From extending lifespan to bolstering the immune system, the drug’s effects are only just beginning to be understood.
With strong foundations in both art and science, Ahna Skop has been able to capture the marvel of—and mechanisms behind—cytokinesis.
April 1, 2012|
UNIVERSITY OF WISCONSIN-MADISON, JEFF MILLER
As a kid, Ahna Skop ruled the science fair. “Every year I was in at least the top three, and I know I won grand prize once or twice,” she says. Not that her experiments always yielded the predicted results. “One time I was trying to figure out whether mice would go in a particular direction based on color,” says Skop. “My dad and I built a maze with different-colored walls and added a couple mice.” But her subjects had plans of their own. “They ended up breeding—a lot,” she says. So Skop had to figure out what to do with the 150 mice that resulted. “My dad said he’d pay me a dollar for each mouse I could get rid of,” she laughs. But she never made the full bundle. “I had to let some go in the backyard.”
Now an associate professor at the University of Wisconsin in Madison, Skop still loves experimental surprises. On her desk sits a Zen quote by artist Juan Gris: “You are lost the instant you know what the result will be.” Skop lives by those words. “I think you need to know a way to get to a result—but you shouldn’t know what you’re going to find,” she says. “Then you’d be biased, and you won’t find what you’re looking for, because it’s usually something you don’t expect.”
What Skop could not have expected was that her first talk as a graduate student, on the orientation of the mitotic spindle in dividing cells, would be given to an audience of 8,000, or that her microscopic images of cells caught in the act of splitting would be displayed in the Berkeley BART station and on a building in South Korea. Here she discusses how she identified 100 new proteins involved in cytokinesis, how she chatted about cat litter with George W. Bush, and how a food fight led her to a life in science.
I showed it’s not just trash, that there are things in the midbody that are important for spindle alignment and cell division. Now some people even consider the midbody a new organelle.
Worm party. In her sophomore year as an undergrad at Syracuse University in 1992, Skop was studying biology—and ceramics. That year the C. elegans meeting was in Madison, Wisconsin, and Skop was surprised to find that scientists like to have fun. “I didn’t know scientists could dance,” she laughs. “I’d read their papers—and here they were. Dancing! It really humanized science for me.” That and the food fight. “I don’t know if it was banana cream pie or coconut cream pie, but everyone was covered in it. I think it cost about $3,000 in cleaning supplies—and it was the end of the banquets at the worm meetings. But it was hilarious. And comforting. It made me realize: these people are just like me. They’re creative and fun. And I could be one of them. That’s when I knew I wanted to be a scientist.”
Starstruck. As a graduate student at the University of Wisconsin–Madison, Skop was initially intimidated by renowned worm biologist John White, the PI who would become her mentor. “I did a rotation with him, but I was too scared to join his lab. He was so famous, I got the jitters working next to him. I’d read his papers and I couldn’t believe this person would even talk to me! But that was my stupid naïveté. John White is the most humble, down-to-earth guy in science. Eventually I realized that his lab was where I needed to be and I switched. It was the best decision I ever made.”
Record crowds. In White’s lab, Skop was exploring how cells in C. elegans establish their cleavage plane—the axis along which they will divide. In her first publication, which appeared in Current Biology in 1998, Skop showed that dynactin—a protein that interacts with dynein motors—helps orient the mitotic spindle, which then specifies the plane where a cell will split. “That paper was a big deal, probably because it was one of the first to use double-stranded RNA to knock out gene function in C. elegans,” says Skop. “I was injecting sense and antisense RNA strands into the worm and getting a knockout effect.” And she presented the work to an audience of 8,000. “The room was huge. But it was fun! Turns out I prefer the bigger crowds, because people don’t usually ask questions. So it’s actually easier than speaking to smaller groups.”
Life-changing results. Skop went on to show that to complete cytokinesis animal cells have to send a fresh supply of membrane to the point at which the daughter cells will pinch apart. “I remembered reading about some experiments in algae where the cells were treated with brefeldin A”—a drug that inhibits membrane trafficking. In the algae, brefeldin A interrupted spindle alignment. In C. elegans, Skop found, the drug caused cytokinesis to fail. “The embryos tried to divide. They’d pinch in, but then snap back out. So whatever material is needed to separate those cells is no longer there”—a finding published in Current Biology in 2001. “In my postdoc I went on to figure out what proteins were in that little pinch point. And I’ve been working on them ever since. That two-day experiment changed my life.”
One man’s trash . . . As a postdoctoral fellow at the University of California, Berkeley, Skop isolated midbodies—that pinch point between dividing cells—from a preparation of Chinese hamster ovary (CHO) cells. “There are all these old papers from the late ’70s and ’80s about isolating midbodies from CHO cells to look for mitotic motors. So I e-mailed those researchers and they sent me their old protocols.” With a bit of tweaking, Skop was able to harvest midbodies and identify some 160 proteins that appeared to be unique to that structure. All that was left was to determine whether any of those proteins were important for cytokinesis. Using RNAi to knock out the corresponding genes in C. elegans, Skop tested them all. “I validated what came out of the proteomics assay, which no one had ever done before. And I found about 100 new proteins required for cell division in a structure that many people had dismissed as a garbage can. Prior to this study, a lot of people thought that when the cell pinched down, all the remnants of cell division—essentially a bunch of junk—got trapped there and destroyed. I showed it’s not just trash, that there are things in the midbody that are important for spindle alignment and cell division. Now some people even consider the midbody a new organelle.”
