cranium. The demonstration is simple, but it encapsulates Solder's research in a nascent field of prefrontal brain disorder treatment called optogenetics.
"When you look at it, it doesn't seem that terribly complicated," Solder said. "But then there's tons of genetics and neuro-anatomy you have to take into account."
Within a year of entering this area of neuroscience, Solder, a Staples High School senior, has emerged as one of its most promising young researchers. He has garnered several prestigious awards for his optogenetics work and has been praised by neuroscientists at Yale University for an inventive and assiduous approach to his research. Alongside some of the nation's top optogenetics researchers, Solder is investigating treatments that could eventually restore significant amounts of cognitive function and offer more daily independence to individuals with prefrontal disorders.
Optogenetics has garnered attention in the scientific community not just for its promise, but also for its departure from the two principal approaches currently used to treat patients patients with prefrontal disorders.
With deep-brain stimulation, electrical shocks are delivered to a specific area in the prefrontal cortex, the part of the brain's frontal lobes that lies right behind the forehead. That method, however, cannot target a specific molecular signal pathway affected by a prefrontal disease.
The other main treatment option for prefrontal disorders is pharmacological. While drugs can target a specific molecular signal pathway, they flood the entire body, resulting in a treatment that is not region-specific. These molecular signal pathways are spread throughout the brain, so if the entire brain is flooded with a medication, then all of its molecular signal pathways are stimulated, rather than just the ones responsible for the disorder being treated. Stimulating other pathways outside the prefrontal cortex can produce undesirable side effects.
In comparison, optogenetics effectively harnesses the respective advantages of deep-brain stimulation and pharmacological treatment. Light can be directed to a specific part of the brain-- just as electricity would be administered to a target area through deep-brain stimulation. In addition, because the light-sensitive proteins are selectively expressed in the prefrontal cortex, light stimulation can affect specific molecular signal pathways.
The first step of the process involves isolating genetic codes for light-sensitive proteins in algae. Those codes are then inserted into neurons in the brain through viral exposure, which produces light-sensitive neurons. Only Cre+ neurons -- neurons that contain the Cre protein -- will express the genetic code for the light-sensitive proteins. Consequently, those neurons will react when exposed to light during optogenetics treatment.
In the Yale lab
Solder discovered the light-based treatment of optogenetics while reading an issue of the scientific journal, Nature, in 10th grade.
Before Solder embarked on optogenetics research, he sought to gain a grounding in prefrontal cortex research. As a result, he spent the summer after his sophomore year working in the laboratory of Amy Arnsten, a professor of neurobiology at Yale University.
"I had been interested in optogenetics before, and I was also interested in neurobiology," Solder said. "Then, I pursued neurobiology with Dr. Arnsten, but I still wanted to investigate optogenetics, and I combined the two into a neurobiological-optogenetics lab experience."
Solder quickly grasped the pivotal role the prefrontal cortex plays in facilitating the understanding of neuro-psychiatric disorders, Arnsten said.
"We normally don't have high school students, so that distinguished him to begin with," she said. "We'd have meetings that would be scheduled for an hour and we'd end up talking for several hours. He's a really brilliant young man who's interested in big ideas."
After his stint in Arnsten's lab, Solder last year moved to the lab of Ralph DiLeone, an associate professor of psychiatry and neurobiology at Yale. There, under the supervision of DiLeone, he began his optogenetics research working with post-doctoral fellow Ben Land and Kumar Narayanan, chief resident of neurology at Yale-New Haven Hospital.
"It was great to have him as a troubleshooter in a lot of ways, as well as an experimenter because he was looking at things in ways we hadn't looked at," Land said. "He asked a lot of really good questions. As a researcher, I thought he was really good."
Solder's work principally focused on testing optogenetics treatment on several mice. After the rodents were virally exposed to the light-sensitive proteins, fiber-optic cables were inserted into their brains, allowing for light to be shined into their prefrontal cortexes.
The trials with the mice centered upon them poking their noses into feeding chambers to receive food at 20-second intervals. After receiving the optogenetics treatment, the rodents burrowed for food closer to the 20-second markers, because the light stimulation enabled them to more accurately time their behavior.
While optogenetics has not yet been tested on humans, Solder thinks it will eventually be adopted as a treatment for individuals with prefrontal disorders.
"I think it holds great promise for treating prefrontal cortex disorders in the future, pending further human application research," he said.
If successful, optogenetics could restore enough cognitive function in a Parkinson's disease patient to allow him or her to take on more complex, timing-based activities like driving.
Solder, 18, continues to work in DiLeone's lab at Yale. Having accumulated about a year of experience in optogenetics research, he has already garnered several prestigious accolades for his work. Last year, Solder was a winner in the national Siemens Competition in Math, Science & Technology, which recognized the contributions of his optogenetics research to the greater scientific community. His optogenetics work at Yale also earned him a 2012 Neuroscience Research Prize from the American Academy of Neurology.
Not in a hurry
In June, Solder will graduate from Staples. He has not yet decided which college he will attend this fall. Regardless of his choice, Solder's mentors expect that he will continue to forge an inventive path.
"John is capable of listening to people's input and turning that input into his own ideas and then moving forward to make something really happen," said A.J. Scheetz, the chairman of the Westport school district's science department in grades six through 12. Scheetz has been an adviser to Solder for the last two years.
"I suspect that he's going to be one of those people who do two or three stunning things during the course of his time in college," Scheetz added.
Arnsten anticipates that Solder will eventually emerge as a catalyst for scientific innovation in his professional career.
"I can see him running a biotech [company] that cures all sorts of important things."
Solder, meanwhile, remains focused on more short-term goals. In addition to his optogenetics research, he captains the Staples robotics last team. The squad is currently preparing for this year's competitions, as it seeks to retain the robotics world championship it captured last year in St. Louis.
He said robotics and optogenitcs have similarities.
"They're both the exact same in terms of you have a problem you want to solve, and you've got to solve it," he said. "You have to create experiments and test procedures and prototypes. And hopefully you get your final robot or your scientific conclusion."
As for college, Solder said he intends to purse a diverse curriculum wherever he matriculates.
"I want to show up to college ready to investigate all kinds of sciences. I also want to get exposure to everything else," he added. "If optogenetics really is my one and only pride for science, then I will return. If I find something, I see no reason why I can't do something else. I have four years to figure it out."
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