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Hang Lu develops micro-tools that may help doctors correct diseases

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AAAS Fellow Hang Lu in her Georgia Institute of Technology laboratory with samples of the nematodes she studies. (Photo: Marsha Walton)

Since she was a teenager, Hang Lu has made navigating and connecting complex, disparate worlds look easy. Moving from China to Colorado as a teenager, her mastery of science and mathematics served her well even before she was fluent in English.

"I fit right into the science and math classes, because the symbols were the same. Even in chemistry class, I could guess the English words and get the chemical formula correct," she says.

Lu earned her Ph.D. in chemical engineering at Massachusetts Institute of Technology. "I was a physical scientist, trained as an engineer, and I decided that I wanted to do something a bit different," says Lu, \so I went to a medical school environment to do my postdoc."

She worked with neurogeneticist Cori Bargmann, who now heads President Barack Obama's BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies). "That was really fortuitous," recalls Lu. "I joked with her, 'I don't know which random synapse fired, but it was a fantastic experience!' "

Now an assistant professor of chemical and biomolecular engineering at Georgia Tech, Lu rigorously and creatively combines engineering and biology. Navigating both disciplines, she says, means realizing concepts that work in one application may go out the window in the other.

"You have to understand what the biological questions are and then you have to know what tools are available and match them appropriately. If they are not appropriate, you can design a lot of fancy devices that don't give you any information," she said.

She uses a common biological model—the tiny nematode, or roundworm, Caenorhabditis elegans (C. elegans)—as a first step in unlocking clues to the human brain.

The nematode's genome is related to the human genome, therefore, when Lu's team finds candidate genes or pathways that may affect processes in certain diseases in the worm, it can give clinicians some headway in finding answers for human subjects.

"The cool part is, we will be able to give hints to the geneticists on where to look. Instead of looking at tens of thousands of putative things, we can narrow that down for the human geneticist to look at," she said.

While her lab can do some experiments and analyses faster and more efficiently than traditional biology labs, she also is developing engineering methods and technologies to get information that can't be obtained with macro scale experiments.

Working with electrical and mechanical engineers, she is using microtools and nanotools, such as BioMEMS (Bio Micro-Electro-Mechanical Systems) to get information about disease mechanisms, and to observe how normal and abnormal cells behave. She uses microfluidic chips to look inside the nematodes using optical techniques.

"We integrated a lot of quantitative imaging techniques, as well as computer science techniques like artificial intelligence, as a way to mine the information out of these pictures," says Lu.

These tools allow Lu's team to do more than simply detecting mutations or behaviors in biological systems. They also have the capability of sending information to those systems, which could be used to correct diseases, using molecular tools such as sensors, actuators, and implantable devices.

Computers can do some things, like discern subtle differences and mutations in these tiny worms, much better than a human brain can.

She says her nematode analyses can be compared to a computer's "understanding" of someone's movie preferences. Just as Netflix may come up with a perfect movie suggestion, a computer can identify a worm characteristic that a human researcher may not have thought to examine.   

"It's essentially a data-mining process," says Lu.

While some of her engineering approaches involve sophisticated tools, like clean rooms and micro-fabrication, other successes need just simple equipment and ingenuity.

That was the case for some hardware designs in optogenetics, a method to turn neurons on and off with light.

"We wanted to shine light on different parts of a worm, to be able to control and alter its behavior, to figure out how the circuitry actually produced the behavior of the animal," explains Lu.

Her lab has accomplished that by hooking up a microscope with a projector (the same kind used to show a PowerPoint presentation in a classroom). Different colors of light can be directed to the head or tail of the animal to control the contraction of muscles. Their relatively simple setup, Lu says, allows them to interrogate the worm's nervous system, learn more about how circuits behave, how behaviors are produced, and how genes, the environment and drugs can produce or modulate behavior.

Lu says that in the long-term she's interested in getting better understanding of psychiatric and developmental neural conditions, such as autism and schizophrenia.

"We're trying to figure out what genetic or genomic changes might be happening in the brains of this sort of system. And we're going to use some of these model systems to answer those questions because they are more amenable to genetic and genomic manipulation."

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AAAS Fellow Hang Lu in her Georgia Institute of Technology laboratory with samples of the nematodes she studies. (Photo: Marsha Walton)
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Marsha Walton