I made this quick little illustration after being inspired by yesterday's Nobel Prize announcement. What I love about nature's solution to oxygen sensing is that we make a protein nonstop just to promptly and unceremoniously destroy it, trading this apparent wastefulness for the opportunity to react at a moment's notice to a lack of oxygen. This makes sense considering that oxygen is, obviously, crucial for life. So when oxygen is abundant, an oxygen-containing tag is added to HIP1alpha, which triggers VHL to target it for destruction. When oxygen levels drop, the tag cannot be added and so VHL doesn’t recognize it. HIP1alpha then stealthily travels to the nucleus where it turns on genes that effectively sound the alarm bells, increasing red blood cell production and more. Many thanks and congratulations to Dr. Kaelin, Dr. Ratcliffe and Dr. Semenza for uncovering nature's exquisite solution to responding to a lack of oxygen.
It is a rare treat to get the opportunity to honor a truly remarkable person who has incidentally played a role in your own story. Cathy Drennan was not only a cheerfully supportive member of my thesis committee when I was a graduate student, she was also one of my earliest clients. In 2011, when I was still teaching and getting O’Reilly Science Art off the ground, she hired me to make several illustrations for her HHMI-funded teacher training materials on diversity and stereotype threat. That led to another project creating graphics and animations for her Behind the Scenes at MIT project, a series of 2-minute videos featuring an MIT grad student, post doc or professor describing their research at a level that could be understood by freshman chemistry students. This project was a huge boon to my early career and perfectly dovetailed with my day job of teaching general chemistry to college freshmen.
So, when Cathy’s husband contacted me this summer about making a poster for her 20-year lab reunion I was thrilled. The hardest part was choosing from the dozens of protein structures her lab has solved using X-ray crystallography over the past 20 years. I decided to arrange them in chronological order according to when the structures were solved, and because of the lab’s focus on metalloproteins, I let the metals provide the light source so that the structures were like lanterns illuminating the long and winding path from 1999 to 2019.
So here’s to 20 more years of illuminating work in the lab and in the classroom, and if you want to hear Cathy talk about how growing up with dyslexia didn’t get the better of her insatiable desire to learn, you can listen to this story from last week on WBUR.
A couple of years ago I got a bee in my bonnet about making a stop motion animation (see August 2, 2017 post from this blog), and ever since then I’ve had an idea brewing. I’ve long believed that the very act of creating a scientific illustration or animation is an exercise in challenging one’s assumptions about their model and generally thinking about their science in a way they may not have had to before. I feel so strongly about the utility of this that I want to work with scientists to help them create their own animations to describe their work. Stop motion animation is perfect for this because it doesn’t require any artistic talent or mastery of any software. With a phone, a free app called Stop Motion Studio, and some clay, colored paper, or random detritus you have lying around, anyone can do this.
So the book trailer below was largely a professional development project for me, and one thing that I learned is that while stop motion can be a little painstaking and tedious, it is exactly the sort of activity that leads to the “flow” state that you keep hearing about. I imagined that as you animate your science, you spend time thinking about each step just that much longer while giving your brain a chance to wander a little. It’s the getting-ideas-in-the-shower effect.
Don’t worry, I still happily make journal covers, publication figures, business as usual, etc. But I want to add this to my list of services and I hope I will begin to mount evidence to support my hypothesis that creating animation can advance science in unexpected ways. Also, it’s fun, would make a great team-building activity for a lab, and at the end of the day you have an animation you can use in your talks, put on your website, and even include in your supplemental information.
Bill Murray’s ominous premonition aside, animal metaphors have been invading my work. Here, a quality control phosphatase (beagle) surveys Protein Kinase C (armadillo). Alexandra Newton’s lab showed that if Protein Kinase C relaxes its compact conformation, its phosphate (tennis ball) will be plucked off and the kinase will be rapidly degraded. Important because more beagles and fewer armadillos correlates with decreased survival in pancreatic cancer.
And next, when the client says that you can make the cover whatever you want, but by the way, the first author really really likes cats, this is what happens. Josh Figueroa’s lab showed that ligand exchange in a cobalt complex proceeds via an associative mechanism. In other words, if the leaving ligand left before the new ligand joined (or if the orange cat poised to jump leaves before the black cat gets there to take its place), the whole thing becomes too unstable.
