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Finding What Makes Fruit Flies -- And Humans -- Tick

J M Shenoy

Amita Sehgal knows how fruit flies regulate their bodies to the cycles of light and dark. Now if she could take that knowledge further perhaps, humans suffering from jet lag and insomnia may also profit.

Her research could help people reset their clocks, thrown out of joint by jet lag other factors. The discoveries could make soldiers more effective, and help psychiatrists treat their patients better. It might even save a few marriages.

Since such clocks exist in humans too, the insights from her experiments could offer some solace to those whose circadian rhythms -- as these patterns are termed by the scientific fraternity -- are out of sync with the world.

Sleepiness in workers, pilots and soldiers on the night shift, and maybe even some forms of depression, could be treated more effectively following the insights gained from experiments her team is doing, Sehgal says.

But all that is a bit premature; for now she is still dealing with fruit flies.

Sehgal, an associate professor of neuroscience and a Howard Hughes Medical Institute at the University of Pennsylvania, is senior author of an article published recently in Science that explains the molecular intricacies of a fruit fly's internal clock.

She zapped fruit flies with light pulses to analyze the biochemical consequences.

"The system [that breaks down proteins] is not unique to circadian rhythms," Sehgal says. "It's implicated in some cancer-causing pathways, and in cell cycles and cell division. The work has broad applications. We now have proteins or systems that you can target to reset your biological clock.

"Since so many human hormones rise and fall in circadian cycles, this effect on drug therapy seems to make perfect sense," Sehgal says.

The mechanisms that regulate the circadian rhythms of humans and other life forms, including bacteria, are similar to those regulating that of the fruit fly, she says.

"We are finding out every day that more and more in the human system might be controlled by our internal molecular clock; everything from our thresholds for pain, blood pressure and basal body temperatures to hormone cycles," she says. "If we understood exactly which component needs to be regulated to reset the biological clock, we could target just that component with drugs," she adds.

"Such drugs might aid treatment of jet lag and seasonal depression caused by absence of light in winter. It is hypothesized that other forms of depression involve clock genes. In addition, there's tentative evidence that these genes might influence whether people are naturally 'morning' people or 'evening' people."

There are data showing that drugs such as cancer drugs may work more effectively and with fewer side effects if they were given at a specific time of day. Since so many human hormones rise and fall in circadian cycles, this effect on drug therapy seems to make perfect sense, according to Sehgal.

Three years ago, the good doctor's team showed that proteins called "timeless" (TIM for short) and "period" (PER) decreased after a fly perceived light.

This year, Sehgal's team we figured out how TIM reduces in response to light. About 20 minutes after light stimulation, the fly body makes TIM break down, followed in a little time by PER. She wanted to find out what made these changes happen and found it in some cells in the fly's brain.

She began her study of the circadian rhythms of fruit flies partly because scientists already have an idea about their molecular basis, she says.

"The tools were there -- the genetic tools," she says, adding that what intrigued her was a chance "to find the molecular basis of behavior."

Sehgal is a native of New Delhi but lived with her parents in Australia and Germany and India since her father worked for the Indian government's tourism department.

Before starting her American educational career at Cornell University, Sehgal had studied in New Delhi, earning a master's degree in life sciences at JNU.

She had at one point seriously thought of going into law and had received admission for law as well as for life sciences. But she heard that getting admission to life sciences was tougher, and so she opted for the latter.

Then, during a visit to her sister in America in 1983, Sehgal began thinking seriously of joining an American school for graduate studies and a Ph D.

Sehgal is married to an American scientist and has two children Natanya and Anjali.

For an immigrant, the success of any endeavor has to do a lot about being assimilated, she says. One does not have to do research on fruit flies to know that by being pliable, picking up interest in mainstream activities such as baseball and interacting more with one's American colleague, one can connect wit others effectively.

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