We know it’s spelled Convergent Bioscience. But USC Dornsife sees the urgency in this heads-up rather than heads-down research mentality.
By Pamela J. Johnson • USC Dornsife
May 29, 2014 (Spring / Summer 2014 Print Issue)
The little jump was a heartbeat. Trivedi was looking at live, day-old zebrafish embryos. Using the zebrafish as a model, Trinh researches how the heart forms in the developing embryo. Considering that a leading birth defect in humans occurs during the development of the heart valve, Trinh’s research is crucial in identifying what can go wrong.
Still looking through the microscope, Trivedi nonchalantly mentioned that he could better analyze the data by creating an algorithm to “unwrap” the embryo.
Trinh’s heart jumped a little, too. Trivedi’s algorithm would reconstruct the developing embryo with red and green labels through a 3D computer simulation. This was a giant leap for Trinh, an expert biologist and geneticist, but admittedly no mathematician.
“Voilà,” said Trinh, a senior research scientist in the laboratory of Scott Fraser, Provost Professor of Biological Sciences and Biomedical Engineering at USC Dornsife. “We now have this.”
Trinh waved an arm toward her computer screen, depicting a developing zebrafish heart in 3D. The movie shows how the heart begins with two halves and slowly merges into one.
Those halves that meld to form one beating heart could be a metaphor for Fraser’s office layout.
Sitting across from Trinh is Trivedi, a Ph.D. student in bioengineering who developed the algorithm. Working next to Trinh is research scientist Thai Truong, a trained physicist. Among other pieces of equipment, Truong and his team built the two-photon light sheet microscope — to which they hold the patent — that created Trinh’s 3D movie. Although the zebrafish heart beats 150 times per minute, the microscope photographs so fast that the slides that became the movie were ultra-sharp.
By converging their fields, the molecular genetics of a beating heart — the scientists also use quail embryos as models — can now be visualized in real time.
“This could never be done simply by using pure genetics or pure physics or pure mathematics,” Trinh said. “It took the three fields coming together and sharing our expertise to create this.”
Fraser’s triple-threat system is a microcosm of the upcoming USC Michelson Center for Convergent Bioscience. In January 2014, retired orthopedic spinal surgeon Dr. Gary K. Michelson and his wife Alya donated $50 million to USC to fund the center bearing his name.
Bigger, Braver, Bolder
The center will be the hub of a new collaboration between USC Dornsife and the USC Viterbi School of Engineering that takes interdisciplinary research in biomedical sciences to new heights.
The USC Michelson Center will stand in the southwest quadrant of the University Park campus, home to most of the science and engineering buildings. The facility will house 20 to 30 principal investigators with laboratories employing hundreds of researchers and students.
The days of seeing a chemist clad in rubber gloves, toting a tray of liquid-filled flasks and beakers across campus to use a light or magnetic resonance imaging (MRI) microscope in an engineering building are nearing an end. Some of the most advanced microscopes in the world — like the GE DeltaVision OMX Blaze that can generate 3D images of objects at the nanometer scale — will be housed at the Michelson Center.
“This center will usher in a new age of exploration and innovation at USC,” said President C. L. Max Nikias. “It will unite the most gifted minds from many academic areas, creating a powerful partnership that will extend across several different disciplines.”
Along with the biologists, physicists, mathematicians and chemists at the center will be engineers, who will build the latest technology capable of taking precise measurements inside cells. Together they will tackle the biggest health challenges by first building a biological “knowledge base,” then expediting the detection and cure of diseases.
USC Dornsife Dean Steve Kay, professor of biological sciences, said systems biology — which integrates biological data to better understand how biological systems work — was a precursor to convergent biology.
“Systems biology was a great example of what you can begin to see when you bring mathematics, computational science and biological sciences together,” Kay said. “But convergence is something bigger. I think it’s bigger, braver and bolder.”
The Michelson Center will house Fraser’s laboratory and the lab of Kay, whose investigations have contributed to the understanding of the genetic basis for circadian rhythms, which serve as the body’s clock for timing the day/night cycle.
Kay noted how differently the engineer and biologist think.
“Engineers build things from the bottom up,” Kay said. “So they start off with a piece of paper and say, ‘Let’s design a new jet.’ The biologist takes a cancer cell and asks, ‘Why is this cancer cell responding to that drug but not this one? What is going on inside the cell that allows that to happen?’ So they start from the top down.
“Merging these together is a completely different process than, for example, the pharmacologist working with a biochemist or a cell biologist working with a developmental biologist,” Kay said. “Convergence is about bringing multiple people together with very different training and expertise.”