I took a project for the Amazon Alexa science blog, largely to try to impress the hubs (totally worked). But it was great fun and a nice way to hone my After Effects chops a little. There will be more of these.
Happy New Year! I realized that I haven’t been posting many updates here because I’ve moved more toward using Instagram for that (@oreillyscienceart). This year I resolve to restore some loyalty to my website, starting with these two images that I made to highlight a recent Nature paper from the Chun lab at the Sanford-Burnham Prebys Medical Discovery Institute. Genomic Mosaicism is a phrase used to describe the fact that neurons from the same brain don’t necessarily share the same DNA sequence. (I was delighted to use this as an excuse to create a mosaic image.) The authors of this paper reveal that a major contributor to this mosaicism is scrambling of DNA sequences through homologous recombination. They envisioned it as a gene bursting out to produce thousands of different variants of a single gene, resulting in an explosion of genetic diversity. By studying this phenomenon in the context of APP, a protein involved in Alzheimer’s, they find a correlation between the extent of scrambling and the onset of Alzheimer’s disease. They also make the enticing discovery that reverse transcriptase is responsible for the scrambling events. That’s right, the same reverse transcriptase that we already have approved drugs for. Another intriguing anecdote is that it is very rare for people being treated for HIV with reverse transcriptase inhibitors to get Alzheimer’s disease. Hopefully testing of these drugs in the context of Alzheimer’s disease will begin soon.
Somatic APP gene recombination in Alzheimer's disease and normal neurons.
Lee MH, Siddoway B, Kaeser GE, Segota I, Rivera R, Romanow WJ, Liu CS, Park C, Kennedy G, Long T, Chun J.
Nature. 2018 Nov;563(7733):639-645. doi: 10.1038/s41586-018-0718-6. Epub 2018 Nov 21.
My Bauhaus-inspired cover came out in JACS last week. It’s about a protein chimera composed of a mutagenesis agent hitching a ride on an RNA polymerase to make mutations in specific genes. It reminded me of teenagers hanging out of the windows of moving cars, hitting mailboxes with baseball bats. (This metaphor probably dates me) In this case, the Shoulders Lab at MIT was clever enough to assign the teenagers (the mutagen) to a specific street. This image was made entirely on my iPad, which was a refreshing departure. Special thanks to George Howell Coffee in Newton, whose counter was the perfect height for drawing.
This cover design actually came up back in August when I was being interviewed by Carmen Drahl of Chemical and Engineering News at the ACS Boston meeting (seen here).
Obviously I didn’t say anything about the paper that hadn’t come out yet. She asked what my illustrations looked like, and I was explaining that the styles of my projects can vary dramatically. Even within this project, the other design we submitted for consideration for the cover was something much more typical of previous JACS covers (seen below). I was pretty surprised that they chose the wild card.
I had a nice surprise recently when this cover I made for Jacob T. Robinson's lab at Rice University came out. I didn't even know it had been chosen. It’s about immobilizing hydra (not the Marvel comics one) in a microfluidic device so its neurons can be poked and prodded. These little creatures are so cool. They stick to something at one end and then wave their little tentacles around, like a microscopic wacky wavy inflatable tube man. Or even better, like Dee from It's Always Sunny when she learns some new dance moves from one.
Once again, I was faced with the task of trying to convey both the macroscopic and molecular in one image. The last time I talked about this (two posts ago), I used a combination of 2D and 3D. This time on the molecular level I needed to show structures of polymers, highlighting the halogen bonds (the cracks in the wall as well as the theme of the issue). On the macroscopic level I needed the metal balls grinding together two different polymers that would then crystallize into a co-polymer in the solid state (that's a thing!?). So, I decided to use shadows, the idea being that by imagining a light source very low and close to the crystal, I could exaggerate the shadow size and show the molecular details of the halogen-bonded polymers. Obviously I took a little artistic license with the shadow of the powder falling into an atom, but that's what journal covers are for.
