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Ethan Buhr, a first year postdoctorial student, knows that “there is a line between trying to take on too much for a research project to be feasible” and “trying too little and having a project be boring.”

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Dr. Ethan Buhr extracts DNA from the eye to study the effects of the brain’s master circadian clock.

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Members of Buhr’s ophthalmology team study reports from experiments. They hope to find a way of resetting the brain’s master circadian clock.

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Buhr uses the UV light to spot different DNA.

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Buhr looks at the readout from a new computer that was purchased after Buhr won The Fight for Sight grant.

That comfortable medium was discovered this year through his eye research project on how changing seasons affect eyesight and general health — and Buhr was selected as a $20,000 Fight for Sight grantee.

Upon hearing the news, Buhr was grateful — and a bit reassured.

“It is a very good confirmation that our project seems reasonable,” Buhr wrote in an e-mail. “That a great organization like Fight For Sight is willing to contribute these funds to our work is very validating that we are on the right track.”

Buhr, alongside advisor Russell Van Gelder, plans to use the money to help pay for shared resources at the university and Fred Hutchinson Cancer Research Center. Specifically, the technologies used will allow Buhr to monitor the expression of all known genes simultaneously.

“We know that cells in the eye and in the circadian-clock region of the brain are measuring day length, and we know that the absence of the melanopsin protein affects this plasticity,” Buhr wrote. “Beyond that, any of many cellular pathways could be responsible or, at least, involved. By using microarray gene chips, we can scan the activity of all of these genes from a ‘summer’ mouse and a ‘winter’ mouse and arrange our data analysis to only detect differences between the two.”

Buhr studied circadian rhythms as an undergraduate and graduate student.

“I have always been very impressed with the precision of daily rhythm within our bodies and of all animals,” Buhr wrote.

His graduate studies emphasized the daily expression of genes in cells throughout the body and the way in which the cells synchronized themselves to the rest of the body.

Now, Buhr is taking a closer look at how vision is linked to seasons — notably, seasonal depression. And Seattle seems like a prime location to test this to Buhr.

“Seasonal depression and seasonal sleep changes are primarily the result of the modulating quantity and possibly spectral quality of light in temperate climates,” Buhr wrote. “This is especially evident in cities like Seattle where our summer days are very long and our winter days very short.”

Beyond just mere fascination, Buhr felt compelled to explore this process through research because he felt it was untouched territory within the ophthalmology field.

“I think that the synchronization of our bodies to our environment is a very under-appreciated biological process,” he wrote. “I suspect most people only really think about it when they have missed a night of sleep or travel across multiple time zones. … However, much research shows that chronically changing one’s circadian schedule can be detrimental to one’s health. The changing seasons is a natural way in which many species slowly adapt to changes in their environment and adapt their behavior accordingly.”

The execution of the research involves an elaborate process: A microarray of “gene chips,” sticky DNA fragments in known locations on a small glass slide, are used. All of the RNA is then removed from cells to allow it to stick to the corresponding sequence on a small glass slide. The non-binding RNA is rinsed off and, at that point, DNA fragments that have pieces of RNA stuck to them are made visible.

Buhr wrote: “If a gene was active in the cell, then the specific RNA would be produced, and at that position on the array, a double-stranded match would be measured. If a gene was inactive at that time, only the single-stranded DNA probe would be seen on the array. This can be done simultaneously for all known genes on a single microarray chip.”

The offered grant is for one year, which, he believes, is enough time to wrap up his project.

“After this time we will have collected and analyzed the data from the initial sets of experiments,” Buhr wrote. “This will surely give us many beneficial insights into the non-visual adaptation of the eye to changing light cycles.”

But “done” is hardly applicable in science if you ask Buhr.

“As with all of science, it is never ‘done,’” he wrote. “This will give us many more ideas and avenues to explore for the extended future.”

As a scientist who has utilized resources at the University of St. Thomas and Northwestern University, he can easily compare and contrast the quality of the UW’s program.

St. Thomas’ resources, Buhr recalls, were fairly limited as a result of the expansion of the biology department. And Northwestern’s resources were similar to that of the UW’s.

When it comes to faculty for Buhr, though, there is no comparison.

“I am not being boastful in saying that the research program in ophthalmology and visual sciences at University of Washington is one of the best in the world,” he wrote.

When Buhr gets as close to “done” as it gets, he plans to venture further into his studies, taking a broader look at the whole system to pin “responsible pathways.”

One eye on the microscope and another on the prize, $20,000 has marked the beginning of a new chapter in Buhr’s scientific quest.

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