Kay emphasized that USC Dornsife’s partnership with USC Viterbi and its dean, Yannis C. Yortsos, will be critical to advancing not only collaboration, but real-world solutions.
“The hardcore, physics-based, material scientists might not realize the nanowires they were creating can become an essential biosensor and ultimately be used as a diagnostic for diseases,” Kay said. “But working in a convergent environment can bridge that gap.”
For a recent Proceedings of the National Academy of Sciences paper, Kay’s lab worked with chemical engineers at the University of California, Santa Barbara. Through analysis and computer modeling, the collaboration shed light on factors that affect circadian rhythms, the roughly 24-hour oscillations of biological processes that occur in many living organisms.
Circadian rhythms help people adapt to predictable daily changes in the environment. But too much light at night, not enough sleep, or eating or exercising too late can offset the necessary nighttime-phase cellular activity. This can lead to diabetes, heart disease and obesity. Alzheimer’s disease and some liver conditions also have been linked with so-called low-amplitude rhythms.
Kay’s effort aims to better predict how to target circadian proteins with therapeutics that can battle sleep disorders and neuropsychiatric diseases such as bipolar disorder.
Kay’s paper is an example of how biologists and chemical engineers can work together to fight key disorders, but merging such widely dispersed fields has culturally been difficult.
“First and foremost, there must be a willingness to bring them together,” Kay said. “Then, you need a venue.”
Enter the Michelson Center.
“This will be a place to meet and create an integrated culture,” Kay said, adding that the facility is expected to help draw even more talented researchers to push the frontiers of science at USC Dornsife.
Now I See
Fraser, director of science initiatives at the university with a joint appointment at USC Viterbi, is among the rare scientists who are experts in biology and physics. In Fraser’s lab, biologists love nothing more than to “steal tricks” from engineers.
There’s Ellis Meng, assistant professor at USC Viterbi, who has a spectacular ability to make devices.
“So she’s making electrodes that can float in the brain and let us record from many neurons at once,” Fraser said.
His team “steals” techniques from others such as Carl Kesselman, professor of industrial and systems engineering, who makes tools that let researchers interact with complex data sets.
“The important thing for me is that the way he structures these fosters my analysis and my collaboration with others,” Fraser said. “He’s truly an artist who makes the tools so they can aggregate heterogeneous data.”
A perfect example of convergent bioscience came during Arnold and Mabel Beckman Foundation meetings, Fraser recalled. The foundation invited nanoscientists and chemists working on artificial photosynthesis — or synthetic ways to harvest solar energy and turn it into chemical energy that could eventually charge a battery.
Also invited were bioengineers seeking to restore vision, such as University Professor Mark Humayun, professor of biomedical engineering, and cell and neurobiology at USC Viterbi.
During these gatherings, participants realized maybe they could take the chemicals they were using for artificial photosynthesis and inject them into the human eye to see whether the injection could make the cells that don’t normally, respond to light in the retina, Fraser said.
“And it looks like it’s working,” he added.
Humayun, after nearly 20 years of work, became the main researcher behind the world’s first commercially available artificial retina, a breakthrough that helps the blind see.
“The Beckman Foundation decided to hold meetings, intentionally trying to stir the pot,” Fraser added. “Now imagine if you had that whole thing working every day, stirring the same sort of pot.”
Underscoring the vision and support of Nikias and Provost Elizabeth Garrett, Executive Vice Provost Michael Quick said that convergent bioscience at USC is about more than a building or creating tools.
He cited Kay’s comparison of people who do heads-down research to those who do heads-up research.
“That is, are they looking down on the lab bench just focusing on their own science, or are they looking up and around and saying, ‘Who can I pull into a group to go solve this problem? It’s not so much what these people do, it’s how they do it that determines whether they’re part of this convergent bioscience movement.”
The education component of convergent bioscience is key, said Quick, professor of biological sciences at USC Dornsife. He pointed to the Health, Technology and Engineering program at the Keck School of Medicine of USC, which brings together medical and engineering Ph.D. students to work in clinics learning about problems that must be solved. Then they work in the laboratory creating medical devices.
“Ph.D. students should be well-trained in a discipline,” Quick said, “but they have to learn the mentality of interaction.”
Distinguished Professor of Chemistry Arieh Warshel recalled the difficulty in collaborating with researchers outside his field in the early stages of his scientific career in the 1960s and ’70s.
“If I went to the best professors in electricity to ask them about a problem I wanted to solve, for example models for electrostatic effects in proteins, they had no clue what I was asking,” said Warshel, who in October 2013 won the Nobel Prize in Chemistry for helping to develop the principles behind computer simulations now indispensable in the study of the action of proteins.