The 3rd Dimension

The 3rd Dimension

BTI Researchers test 3-D printing technology to scale up—and down

Since it first appeared on the market in 1984, 3-D printing technology, also known as stereolithography, has been used to create everything from robotic aircraft to artificial limbs. The technology caught the attention of the media this summer, when reports surfaced that a Canadian man fired 14 shots from a rifle manufactured on a 3-D printer using a design downloaded from the Internet.

The cost of the technology is becoming more affordable—desktop units now range from $250-$2500—and the printers are finding their way into artist studios, research labs, and in some cities, the local Fedex/Kinkos copy shop.

In 2012, BTI members Brett Barney (BTI/Department of Bioproducts and Biosystems Engineering) and Igor Libourel (BTI/Department of Plant Biology) approached BTI director Mike Sadowsky for funds to purchase a MakerBot Replicator 2—a low-cost 3-D printer about the size of bread box. Both saw the potential to advance research and training goals but each had a novel approach to experimenting with the technology.

Barney immediately saw the potential of the technology in the classroom and has created brightly colored, hand-painted models to help explain cell metabolism and metabolic pathways to his students.

Beginning with three dimensional images of proteins from the Protein Data Bank, a repository of structural images for large biological molecules, he uses a variety of

3-D rendering tools to refine his models and build the scaffolding required to support the structure as the printer lays down layer upon layer of ASB thermoplastic, similar that found in Lego® building blocks. After cutting away the scaffolding and the excess material, the molecular models are painted, polished and ready for display.

The initial models took up to 15 hours to print, with several additional hours of detailed work for clean up and finish. With practice, he was able to reduce the printing and clean up cycle to a couple of hours. Once the models are complete, Barney posts the plans, with photographs and annotations, on Makerbot’s open-source repository called Thingiverse. Published under the name MoleculeMaker, Barney’s model of the FeMo Cofactor is available for download by members of the online community.

Barney hopes to print a full model of a photosynthetic reaction center, but also builds partial models to highlight unique characteristics of the molecules he studies. In fact, his lab has used the models to help predict sites for mutagenesis studies in wax ester synthases—enzymes important in the effort to produce biodiesel from a complex biomass such as cellulose. Barney recently published the
results in the Journal of Applied and Environmental Microbiology.

For more about Barney’s 3-D Models see: 

Rapid prototyping and development of miniature bioflow reactors

With an eye toward understanding environmental changes brought about by global warming, the Libourel Lab studies metabolic features of Ostreococcus, a picoalgae genus common in the world’s ocean. Investigating the relationship between metabolic adaptation and climate models, the lab relies on bioflow reactors to manipulate and monitor the organism’s response to evolutionary pressure.

After modifying bench scale reactors with customized hardware and software, Libourel and his students realized they could achieve the same results, using fewer resources, by scaling down. But each bioreactor requires a custom enclosure, which can cost as much as $500 to produce, increasing cost and slowing development. Using the Replicator 3-D printer, Libourel hopes to construct and modify the enclosures which house the circuits, pumps, and fans required to run the reactors. In addition to the cost saving, the rapid prototyping and development will allow the lab focus on what’s happening inside the dish instead of the box.

BTI’s Wei-Shou HU spearheads new consortium to speed drug development from Chinese Hamster Ovary cell lines

Distinguished McNight Professor Wei-Shou Hu (BTI/CEMS) is leading a new Consortium for Chinese Hamster Ovary Cell Systems Biotechnology formed under the auspices of the Society of Biological Engineering. This new consortium of seven pharmaceutical companies from USA, Europe and Japan is built upon work of the proceedings of the Consortium of Chinese Hamster Ovary Cell Genomics from 2006-2010, which completed sequencing of the Chinese hamster genome and developed platforms for genome scale analysis.

The Chinese Hamster Ovary (CHO) cell line is used in the production of over 70% of all biologics, valued at over $40 billion per annum.  The new effort aims to harness the genomic information and further advance our understanding of cell line production, productivity and product quality and to facilitate member companies entering the post-genomics era of biologics manufacturing.

