UCSD - University of California - San Diego

04/27/2026 | Press release | Distributed by Public on 04/27/2026 10:16

The Engineer Who Taught Cells to Behave

Published Date

April 27, 2026

Article Content

On paper, Bernhard Palsson builds computer models. In practice, he builds a playbook to make living systems predictable enough to design and harness them for specific uses.

His work bridges the industrial and the medical - from using microbes as chemical factories to predicting how pathogens will respond to antibiotics. Most people encounter the ripple effects of his work without realizing it, through everyday materials whose "building-block" chemicals can now be brewed by engineered microbes, including ingredients used in spandex fibers.

Author of more than 800 peer-reviewed papers, holder of 46 patents and founder of eight companies, Palsson values simple curiosity, but also translating insight into action.

"I am attracted to doing something useful," said Palsson, who is the Y.C. Fung Endowed Professor of Bioengineering at the Shu Chien-Gene Lay Department of Bioengineering (Jacobs School of Engineering), Qualcomm Institute affiliate and professor of pediatrics at University of California San Diego.

"That's a big driver - making something happen."

Volcanoes and a ticket to impact

Palsson's journey began in Iceland, where he was born and raised in an entrepreneurial family. His father and grandfather set an example by launching a grocery store; his father also built a lithography and printing business.

"In Iceland, there's a lot of energy, hydro and thermal, used for chemical processing," says Bernhard Palsson. "That motivated me." (Photo by Tomas Malik)

Palsson's natural curiosity and drive were piqued by the power of his natural surroundings.

"In Iceland, there's a lot of energy, hydro and thermal, used for chemical processing," he said. "That motivated me."

Chemical engineering seemed like a natural fit. For his studies, Palsson first enrolled at the University of Iceland Reykjavík, before moving to the United States because he believed the country offered "the best education in the field."

In 1984, Palsson graduated with a Ph.D. in chemical engineering from the University of Wisconsin-Madison and was offered a faculty position at the University of Michigan.

Following interesting problems

At the University of Michigan, he found himself immediately pushing the traditional boundaries of chemical engineering. For Palsson, the interesting questions in the 1980s and 90s were biological ones.

"We had new fields developing called metabolic engineering, tissue engineering and so forth," he recalled. "It was obvious to me that was where the growth was."

Growing and controling bone marrow stem cells (like shown here) outside the body is the focus of some of Bernhard Palsson's early work. (Image by Chinmaya Mahapatra via Wikimedia Commons CC3.0)

Palsson threw himself into one of regenerative medicine's hardest practical problems: how to grow and control bone marrow stem and progenitor cells outside the body. If these cells could be reliably grown and controlled outside the body, lifesaving therapies would become more available, more predictable and easier to manufacture at scale.

The challenge wasn't simply getting cells to survive; it was coaxing the right cells to expand while preserving the delicate balance between self-renewal and differentiation in a system with limited nutrients and oxygen.

Approaching bone marrow less like a petri dish specimen and more like a living production system subject to quantitative analysis and experimental manipulation, Palsson and his team built an early bone-marrow "factory line." This culture system was continuously refreshed with nutrients flowing in, wastes flowing out, and key variables (such as oxygen levels and when to harvest the cells) fine-tuned to keep the clinically relevant cell populations expanding.

In 1988 he co-founded his first company, Aastrom Biosciences (now Vericel Corporation), in an early effort to turn this new stem-cell science into a scalable production process that could reach patients.

"For the longest time, founding companies was not considered clean, not academically pure," Palsson recalls. "Of course, today the view is different. But unlike other academics, I was always very comfortable with operating off campus."

When UC San Diego was looking to recruit faculty members with strengths in tissue engineering, Palsson was an obvious choice.

Reverse-engineering cell metabolism from genes

Arriving at UC San Diego in 1995, with appointments in both engineering and pediatrics, Palsson continued to explore how to measure - and ultimately control - cell behavior outside the body. He also kept his eyes open for interesting new problems.

As whole-genome sequencing (a method for reading an organism's complete set of genetic instructions) took off in the late 1990s, Palsson found a new question worthy of his attention: Could a cell's entire metabolism be represented by a computer model grounded in genetic information, so scientists could predict what the organism could and couldn't do before running a single lab experiment?