Front-page news. Fluorescent images from Skop’s study of the midbody made the cover of Science in 2004. “I almost peed my pants,” she says. “As an artist, that was the best thing. It was like getting a painting in the Louvre. On top of that, Science has used that cover in a lot of their marketing. So I have a baby Einstein holding my Science cover. And there’s Isaac Newton holding it, too. A friend ran up from the Berkeley BART station to tell me she saw my cover there. It was also in the San Diego airport and on the streets in London. A former undergrad was in South Korea and said it was displayed down the side of a building in Seoul.
Elegans art. Since her grad school days some 15 years ago, Skop has been curating the biennial Worm Art Show—a highlight of the international C. elegans meeting. “The first year, there was a scientist/glassblower who etched part of the worm genome on the side of a vase. It was amazing. And it’s been like that every year. There have been watercolors, leather belts, knitted worms, and a driftwood mobile that looked like larval worms. People love the show, and it’s even been good for my career. I’ve been introduced in past job interviews as the girl who does the art shows and who also does good science.” It’s also given her a leg up on the “broader impact” section of her NSF grants. “I think a lot of scientists find it hard to do outreach,” she says. “But for me it’s very, very easy. Because it’s part of who I am.”
When I found microscopy, I realized it was the bridge I was looking for between arts and science.
Paying it forward. “I’m part Cherokee Indian and I do lot of outreach with the Native American communities. I’ve always loved mentoring students, and I wouldn’t be here today if someone hadn’t taken me into their lab. So it means a lot to me to be able to give back, to get other students excited about science.”
Two cultures. “I enjoy doing things that are creative. It brings me back to my core, to my home, to who I really am inside. Microscopy is very visual. If I hadn’t discovered video microscopy, I probably wouldn’t be in science. Running a gel and doing things with DNA doesn’t really turn me on. Microscopy was the bridge I was looking for between arts and science. And I’ve been able to use my love of microscopy in my outreach. Many kids get turned off by science because they never see how amazing it looks.
Secret signal. “Cytokinesis has been studied for over 150 years and still no one knows: what is the signal for division? What is the molecule that comes from the spindle and goes to the plasma membrane, causing it to pinch in? That’s the big unanswered question. No one knows, but a lot of people are looking. Anyone who finds the signal for cytokinesis will get a Nobel Prize for sure.”
Forward with caution. In the late 1990s, Skop experienced a serious case of electronic embarrassment. “I had forwarded this joke I’d barely read to a friend—and then realized that I’d sent it to every faculty member in my program.” Skop was red-faced, to say the least, but she did learn something interesting about science culture. “Different departments have different senses of humor,” she says. “Virologists can be a bit conservative. But the people in veterinary sciences kept sending me dirty jokes back.”
Ticket to RIKEN. “When my Science paper came out, I bet everyone in the lab: ‘This is going to be my ticket to Japan.’ Sure enough, I was invited to give a talk at RIKEN. That was a dream come true. I always wanted to be a travel agent, because I figured it’d get me around the world. But my science has gotten me even farther.”
Bake-sale science. “I don’t like writing grants, especially when there’s no money and you’re continually writing but not getting anything. I’d rather bake brownies and cakes and sell them for $4 apiece to raise money for my lab. It would be a better use of my time, and I could make more money than I get from my grant.” A serious foodie, Skop even fantasizes about opening a bakery that would offer science-inspired treats, like the cupcakes decorated with a mitotic spindle design featured on her personal food blog, foodskop.com. Talk about a multimedia grant application!
My way is the Thai way. “My husband and I went to Thailand on our honeymoon, and I would love to retire there. The food is awesome, and the life just seemed so simple. I liked the town of Chiang Mai in the north. It reminded me of Madison—but in the jungle. There were several colleges, and it was very cosmopolitan, but on a small scale. The people were great, and it was one of the most beautiful places I’ve ever been.”
Black and white. As a graduate student, Skop went on a UNESCO-sponsored trip to South Africa. “It was the year after apartheid ended, so there was a lot of excitement in the air. The people were still trying to understand where they were in time and in history. Once, I was waiting for a bus in Cape Town and a woman came up to me and said, ‘You’re from America? You must know my cousin. He plays in a band.’ I was cracking up. Then she said, ‘You probably don’t think very highly of our country, and what’s gone on here. But our country is America—just 150 years behind.’ She was totally right. That really gave me a new perspective.”
Professor Colonel. Skop is a member of the Honorable Order of Kentucky Colonels. “It’s the highest award bestowed on a Kentuckian. The organization includes several famous scientists: Thomas Hunt Morgan and Phil Sharp. The biggest perk—maybe the only perk—is, you get first dibs on tickets for the Kentucky Derby.”
Getting the scoop on the President’s pets. As the recipient of a Presidential Early Career Award for Scientists and Engineers (PECASE) in 2006, Skop found herself a guest at the Bush White House. “Before the ceremony, we all received this big propaganda package,” she says. It included, among other things, “a photo of the White House pets, and a bunch of stickers, including one that says, ‘Barney [the First dog] says you did a good job’ It was like we were kids!” Skop affixed her Barney sticker to her lapel—a gesture that did not go unnoticed by the leader of the free world. “He walks right over to me and says, ‘Hey, that’s Barney!’ Everyone just went bonkers. I say, ‘How’s Barney?’ and he says, ‘Oh, I love my Barney.’ I also had read in the package that there was a White House cat. So I ask him, ‘How many litter boxes do you have in this place?’ He says, without hesitating, ‘Four.’ So I’m thinking, this guy is scooping the litter boxes in the White House!”
Supernanny, PhD. “When I was a postdoc in Berkeley, I baby-sat for extra cash. My friends thought I was crazy, but I’d spend a couple hours playing, put the kids to bed, and then do some work. I wrote half my Science paper while babysitting.” And it paid better than bench work, too. “I would make $20 an hour—and people would give me a $40 tip because I had a PhD.”