Two New Directions in Synthetic Biology

New online articles this week highlight two forays into the world of synthetic biology. Each, in its own way, gives a different perspective on how sophisticated the field has become in the past few years, since smiley-face DNA was first introduced.

Prof. Benjamin Geiger of the Weizmann Institute and Prof. Joachim Spatz of the Max Planck Institute for Intelligent Systems, Germany are leading an unusual collaboration. One is a biologist, the other a materials scientist. Together, they are working on models that incorporate the whole gamut from completely man-made materials to 100% biological cells. In between, they are creating synthetic cells – artificial lipid membranes with a handful of proteins added in.

The idea is to create a basic research model to study cell adhesion on various substrates. Cells are constantly checking their environment – continually assessing the surfaces they touch and deciding whether to adhere to those surfaces or pull up their adhesion complexes and move on. According to Geiger, scientists pretty much have the “grocery list” of which proteins are involved. But it is hundreds of proteins long – an extensive inventory of ingredients with no recipe attached. So Geiger and Spatz are looking for a way to recreate the recipe from the mixing bowl up: Adding a few proteins at time into their synthetic cells, they hope to understand which must come together for the basic process to occur, and which are enhancements and adjustments to the original formula.

Of course much of human biology – growth and development, and cancer metastasis are the big ones – rely on these sensing and adhesion mechanisms, but Geiger and Spatz bring up some others: How certain cells sense blood flow, for instance, might affect the sticky buildup of plaques on artery walls. And they suggest that even before primitive cells began sticking together to form multicellular organisms, they probably formed some version of these complexes to adhere to other things – food sources, for instance.

The second article describes the postdoctoral research and future plans of Dr. Sarel Fleishman, who recently joined the Institute. Fleishman was in the protein design lab of Prof. David Baker at the University of Washington, Seattle, where he designed a protein that is able to block a wide range of flu viruses.

“Designed” is the operative word here: Fleishman and his lab mates showed that one can predict what is needed to selectively bind to a virus protein’s active site, create a detailed plan for a new protein structure to carry this out, and then actually shape that new protein according to plan on an existing protein base and even test it to see if it works. (Clearly, this one-sentence description makes it sound a lot simpler than it is.)

Geiger and Spatz have been moving toward synthetic cell adhesion models for several years – beginning with putting live cells on precisely designed synthetic substrates to see how they react. So the synthetic cells, in one sense, are the next logical step in their investigations. They are betting that this step will be a significant one, however, and the European Research Council is laying down bets too, in the form of a hefty grant.

Fleishman is now putting together his lab at the Institute. The protein he designed in his postdoctoral research is already on its way from the basic research bench to pharmaceutical R&D. We can’t tell you what the next protein to come out of his new lab will be, or even whether the designer anti-flu protein will eventually end up on pharmacy shelves. But we can tell you that this is just the beginning.

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