At the edge of life

Synthetic organic chemist Kate Adamala develops cell-mimicking systems with just the right amount of complexity.
September 27, 2016

“[I’d like to] see if we can actually model life, figure out the principles guiding evolution, understanding evolution better and the emergent properties of cells to build a universal model for how biology works.”  

It's not easy being a cellular biologist. Try to study molecules and what they do in an intact cell, and you end up with so many variables and cascades of interaction that it’s impossible to figure out what’s going on. But take the cell apart to try to understand the roles of individual components in making its internal clockwork tick, and you end up with bits and pieces that don’t work as they do when intertwined within a living system.

Enter Kate Adamala. A new assistant professor in the Department of Genetics, Cell Biology, and Development, Adamala has developed an experimental system at the sweet spot in between intact cells and individual biochemical pathways — the “Baby Bear” version of experimental cellular systems, in Goldilocks terminology. Neither as complex as living cells nor as reductionist as individual molecules, Adamala’s “minimal synthetic cells” provide a not-too-complicated yet not-too-simple model for understanding how life operates at the molecular level.

Three years ago, as a graduate student at Harvard University, Adamala led an effort to develop the first system that can synthesize RNA without enzymes in model “protocells” — artificial constructs with some characteristics of living cells. The approach she pioneered in the process holds huge promise as a tool for doing everything from understanding how life formed to building microscopic factories for producing individualized medicines.

“The benefit is, we get to study a particular pathway without interference and noise from other pathways in the rest of the cell,” she says.

Adamala’s interest in working at the intersection of chemistry and biology sprang from a childhood love of science fiction. Delighted to discover as she grew older that astrobiology was a real science and not just fantasy, she got involved in research aimed at figuring out what the first cell looked like as an undergraduate. That involved constructing protocells — and she soon recognized that the simplified systems she was designing and building could be used as a valuable tool for studying how living cells work.

One way Adamala is currently applying the approach is to study how proteins embedded in cell membranes take signals from outside the cell and use them to direct changes within it. She’s also exploring the chemical basis of biological processes, such as cell wall construction and mRNA splicing and maturation.

Since she joined the University of Minnesota in September, Adamala has been busy exploring opportunities for collaboration with researchers who see her synthetic cell-like bioreactors as a tool that will allow them to tweak — and so study the mechanism behind —  crucial cellular processes without just ending up with a pile of dead cells. “The work I’m doing is only relevant if I can transfer it to live systems, so I’m very happy about the possibility to immediately get into collaborations, if I develop a new tool,” Adamala says. She’s also continuing collaborations she started earlier with Department of Physics and Astronomy associate professor Vincent Noireaux to build increasingly complex cell-like systems, and she works very closely with Aaron Engelhart, another new CBS faculty member.

Looking forward, Adamala sees promise for applying her work to developing new therapies for human diseases and advance personalized medicine. One of the big challenges in drug development is that a new molecule can appear to do a particular job in a test tube, but once it’s in a living cell, it functionally crashes and burns. “So we’re trying to develop a system that will let people use the advantages of an in vitro system to screen for possible bioactive molecules in a system relevant to the actual natural cell,” Adamala says.

Adamala’s dream is to someday assemble a system from chemical building blocks that can grow and evolve on its own — sort of the missing link between a living cell and a machine that makes organic molecules.

“[I’d like to] see if we can actually model life, figure out the principles guiding evolution, understanding evolution better and the emergent properties of cells,” she says, “to build a universal model for how biology works.”  —Mary Hoff