Shortly after this project, I discovered Vincent Bal, who makes drawings from the shadows of everyday objects, incorporating the objects into the picture. I highly recommend checking these out unless you are an artist and you don't want to look at something that's going to make you want to quit forever, because they are that good:
This illustration was done for a paper about paneth cells de-differentiating into stem cells. A sort of paradigm in stem cell research until recently was Waddington’s concept of the ‘epigenetic landscape’, which depicts cells rolling down a hill as they differentiate from stem cells to their terminal cell types. It was long believed until recently that cells could not reverse this process, or roll back up the hill. In the paper this image depicts, the authors demonstrate that activation of the Notch1 pathway directly or via irradiation induces Notch-dependent acquisition of a stem cell-like transcriptome. Like Sisyphus pushing his rock up the hill, Notch is seen here pushing the Paneth cell back up the ‘epigenetic landscape’ to a de-differentiated state with stem cell features. Taken together these results suggest that Notch may play an important role in the Sisyphean task of intestinal epithelial cell regeneration, particularly in cases of inflammation or injury.
As my first attempt at Zen doodling I can tell you there was nothing Zen-like about it. But I learned a lot about making these and I would love to do more, with enough time. As an aside, the black and white version made great coloring pages for my kids. It occupied them for at least five minutes. No, I don't think they achieved "flow".
One of the great benefits of having moved back to Boston almost a year ago is that I've been able to reconnect with old grad school friends, one of whom hired me for this cover art project. It's about using mRNA sequencing to monitor yeast fermentation, reporting back when the system is low in some key component such as, in this case, lipids. The idea for this image was conceived of most pleasantly over sandwiches on a roof garden in Kendall Square, as opposed to my usual forehead-to-desk-alone-in-my-office method.
One challenge that comes up in the majority of my projects in the problem of scale. How do you represent objects that differ in scale by several orders of magnitude together in one image? Sometimes artists will use a magnifying glass, or even just an inset. Sometimes I will use extreme perspective. For this project I decided to try something new, and used 2D for the molecular and microscopic, while using 3D for the macroscale objects. It's meant as a sort of wink to the audience, as in, I know mRNA is not as big as a computer monitor but I put it in a different dimension so it's okay, see? Like a parallel universe! Will you allow it?
What are the odds that while working on a project creating an image of a bacterial cell wall, I would come down with pneumonia? (It was back in November and I'm fine now.) Which is how this henceforth became known as the pneumonia project. And it is why I had to complete it largely in bed, using my iPad to "paint" it. But I actually liked it much better than how it was shaping up in my fancy 3D modeling program, so, thanks pneumonia.
I am definitely the one with the shoe untied and backpack unzipped. The hiking metaphor here is about varying levels of fitness for viral proteins accomplishing the task of protein folding. The fittest don't need any help from chaperones, while some are so unfit they get degraded before they even try folding. The idea for the hiking metaphor came from the first author of this paper, Angela Phillips, from Matthew Shoulders' lab at MIT. This was her original sketch for the concept:
In other news, we managed to have the O'Reilly Science Art holiday party of two this year. After a beer at the Cambridge Brewing Company, which I hadn't been to since I defended my thesis *mumblemumble* years ago, we saw Ladybird at the Kendall Square cinema. Because I am the boss. Or because the only showing of Star Wars The Last Jedi we could see started too late.
This painting came home from Kindergarten, and I was overcome with envy at this display of immune cells. Despite the fact that he had no idea that he was painting cells, I'd been out-science illustrated by my five year old, and so I thought this warranted a guest post by him again.
Otto Warburg was a Nobel Prize-winning German biochemist who championed the hypothesis, which we now know as the Warburg Hypothesis, that cancer is caused by cells switching from the respiration of oxygen to the fermentation of sugar. This was in 1924. This criteria has largely been relegated to a correlation, since with the advent of molecular biology we learned about mutations in DNA. It has been a controversial topic, and for what it's worth, there has been a 10-fold increase in articles related to the Warburg Effect over the past ten years.
In this study (see reference below image), the authors link yeast cell fermentation to the oncogene Ras. They not only correlate an influx of glucose with accumulation of fructose 1,6-bisphosphate and activation of Ras, they show that fructose 1,6-bisphophate triggers activation of Ras. This supports the Warburg Effect within the modern context of at least one way in which we understand cancer to work. The image here incorporates glucose, fructose-1,6-bisphosphate, proliferating cells, and Ras into a portrait of Otto Warburg. Only after the completion of this illustration did I realize that he studied chemistry under Emil Fischer, known among other things for drawing sugars in, that's right, Fischer projections. Had he studied under English chemist Sir Norman Haworth then it would have been apropos indeed. So it goes.
Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras
Ken Peeters, Frederik Van Leemputte, Baptiste Fischer, Beatriz M. Bonini, Hector Quezada, Maksym Tsytlonok, Dorien Haesen, Ward Vanthienen, Nuno Bernardes, Carmen Bravo Gonzalez-Blas, Veerle Janssens, Peter Tompa, Wim Versées, and Johan M. Thevelein
Nat Commun. 2017; 8: 922.
Published online 2017 Oct 13. doi: 10.1038/s41467-017-01019-z
This week a paper came out in Science Translational Medicine that describes the use of hematopoietic stem and progenitor cells to treat Friedrich's Ataxia. Once they differentiate into mature microglia (see in yellow), they can actually transfer proteins that are missing in Friedrich's Ataxia to the host's cells. They also differentiate into other cells in other parts of the body to deliver these rescue proteins as well. Pretty amazing stuff. I made this image for the Cherqui Lab at UCSD, the authors of the study, and you can see the image (for now anyway) as the second in the scrolling banner images on both the Science Translational Medicine and Science homepages:
The Lavis Lab found that adding the four-membered functional group known as azetidines to the classic rhodamine dyes makes the brighter and more photostable. Even cooler, they found that by functionalizing the azetidines they could fine-tune the properties of the dyes, and gave them a whirl in cells too.
The October installation of the Art of Basic Science is in the works. More soon!
This installment was inspired by the editorial illustrations of Rob Dobi (though this looks nothing like his), and the following paper from JACS, wherein the authors describe a cubane-based water oxidation catalyst. It is capable of oxygen evolution, a key component in artificial photosynthesis, which is a key component in playing nice with earth.
Manganese-Cobalt Oxido Cubanes Relevant to Manganese-Doped Water Oxidation Catalysts.
J Am Chem Soc. 2017 Apr 19;139(15):5579-5587.
Alex Taylor of C&E News wrote this lovely piece about my path to scientific illustrator (click on image to go to full article), and as a result I have received some very nice e-mails from Ph.D. students who have been inspired by it. This was exactly the effect I hoped this article would have so I was delighted, but I also imagined that many people may have read this and wondered how feasible it really is to make a living doing this, and so I want to give the full story.
My annual income is in the ballpark of a postdoc salary, without the guaranteed monthly check (but also without the grueling hours). Having the safety net of a very supportive husband with a full time job has been key to this all going so swimmingly. Part of the reason for quitting teaching, in addition to the fact that I was having to turn away illustration work, was that it's hard enough to do two things well, but I found it nearly impossible to do three things well. So, when our first son was 18 months old, we looked at our finances and decided we could do it. And now four years later, with two kids aged 2 and 5, I'm very grateful for the flexibility this career allows. I am keenly aware that although I have worked very hard and made sacrifices for this career, I am lucky. It would have been much more of a struggle without the second income, and I thought that aspiring science illustrators ought to know that too. Freelance is not for the faint of heart, but I will say that at this point, I do not do any marketing, and I am simply fielding requests. I believe it would be more lucrative if I was more proactive, but I am steadily getting exactly the amount of work I want right now. This isn't due to a lack of ambition, but rather the constant fine-tuning of the ever-elusive work-family balance.
That said, there are other more stable jobs in this industry than freelance. There are illustrators and illustration editors for scientific journals, graphic designers for biotech companies, scientific animation studios, textbook illustrators and much more. To help pave the way to some of these, there are masters programs like the Master of Science in Biomedical Visualization at the University of Illinois-Chicago, the Master of Science in Biomedical Communication at the University of Toronto, the Medical and Biological Illustration graduate program at Johns Hopkins, and the Graduate Certificate Program in Science Illustration at CSU Monterrey Bay. You can also learn programs like Illustrator and Photoshop, and even 3D modeling and animation programs like Maya and 3D Max, with a very reasonably priced subscription to Lynda.com. And if anyone would like more advice feel free to ask.
For the latest installment of this series, my first attempt at stop-motion animation. It's pretty low budget!
Extensive horizontal gene transfer in cheese-associated bacteria. Bonham KS, Wolfe BE, Dutton RJ. Elife. 2017 Jun 23;6. pii: e22144. doi: 10.7554/eLife.22144.