Chemical biology program offers students a unique career path
A National Institutes of Health (NIH) training program that trains graduate students in both chemistry and molecular biology aims to give these scholars new options for both scientific study and future career paths.
Jose Ricardo Moreno, a Ph.D. candidate in chemistry who researches the cellular underpinnings of cancer and other serious diseases, never studied biology as an undergraduate. He is now seeing how chemistry can drive innovative biological research leading to better understanding of disease and new treatments.
“As a synthetic chemist, my drive is ‘how can I synthesize or make new molecules,’” Moreno said. “It wasn’t until biology came into play that I began to see it had a big role to play in finding cures for diseases and finding ways that we can make chemistry a tool to improve the quality of life for human beings. The connection immediately becomes apparent.”
Moreno is one of six Ph.D. trainees supported by a Chemistry-Biology Interface Research Training Program grant, one of a class of NIH awards known as a T32 grant.
Awarded in 2016 by the National Institute of General Medical Sciences, the two-year program is intended to help students in each discipline better communicate and collaborate with their counterparts in the other discipline. This, in turn, can help them find research approaches they will need for burgeoning interdisciplinary careers in the pharmaceutical and biotechnology industries.
In a nutshell, the T32 program is all about finding more and better tools to solve biological problems, said program director Susan Forsburg, Gabilan Distinguished Professor in Science and Engineering and professor of biological sciences.
A unique identity impacting human health
What makes the chemical biology sandbox so interesting? The field harnesses chemistry’s quantitative methods of synthesis, analysis, and mechanism to make fundamental discoveries that impact human health. For example, as biologists identify new drug targets by studying the genome and cellular proteins, there is a need for chemists grounded in fundamental biology who can design, synthesize, manipulate and characterize molecules. And chemistry gives molecular biologists a deeper understanding of the chemical principles that underlie molecular interactions such as recognition, design, synthesis and reactivity.
“The idea here is that we are trying to give our students a unique identity as chemical biologists,” Forsburg said. “Trainees identify someone on the opposite program with whom they can have a co-mentor relationship and spend some time in that lab and learn something from the other side.”
Besides venturing into six-week mini-sabbaticals, they take several courses in the cross discipline.
Trainees are schooled in the responsible conduct of research fundamentals. They meet in a weekly journal club to hash over assigned research journal articles and hear prominent lecturers provide overviews of their research. The cadre pores over each paper and asks, ‘Why is this important and what makes it a good paper? What makes a good research problem? For that matter, what makes a good research program?’
The sciences converge
The T32 program’s focus on cross-training dovetails with the intensely collaborative direction in which science is evolving at USC, as exemplified at the Bridge Institute at the USC Michelson Center for Convergent Bioscience. This fall, chemical biologists will be among the prominent researchers from diverse areas across science and engineering who will move into their new home at the USC Michelson Center.
“Training grants add an extra dimension to graduate education that prospective students seek,” said Stephen Bradforth, USC Dornsife divisional dean for natural sciences and mathematics. “The training program offers professionalization components and opportunities to work in laboratories with multiple investigators that students simply wouldn’t find elsewhere. The fact that USC has received the award underscores the prominence of our chemical biology graduate program as well as the excellence of its research faculty.”
USC is one of about 30 U.S. universities awarded training grants in the T32 chemical biology program. While USC has several federally funded training grants, this is the first to reside solely within USC Dornsife. It provides stipends to help cover living expenses, tuition and medical insurance for three graduate students, which USC Dornsife matches to support three more.
Graduate student Jose Ricardo Moreno received a T32 training grant.
Mentored by Matthew Pratt, associate professor of chemistry and training grant deputy director, Moreno studies glycosylation — the modification of proteins by carbohydrates, how this process helps cancer cells thrive and how it might be disrupted to fight disease.
Now entering his second year as a T32 trainee, he will spend six weeks in the lab of Fabien Pinaud, assistant professor of molecular biology and director of The Single Molecule Biophotonics Group.
“I expect to be taking compounds made in the [Pratt] lab and learning to stain cells and use these compounds to see into the cell,” Moreno said. He will go very small-scale, using light-based microscopy techniques to detect, study and understand the properties of biomolecules at the cellular, subcellular and molecular levels.
Pathways to understanding
Dieu An Nguyen researches small RNAs (ribonucleic acids) and how cells regulate their production and activity in the lab of Carolyn Phillips, assistant professor of molecular biology.
Working with a tiny worm called C. elegans, Nguyen recognizes that the biological lens used to study an intact organism only reveals part of the mystery she is trying to unravel. Chemistry provides a different way of looking at a problem, she said.
“I’m just very excited — a lot of me likes going very in depth in science,” she said. “But part of me thinks I’m missing out on the larger picture of science. This [program] makes me feel I’m a more comprehensive scientist.”
On the chemistry side, she will be mentored by Lin Chen, professor of biological sciences and chemistry, working in the test tube to purify worm proteins and study their biochemical properties.
Looking through the lens of chemistry will enable her to see protein structure and biochemical properties of those proteins with more of an expert eye.
“You can account for much more detail or chemical properties in your biological model than you thought could have done before,” she said. “So the program just sort of opens up this horizon of possible collaborations in the future.”
Pathways to careers
Pratt sees the blossoming chemical biology field offering attractive career paths for Ph.D. graduates. “What they learn allows trainees to come out as full-fledged chemical biologists rather than just a chemist or a biologist,” he said.
Pratt cited the pharmaceutical industry as an eager employer of graduates with a knowledge base that spans both fields.
“A lot of companies are moving in the direction of biological therapeutics,” he said. “For example, there is big growth in therapeutic antibodies, where job candidates need to have good understanding of chemistry and biochemistry as well as the more biological areas such as exploring protein expression and purification.”
Caiqun Yu primarily works in the lab group of Chao Zhang, assistant professor of chemistry, to develop small molecules that inhibit protein kinases. Kinases are key controllers of biochemical pathways and perform an essential role in regulating cell growth, development and survival. Kinase dysregulation can lead to or worsen aggressive diseases such as cancer. One particular kinase mutation under study has been found to drive advanced melanoma.
Her cross-training experience under Chen will enable her to study X-ray protein crystallography, a form of high-resolution microscopy. Investigators believe this tool will shine a brighter light on the interactions between small-molecule inhibitors and kinases at the atomic level and ultimately aid in the design of new inhibitor drugs.
Yu hopes to work in the pharmaceutical industry and believes the pairing of chemistry and biology offers a natural fit and synergy. “I need this expertise and to learn new techniques,” Yu said. “The [T32] program helps provide an important bridge we need to connect those two programs.”
Now embarking on year two, the training group is developing its own esprit de corps while it prepares to welcome new members.
“I love the people there,” Yu said. “We share ideas. We’re also planning on doing a student organized journal club over the summer. I think it’s a good opportunity to continuously talk about science and read papers.”
The NIH is providing four slots for 2017–18, when the cohort may grow to include 13 first- and second-year trainees. The first annual meeting later this year will bring everyone together to celebrate the new collaboration as well as share results and insights.