Cover stories: Making the synthetic yeast chromosomes cover and introductory spread image

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Science  10 Mar 2017:
Vol. 355, Issue 6329, eaan1126
DOI: 10.1126/science.aan1126

Cover stories offer a look at the process behind the art on the cover: who made it, how it got made, and why.

The 10 March 2017 issue (Fig. 1) highlights a collection of papers describing the most current work done in pursuit of producing a synthetic, minimal yeast genome. It is now possible for 6.5 out of 16 chromosomes of Saccharomyces cerevisiae to be synthesized. This idea does not easily lend itself to photography or microscopy, so our challenge was to find a way to illustrate it, on both the cover (Fig. 1) and the introductory spread of the magazine.

Fig. 1 The 10 March 2017 cover.

For the cover, I harnessed a visualization method developed by one of the authors, Julien Mozziconacci. This technique uses data describing chromosomal contacts in a cell’s nucleus to reconstruct their conformation in 3D space (see http://dx.doi.org/10.1038/nmeth.3104). In a Research Article in this week’s issue, this method was used to compare the conformations of the synthetic versions of chromosomes against their wild-type counterparts within the cell nucleus. As I looked through this paper, I wondered what a hypothetical genome that had every possible synthetic chromosome to date might look like. To find out, Julien averaged the genomes of millions of yeast cells and supplied me with 3D coordinates describing the “path” that each chromosome might traverse. Next, I wrote a program in Python that instructed my 3D modeling software, Cinema 4D, to draw out those paths (Fig. 2).

Fig. 2 A snippet of the text file containing 3D coordinates, which Cinema 4D can interpret through a custom Python program.

What followed was the hardest part: How could I make a tentacle-like bundle of tubes look like the chromatin it actually represented? What would distinguish synthetic chromosomes from their nonsynthetic counterparts?

For viewers to interpret the cover image correctly, it was essential to incorporate the canonical structure of chromatin fibers. This is where another challenge presented itself: How would I accurately represent the scale of the fibers and approximate the correct number of nucleosomes per arm? I accomplished this by adding some controlled noise, effectively making a much longer, winding path for the nucleosomes to follow (Fig. 3).

Fig. 3 Fitting nucleosomes.

(Left) Coil representing the DNA that would be wrapped around a nucleosome. (Middle) Path for one arm of a chromosome. To accommodate the correct number of nucleosomes, I needed to create a new, much longer line that condensed to fit the original line. (Right) Close-up of the nucleosomes following the longer path. I could be economical with the details and reduce rendering time, as this level of intricacy would not be visible in the final illustration.

Last, I needed to work on the look and feel of the illustration. After multiple versions that conjured up images of tarantulas and aliens, I was not satisfied with the dark, “creepy” look of the cover. So I dared myself to do exactly the opposite of what I was doing—I made the image very bright and turned the model upside down—and that’s what worked. This cover was full of challenges but ultimately shows what you can attain when you look at hard science through a creative lens.

Valerie Altounian, Scientific Illustrator at Science

For the introductory spread (Fig. 4), we wanted to take another approach toward representing the 16 yeast chromosomes. After speaking with Jef Boeke, the director of the Synthetic Yeast Genome Project (Sc2.0), we decided to use a unique method developed by his team. This technique, known as “bioprinting” or “biopointillism,” is a process of printing nanodroplets of genetically modified yeast cells onto an agar plate. The genetically engineered yeast expresses genes for different pigments whose colors intensify over time. For more detail, see yeastart.org.

Fig. 4 Introductory spread image.

The biopointillism technique lends itself to the creation of very simple, high-contrast images. We decided to complement the realistic cover with an intro spread that has a more stylized and generic representation of the 16 chromosomes, with blue as the main color (wild-type yeast chromosomes) and yellow as an accent color (synthetic yeast chromosomes), matching the same accent color used on the cover for the 6.5 synthesized chromosomes (Fig. 5).

Fig. 5 A close-up view of the yeast colonies, printed to the shape of the 16 yeast chromosomes.Image printing by Jasmine Temple, Boeke lab, Institute for Systems Genetics, NYU Langone Medical Center; Photography by Drew Durian

We worked with Jef Boeke and his Assistant Research Technician, Jasmine Temple, to come up with the desired pixel resolution for the image. We supplied their lab with the final image design, which they subsequently printed with the yeast droplets. Each droplet is a colored strain of yeast. The result was an image printed with 24,576 yeast colony nanoliter droplets (Figs. 6 and 7). The yeast was then set to grow over the course of 2 weeks, which allowed the colors to deepen.

Fig. 6 A “canvas” of yeast emerges from the acoustic droplet ejection robot.

Droplets fly vertically from a well containing liquid cultures of yellow, blue, and black pigment, producing yeast onto an inverted petri dish.

Image printing by Jasmine Temple, Boeke lab, Institute for Systems Genetics, NYU Langone Medical Center; Photography by Drew Durian
Fig. 7 The agar plate of yeast cells.

The plates are 192 pixels by 128 pixels, printed with 24,576 droplets.

Image printing by Jasmine Temple, Boeke lab, Institute for Systems Genetics, NYU Langone Medical Center; Photography by Drew Durian

To finally present this collaboration between researchers and designers, Photo Editor Emily Petersen selected photographer Drew Gurian (www.drewgurian.com/index/G0000W_OWudIK5JE/thumbs), who is known for his brilliant portraits of musicians and entertainers. Gurian and his assistant had the challenge of photographing the bioprinted yeast chromosomes. Because he was aware of the final spread layout, Gurian used delicate lighting and darkened areas of the image to show the color prominence of the 16 chromosomes and allow for text clarity against a dark background.

Both the cover and intro images combine analysis and tools from the researchers with the creative thinking of our team here.

Marcy Atarod, Design Editor at Science

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