This was originally published in November 2022 Breakthroughs.
Synthetic biology is a robust interdisciplinary field that uses tools and concepts from engineering, physics and computer science to build new biological systems. At Feinberg, scientists are pursuing synthetic biology research to address the health challenges and diseases that humans face. It has been described as using biology’s mechanisms of creating molecules to make new molecules biology never knew about. While some may think it’s science fiction, new technology makes synthetic biology a reality.
While the field is relatively young, synthetic biology is thriving at Northwestern and driving innovation. Establishing synthetic biology as a research priority at Feinberg has bolstered the university’s ability to harness the research and translate it to real-world scenarios.
The Center for Synthetic Biology was established in 2016 to enable scientists from Feinberg, the McCormick School of Engineering and the Weinberg College of Arts and Sciences to engage in collaborative research involving the emerging field. When the Simpson Querrey Biomedical Research Center opened in 2019, the university dedicated space on the 11th floor to allow for collaboration on the Chicago campus.
“Synthetic biology is an exciting field showing enormous promise for scientific impact across many areas—from medicine to national security,” said Milan Mrksich, PhD, professor of Cell and Developmental Biology, vice president for research and founding director of the Center for Synthetic Biology. “Northwestern’s leadership in synthetic biology also helps fuel our translational impact, by bringing our innovations from the lab into the marketplace where our research can directly benefit people.”
Expanding funding and impact
As the center continues to grow and bring in new faculty to Feinberg, funding is expanding as well. Arthur Prindle, PhD, assistant professor of Biochemistry and Molecular Genetics, received the Early Career Award for Scientists and Engineers (ECASE-Army) from the U.S Army Research Office in 2021. This award allowed his lab to pursue research on bacterial communities known as biofilms. His lab studies endogenous neurotransmitter production by biofilms, or densely packed communities of bacteria, which could be engineered for strategic advances in in-field biosynthesis and sensing, including within the human gut microbiome.
In his research, Prindle thinks about synthetic biology as programming the cell.
“If we understand the cell as a machine, we can seek to rearrange the parts of the cell to do a new function,” Prindle said.
His research into biofilms continues as Prindle received a R35 Award funded in August 2022. The goal of this work is to uncover how emergent metabolic coordination and cell-to-cell signaling give rise to these collective behaviors in biofilms. This is important because it will reveal new ways to target the unique properties that make biofilms resilient and could impact human health through addressing antibiotic resistance and finding new ways to treat infection.
“With bacterial infections, we want to study biofilms to understand what allows them to thrive and then target that,” Prindle said. “Mechanisms inside biofilms keep the bacteria growing slowly, which allows it to dodge antibiotics which target rapidly growing bacteria. We could also use synthetic biology to engineer such bacterial communities to monitor and treat disease within the human gut microbiome.”
Often scientists encounter scientific problems for which the technology has yet to be developed to address them. When this happens, investigators can develop the technology they need to address the problem.
Yogesh Goyal, PhD, assistant professor of Cell and Developmental Biology, is doing just that. He joined Feinberg in February 2022 and his lab is studying cancer drug resistance and what is different about cells that develop and become resistant to cancer drugs. He developed a tool called FateMap, which is a framework that combines DNA barcoding with single-cell RNA sequencing to reveal the fates of hundreds of thousands of cells exposed to anti-cancer therapies. His lab is now expanding the applications of such synthetic biology techniques to disparate biological questions, from host-viral interactions to cancer to building synthetic embryos.
Goyal is growing into the role and building his lab. “I’m very grateful for the mentorship I’ve received at Northwestern and opportunity to do this work,” Goyal said. “I’ve been building my lab in a way that our questions — inspired by synthetic biology — have no disciplinary boundaries, and we’re intentional in the building the team to include members with math, biology and engineering backgrounds so we can approach questions from unique perspectives.”
Identifying Protein Structures
High-throughput approaches are designed to increase efficiency and translation to the real world. Recent research published in Proceedings of the National Academy of Sciences (PNAS) identified a challenging protein design puzzle using a unique high-throughput approach.
Gabriel Rocklin, PhD, assistant professor of Pharmacology and senior author of the study, noted that the approach could enhance the development of new therapeutics and biotechnology tools.
Protein folding is an essential cellular process that enables proteins to function properly and avoid contributing to disease. As the scientists tried to apply synthetic biology to this problem, one major challenge they ran into when trying to computationally design new protein structures in the laboratory is that most designed proteins are unable to fold into their designed structures when tested.
In the PNAS study, the investigators designed over 10,000 new ɑββɑ proteins and by using specialized high-throughput experiments, they discovered that more than one-third of them folded into stable structures. The investigators were also able to identify the biophysical properties that stabilize ɑββɑ proteins as well as compare different protein design methods, according to Rocklin.
“By making changes to our design protocol, we increased our design success rate from two percent to above 30 percent. This clarified better ways to design ɑββɑ proteins and also helped us understand what makes them stable or unstable,” Rocklin said.
The current approach is applicable for any computational protein design effort. Additionally, ɑββɑ proteins also have the potential to be developed into therapeutics by modifying their surfaces so they can bind to therapeutic targets, according to Rocklin.
“These proteins can become even more stable by connecting the two ends of the ‘M’ together to form a loop, which could be an exciting strategy for designing therapeutics,” Rocklin added.
The possibilities are endless with synthetic biology, and research on both the Chicago and Evanston campuses, has led to start-up companies established by Northwestern faculty members to provide new technology. In 2021, five of the 19 faculty startups came from synthetic biology.
Mrksich, Prindle, Goyal and Rocklin are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Melissa Rohman contributed to this article.
