In late February 2019, the National Science Foundation (NSF) gathered a group of scientists from widely different disciplines who rarely communicate—let alone collaborate—into one room, provided skilled facilitators to push their ideas to the edge of innovation and stepped back to see what would happen.

“Ideas Labs” like these undergird the NSF’s $36 million dollar investment in its Understanding the Rules of Life portfolio aimed at accelerating development in two key areas of science and engineering research: building a synthetic cell and epigenetics.

According to Cheryl Kerfeld, MSU Hannah Distinguished Professor in the MSU-DOE Plant Research Laboratory and Department of Biochemistry and Molecular Biology who attended this particular Ideas Lab outside of Washington, D.C., what happened was akin to the “wheel” people getting together with the “suitcase” people—a breakthrough.

Kerfeld will lead this unlikely team of scientists that includes five research groups from universities across the nation in a $3.4 million Rules of Life grant to engineer a synthetic cell.

“We are going to take building blocks from different scientific disciplines that would never naturally get together—physics, biology and materials chemistry—to build a functional, multi-compartmental and fat-free cell, or ‘ProteoCell,’” Kerfeld said. “Outside of the Ideas Lab context, we never would have self-assembled into a team, and it never would have occurred to me to build a cell without lipids.”

Classically, all cells are composed of the four basic macromolecule groups: proteins, carbohydrates, DNA and the fats, or lipids. 

“The lipids make up the boundaries of individual cells and their internal compartments—known as organelles,” Kerfeld explained. “But those lipids are not directly encoded by your genome, so we have little control over them, and this presents a fundamental challenge in building synthetic cells.”

The Ideas Lab took this challenge out of the equation with a simple question. Are lipids necessary?

With years of research on bacterial organelles under her belt, it was a question that Kerfeld’s lab was poised to answer. Until recently, the prevailing distinction between eukaryotes, like humans and plants, and prokaryotes, like bacteria, was that bacteria lacked the organelles to perform discreet activities.

Kerfeld’s lab has prominently contributed to the knowledge that bacteria do indeed have organelles, only they are made entirely of proteins. 

“Instead of using lipids, we are going to take the ‘membrane’ of bacterial organelles, programmable proteins, and test the limits of their potential for composing organelles and even the cell membrane itself,” Kerfeld said.

Although the first and fundamental goal of the project is to make a synthetic cell without lipids, the project also has significant implications in the production of biomaterials and biofuels in the United States.

“When industries try to use cells as factories for renewables in the bioeconomy, one of the big problems is bioseparation, or getting the product away from the cell material,” Kerfeld said. “If we can engineer cells made of only three macromolecules, it will be simpler to recover product. This is one way that free cells could have a tremendous impact on human health, sustainability and the environment.”

Kerfeld’s Rules of Life team members are: Christine Keating, professor of chemistry from Penn State University; Millie Sullivan, professor of chemical and biomolecular engineering from the University of Delaware; Vincent Noireaux, professor of physics from the University of Minnesota; Giovanna Ghirlanda, professor of chemistry from Arizona State University; and Barbara Harthorn, professor of anthropology from the University of California Santa Barbara. 

“There are important and introspective questions that need to be asked as we develop new technologies,” Kerfeld said. “A cell without lipids is highly artificial, and if we are successful, it may lead to a self-propagating system that could be harnessed for industrial applications. There are ethics around this as well as the fundamental questions that we are asking, like what is life?”

With NSF’s encouragement and support, the team will also study the societal perceptions of a synthetic cell as well as how engineering a new kind of cell might also change the scientists.

“The NSF’s Rules of Life is one of the grand challenges of biology,” Kerfeld noted, “and MSU should be proud that we are leading an elite group of high caliber researchers and faculty able to address these questions.”