SMU chemist Alex Lippert receives 2017 NSF CAREER Award

 

Alex LippertSMU chemist Alex Lippert has received a National Science Foundation CAREER Award, expected to total $611,000 over five years, to fund his research into alternative internal imaging techniques.

NSF CAREER Awards are given to tenure-track faculty members who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research in American colleges and universities.

Lippert, an assistant professor in the Department of Chemistry in SMU’s Dedman College of Humanities and Science, is an organic chemist and adviser to four doctoral students and five undergraduates who assist in his research. Lippert’s team develops synthetic organic compounds that glow in reaction to certain conditions. For example, when injected into a mouse’s tumor, the compounds luminesce in response to the cancer’s pH and oxygen levels. Place that mouse in a sealed dark box with a sensitive CCD camera that can detect low levels of light, and images can be captured of the light emanating from the mouse’s tumor.

“We are developing chemiluminescent imaging agents, which basically amounts to a specialized type of glow-stick chemistry,” Lippert says. “We can use this method to image the insides of animals, kind of like an MRI, but much cheaper and easier to do.”

Lippert says the nearest-term application of the technique might be in high-volume pre-clinical animal imaging, but eventually the technique could be applied to provide low-cost internal imaging in the developing world, or less costly imaging in the developed world.

But first, there are still a few ways the technique can be improved, and that’s where Lippert says the grant will come in handy.

“In preliminary studies, we needed to directly inject the compound into the tumor to see the chemistry in the tumor,” Lippert says. “One thing that’s funded by this grant is intravenous injection capability, where you inject a test subject and let the agent distribute through the body, then activate it in the tumor to see it light up.”

Another challenge the team will use the grant to explore is making a compound that varies by color instead of glow intensity when reacting to cancer cells. This will make it easier to read images, which can sometimes be buried under several layers of tissue, making the intensity of the glow difficult to interpret.

“We’re applying the method to tumors now, but you could use similar designs for other types of tissues,” Lippert says. “The current compound reacts to oxygen levels and pH, which are important in cancer biology, but also present in other types of biology, so it can be more wide-ranging than just looking at cancer.”

“This grant is really critical to our ability to continue the research going forward,” Lippert adds. “This will support the reagents and supplies, student stipends, and strengthen our collaboration with UT Southwestern Medical Center. Having that funding secure for five years is really nice because we can now focus our attention on the actual science instead of writing grants. It’s a huge step forward in our research progress.”

Lippert joined SMU in 2012. He was a postdoctoral researcher at University of California, Berkeley, from 2009-12, earned his Ph.D. at the University of Pennsylvania in 2008 and earned a bachelor’s in science at the California Institute of Technology in 2003.

The National Science Foundation (NSF) is an independent federal agency created by Congress in 1950 “to promote the progress of science; to advance the national health, prosperity, and welfare; to secure the national defense…” NSF is the funding source for approximately 24 percent of all federally supported basic research conducted by America’s colleges and universities.

— Kenny Ryan

 

Research: Blue-light blues – SMU study shows how artificial lighting can interfere with health, sleep, even animal migration

A NASA image of Earth’s city lights using data from the Defense Meteorological Satellite Program.
An image of Earth’s city lights using data from the Defense Meteorological Satellite Program. (Credit: NASA)

An SMU study funded by the National Institutes of Health is unraveling the mystery of how blue light from residential and commercial lighting, electronic devices and outdoor lights can interfere with the natural body clocks of humans, plants and animals – and the negative consequences it can bring.

Exposure to blue light is on the increase, says SMU chemist Brian Zoltowski, who leads the study, “Protein : Protein interaction networks in the circadian clock.”

At the right time of day, blue light is a good thing. It talks to our 24-hour circadian clock, telling our bodies, for example, when to wake up, eat and carry out specific metabolic functions. In plants, blue light signals them to leaf out, grow, blossom and bloom. In animals, it aids migratory patterns, sleep and wake cycles, regulation of metabolism, as well as mood and the immune system.

But too much blue light — especially at the wrong time — throws biological signaling out of whack.

“As a society, we are using more technology, and there’s increasing evidence that artificial light has had a negative consequence on our health,” said Zoltowski, an assistant professor in the Department of Chemistry in SMU’s Dedman College of Humanities and Sciences.

“Our study uses physical techniques and chemical approaches to probe an inherently biological problem,” he said. “We want to understand the chemical basis for how organisms use light as an environmental cue to regulate growth and development.”

SMU Assistant Professor of Chemistry Brian Zoltowski
SMU Assistant Professor of Chemistry Brian Zoltowski

Zoltowski’s lab was awarded $320,500 from the National Institute of General Medical Sciences of the National Institutes of Health to continue its research on the impact of blue light. They are studying a small flowering plant native to Europe and Asia, Arabidopsis thaliana – a popular model organism in plant biology and genetics, Zoltowski says.

Although signaling pathways differ in organisms such as Arabidopsis when compared to animals, the flower still serves an important research purpose. How the signaling networks are interconnected is similar in both animals and Arabidopsis. That allows researchers to use simpler genetic models to provide insight into how similar networks are controlled in more complicated species like humans.

In humans, the protein melanopsin absorbs blue light and sends signals to photoreceptor cells in our eyes. In plants and animals, the protein cryptochrome performs similar signaling.

Much is known already about the way blue light and other light wavelengths, such as red and UV light, trigger biological functions through proteins that interact with our circadian clock. But the exact mechanism in that chemical signaling process remains a mystery.

“Light is energy, and that energy can be absorbed by melanopsin proteins that act as a switch that basically activates everything downstream,” Zoltowski said.

Melanopsin is a little-understood photoreceptor protein with the singular job of measuring time of day. When light enters the eye, melanopsin proteins within unique cells in the retina absorb the wavelength as a photon and convert it to energy. That activates cells found only in the eye — called intrinsically photosensitive retinal ganglian cells, of which there are only about 160 in our body. The cells signal the suprachiasmatic nucleus region of the brain.

“We keep a master clock in the suprachiasmatic nucleus — it controls our circadian rhythms,” he said. “But we also have other time pieces in our body; think of them as watches, and they keep getting reset by the blue light that strikes the master clock, generating chemical signals.”

The switch activates many biological functions, including metabolism, sleep, cancer development, drug addiction and mood disorders, to name a few.

“There’s a very small molecule that absorbs the light, acting like a spring, pushing out the protein and changing its shape, sending the signal. We want to understand the energy absorption by the small molecule and what that does biologically.”

The answer can lead to new ways to target diabetes, sleep disorders and cancer development, for example.

“If we understand how all these pathways work,” he said, “we can design newer, better, more efficacious drugs to help people.”

Written by Margaret Allen

> Read the full story at the SMU Research blog