Palsson and Jeremy S. Edwards use the bacterial genome of E. coli (shown here) to develop an in silico (computational) model of E. coli metabolism that is adopted by scientists worldwide for research and industrial purposes. (Image courtesy of Pixabay)

The answer came first in the form of a 1999 Journal of Biological Chemistry paper published by Palsson and Jeremy S. Edwards, then a graduate student in Palsson's lab who is now Distinguished Professor of Chemistry and Chemical Biology at the University of New Mexico. The work used one of the first fully sequenced bacterial genomes (of H. influenzae Rd) as a blueprint to reconstruct the organism's metabolism as a single, computable network. More specifically, the researchers assembled a large reaction map (488 reactions acting on 343 metabolites) and then used a stoichiometric "bookkeeping" approach to map the cell's capabilities.

They soon extended this strategy to flagship organisms like E. coli. In a 2000 Proceedings of the National Academy of Sciences paper, Palsson and Edwards completed an in silico (computational) model of E. coli metabolism. This model was adopted by scientists worldwide to design and interpret laboratory experiments, as well as to engineer bacterial strains for industrial purposes.

An expanding circle of questions

As often happens in science, answering one question led to a host of others, and Palsson was not shy about asking them.

Could they model gene regulation of a whole organism, not just its metabolism?

The answer was "yes." Markus Covert, a doctoral student in Palsson's lab who is now Shriram Chair of the Department of Bioengineering at Stanford University, led work published in a 2004 Nature paper demonstrating the first genome-scale computational model of the gene regulatory system in E.coli. The model identified 115 previously unknown regulatory mechanisms, as well as new regulatory interactions for previously undescribed genes.

"We have demonstrated that we can reverse-engineer a cellular regulatory system at the genome scale," said Palsson in a UC San Diego Jacobs School of Engineering press release, "and then use that model to systematically gain new knowledge about how the cell functions."

Could they extend genome-scale modeling to human metabolism?

Again, "yes." In 2007, Palsson's team (including Natalie C. Duarte, Scott A. Becker, Neema Jamshidi, Ines Thiele, Monica L. Mo, Thuy D. Vo and Rohith Srivas) painstakingly assembled a first-of-its-kind metabolic network published in Proceedings of the National Academy of Sciences that contained more than 3,300 known human biochemical transformations. The model provided a new way to hunt for better treatments for hundreds of human metabolic disorders, from diabetes to high cholesterol.

The work was later extended in a highly cited 2013 Nature Biotechnology paper describing Recon 2, a community-driven, consensus reconstruction of human metabolism.

The questions - and answers - from the Palsson lab just kept coming.

As the models matured, Palsson pushed them out of the lab into startup companies. Genomatica was an early bet that "in silico" biology could change manufacturing by guiding the design of microbe-made chemicals; later, GT Life Sciences (2008) and Sinopia Biosciences (2014, incubated in the UC San Diego Qualcomm Institute Innovation Space) carried that predictive, data-driven approach deeper into industry and medicine.

Design. Build. Test. Learn.

In the meantime, a group was looking for someone to lead a new kind of research center at the Technical University of Denmark (DTU).

Funded by the Novo Nordisk Foundation, the new center of excellence would bridge the traditional academic-industry divide and strengthen Denmark's position in advanced bioprocessing and bioengineering. To lead the initiative, its CEO had to possess an unusual blend of academic research excellence and entrepreneurial experience.

In December 2010, a ceremony was held to mark the opening of Novo Nordisk Foundation Center for Biosustainability - with Palsson as its founding leader.

As the center was being created from the ground up, its research team initially focused on bringing a new level of understanding and control to microbial cell factories, which use microorganisms, such as bacteria, yeast or fungi, engineered to act as biological production facilities.

"Microbial cells are used to make many products - lager beer, insulin and industrial enzymes," said Palsson. "This was very much trial and error, a kind of 'black box' space. There was a much better way of engineering them and teaching them to do what you wanted them to do."

An international consortium of researchers assembles Recon 2, which is liked to Google Maps for its ability to merge complex details into a single, interactive picture. For example, researchers looking at metabolism's impact on tumor growth can zoom in on the "map" for finely detailed images of individual metabolic reactions or zoom out to look at patterns and relationships among pathways or different sectors of metabolism. (Image by Anna Dröfn Daníelsdóttir, Freyr Jóhannsson, Soffía Jónsdóttir, Sindri Jarlsson, Jón Pétur Gunnarsson & Ronan M. T. Fleming from the University of Iceland)
Palsson and colleagues sequence the genome of Chinese hamster ovary cells, which produce therapeutic proteins to treat cancer, diabetes and autoimmune diseases. (Image from Togo picture gallery maintained by Database Center for Life Science via Wikimedia Commons CC 3.0)

The improved approach Palsson had in mind used basic genetics to build models, then predictions from these models to manipulate the genome to create better microbial "production hosts." Palsson and his colleagues elevated this process into an integrated loop: design, build, test, learn. Then repeat. The approach quickly bore fruit.