Gary Muehlbauer named distinguished McKnight Professor

BTI member Gary Muehlbauer, was recently named a Distinguished McKnight Professor. This award is granted to outstanding faculty members who have recently made the transition to full professor status. Muehlbauer is head of the Department of Plant Biology, and is also a part of the Department of Agronomy and Plant Genetics. His research is concentrating on wheat and barley and molecular genetics, as well as integrating genomics resources into barley breeding programs. Highest regards to Gary Muehlbauer.

Kechun Zhang joins the BioTechnology Institute

Kechun Zhang

BTI/Chemical Engineering and Materials Science BTI welcomes Kechun Zhang, Assistant Professor in the Department of Chemical Engineering and Materials Science. Zhang completed his PhD in chemistry at the California Institute of Technology and his postdoctorate fellowship at the University of California, Los Angeles. Zhang’s research focuses on the sustainable production of biofuels, chemicals, and biologics through engineered processes including protein evolution, metabolic flux, and the design of artificial metabolic pathways. In 2013 Zhang was the recipient of the 3M Non-tenured Faculty Award and the American Heart Association National Scientist Development Grant Award.

Yeast study yields insights into origin of multicellular life

Yeast study yields insights into origin of multicellular life

Researchers in the BioTechnology Institute (BTI), lead by faculty member Michael Travisano, have demonstrated how multicellular organisms can evolve from single-celled individuals. This important transition has long been a mystery to scientists. The researchers showed that the ability to cluster and the ability to live together cooperatively in groups were key steps. This research not only yields new insights on multicellularity, but also may improve understanding about the processes of aging and the development of cancer.

The Travisano research group has been looking at yeast clusters in the model system Saccharomyces cerevisiae, more commonly known as baker’s yeast. Through careful harvesting of yeast cells that settle at the bottom of a test tube after mild centrifuge, they have been able to select for multicellular strains that form snowflake-shaped clusters.

Multicellular yeast display primitive division of labor, one of the requirements of multicellularity. To reproduce itself, a small portion of the snowflake breaks off at “breakpoints” created by apoptotic cells (highlighted above in green) and then grows. In this regard, there is a division of labor – some cells serve as the progenitors of another cluster and some cells die to allow other cells to separate. (photo courtesy Michael Travisano and

In a study recently published in the Proceedings of the National Academy of Sciences (PNAS), the researchers demonstrated that clustering of the yeast cells was adaptive and that beyond simply clustering, cells within these colonies, though physiologically similar, evolved different functions and traits. In particular, improvements in colony reproduction were achieved by a process called apoptosis.

“Arguably one of the most important traits in existing multicellular organisms is apoptosis,” explained postdoctoral research associate Will Ratcliff, first author on the paper.

Apoptosis is the genetically programmed death of a cell that is critical for multicellular development and maintenance. Unlike traumatic cell death caused by injury, apoptosis occurs as a response to biochemical changes in the cell. Through microscopic observation of the multicellular snowflake-shaped yeast clusters, the team found that dead and dying cells formed weak links that provided break points for separation of a daughter cluster. This genetically programmed death thus promoted multicellular reproduction.

“It’s a structural interaction,” observed Travisano, “caused by cell death that aids reproduction.”

Though reproduction of individual yeast cells can be either sexual (through the production of spores) or asexual (by means of cell division), the multicellular reproduction of the newly evolved yeast colonies was asexual. The structural breaking off of new smaller colonies, though not characteristic of multicellular animals, is a strategy found in plants and was facilitated by increased apoptosis. This asexual reproduction of multicellular yeast also presents researchers with some insights into the aging process (progressive cell damage and death) and into the unregulated development of cancer cells.

“It’s a model of a cancer tumor,” concluded Ratcliff. “There are a lot of similarities to how we think cancer might occur and evolve.”

Read more about the multicellular yeast project on
Read the University of Minnesota news feature.
Read the Minneapolis Star Tribune feature.

-Tim Montgomery