One of the group's signature accomplishments involved Chinese hamster ovary (CHO) cells, the tiny workhorses that produce many therapeutic proteins, including treatments for cancer, diabetes and autoimmune diseases. Palsson and colleagues sequenced the genome of CHO in 2011, providing the field with a reference map so scientists could better find their way.

Beyond CHO, the center became an engine for sustainable biotechnology: teams used "design-build-test-learn" cycles to turn cells into reliable producers of useful molecules, then pushed the best ideas past the usual academic stopping point. The impact wasn't just papers; it showed up in real products and industrial practice, from fermentation-made ingredients and specialty chemicals to biomanufactured melatonin and new biological approaches for agriculture.

By the time Palsson stepped down as CEO of the Novo Nordisk Foundation Center for Biosustainability in 2022, the center had published upward of 1,800 research papers; spun out over 35 companies; and launched hundreds of distinguished careers in the field.

The Palsson lab identifies the conditions for cell metabolism to emerge on early Earth, shedding new light on the origins of life itself, along with the fundamental nature of biological carbon fixation. The discovery shows promise for improving carbon-capture technologies.

Continuing to 'make something happen'

Back at UC San Diego, where Palsson had retained his appointments and added an affiliation with the university's Qualcomm Institute, Palsson's Systems Biology Research Group kept churning out high-level research.

The group shed light on a wide range of topics - the team provided insight on the possible origins of life (which also had implications for designing novel carbon capture methods to combat climate change), and developed a method to use bacteria as living test tubes to study human gene mutations and rapidly screen chemicals for their potential drug use.

Among the problems that has held Palsson's attention is the growing resistance of disease-causing agents to currently available drugs.

"Antimicrobial resistance is going to be a main challenge of 21st century medicine," Palsson said. "Tens of millions of people are predicted to die from antimicrobial resistance within a few decades."

By bringing together a comprehensive database of bacterial strain genomes, including those indicating their virulence and resistance, and marrying it with clinical data via big data analytics, Palsson believes models can begin to provide information important for patient care.

One example he gives is urinary tract infections: his group previously found genetic signatures of E. coli can indicate which infections are more likely to progress to sepsis - in other words, the strains that have the molecular tools to stick to the bladder, cross tissue barriers and reach the bloodstream. In principle, those gene sets could become biomarkers to flag high-risk infections early and escalate care sooner for a better outcome for the patient.

Palsson is exploring the commercial potential in this approach, as well as leading a $4.1 million subcontract for a Defense Advanced Research Projects Agency (DARPA) project (via prime contractor CFD Research Corporation) to build and apply a whole-cell "digital twin" model of E. coli. The hope is the digital twin will be used to predict how E. coli responds to antibiotics and how to combat resistance. In addition, the digital twin will be applied to designing a strain to produce valuable chemicals from plant biomass byproducts.

Adam Feist and Ciara de Venecia stand in front of one of "the microbe evolution machines" in the Palsson lab at the UC San Diego Jacobs School of Engineering. (Photo by UC San Diego Jacobs School of Engineering/David Baillot)

A legacy of leaders

Palsson is consistently listed as among the world's most cited researchers by Clarivate's Highly Cited Researchers (based on Web of Science data), having amassed over 137,000 citations and shaped the field of integrative computational biology. He has been a member of the National Academy of Engineering since 2006 and was elected to the National Academy of Inventors last year.

But when you ask Palsson what he is proudest of, it is not any of those honors or even a specific breakthrough or successful company. Instead, it is his human legacy.

"I think it's my students, actually," he said. "I had my 40th anniversary as a professor the other day. We had a celebration on the 40th floor of the Hyatt downtown. The event was called 40th on the 40th. About 120 of my 150 PhDs and postdocs showed up. I realized that many of them have been incredibly successful commercially or academically.

"My students have done remarkable things, and that's really where the legacy of a professor lies."

Palsson is celebrated by mentees on the occasion of his 40th anniversary as a professor. (Photo by Marc Abrams)

To learn more about Palsson and his work, visit the Systems Biology Research Group Lab webpage.

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