Protein teamwork drives successful cell division

Like a surgeon separating conjoined twins, cells have to be careful to get everything just right when they divide in two. Otherwise, the resulting daughter cells could be hobbled, particularly if they end up with too many or two few chromosomes. Successful cell division hangs on the formation of a dip called a cleavage furrow, a process that has remained mysterious. Now, researchers at Johns Hopkins have found that no single molecular architect directs the cleavage furrow’s formation; rather, it is a robust structure made of a suite of team players.

The finding is detailed in the March 2 issue of the journal Current Biology.

A cleavage furrow begins to separate a dividing cell into daughter cells. (Credit: Janet Effler/Johns Hopkins Medicine

A cleavage furrow begins to separate a dividing cell into daughter cells. (Credit: Janet Effler/Johns Hopkins Medicine

“We assumed the cleavage furrow was like a finely tuned Swiss watch, in that breaking a key component would bring it to a stop — we just didn’t know what that component was,” says Douglas Robinson, Ph.D., a professor of cell biology in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine, borrowing an analogy from the late Ray Rappaport, the founding father of modern cell division research. “But it turned out to be more like an old Maine fishing boat: almost indestructible.”

Cell division is how new cells form, both during development and throughout an organism’s life. To learn more about this process, Robinson and graduate student Vasudha Srivastava took the one-celled amoeba Dictyostelium as their model. One by one, they disabled genes for proteins known to be involved in the cleavage furrow to see whether doing so disrupted its assembly. But no matter which protein was taken out, other proteins still self-assembled to form the cleavage furrow.

“It’s not a house of cards — pulling out one protein doesn’t bring it down,” Srivastava says. Instead, she and Robinson found a robust process tuned not only by chemical signaling, but also by mechanical processes.

That makes sense, Robinson says, given the importance of the cleavage furrow to life itself. “Cells need to get division right in order to avoid ending up with the wrong number of chromosomes, which can be fatal,” he says.

The study was funded by the Hay Graduate Fellowship Fund, the National Institute for General Medical Sciences (grant number GM66817), the National Institutes of Health Office of the Director (grant number S10 OD016374) and the Johns Hopkins Physical Sciences-Oncology Center.

Douglas Robinson is an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology.

Reposted in its entirety from Johns Hopkins School of Medicine News.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, or 410-516-4802.

High school research internships keep skills fresh

For most teenagers, finding a summer job is almost a rite of passage into adulthood. It’s a chance to learn responsibility and time management and practice how to get along with coworkers. It also helps earn money for college or fun. A group of specially selected teens, however, were able to take the concept of the summer job a step further as summer research scholars in Johns Hopkins University laboratories.

High schooler Christopher Miller with his graduate student mentor Hoku West-Foyle. (Photo by Mary Spiro)

High schooler Christopher Miller with his graduate student mentor Hoku West-Foyle. (Photo by Mary Spiro)

The Summer Academic Research Experience (SARE) program, an opportunity funded in part by Johns Hopkins Institute for NanoBioTechnology and the School of Medicine, trains students from “disadvantaged” homes throughout the state. Some students may have a parent in prison or struggling with addiction. Others may face extreme financial hardship or even have been homeless.

SARE scholars have a chance to overcome obstacles to academic success by working in academia under the guidance of a mentor. They improve their writing and mathematics skills through tutoring. And they learn how to keep good laboratory records, how to follow safety protocols, and how to make a professional presentation.

“This is way better than flipping burgers,” exclaimed Stephanie Keyaka, as she prepared an image of a Western Blot performed on Drosophila eye genes. Keyaka, a tenth grader from The SEED School of Maryland, the state’s only public boarding school. She studied rhodopsin in the eyes of flies in the lab of professor Craig Montell during the summer of 2012.

SARE, launched in 2009 through a collaboration between INBT and School of Medicine cell biology associate professor Doug Robinson, recruits students from the private nonprofit Boys Hope Girls Hope of Baltimore, from The SEED School, and now also from The Crossroads School, operated by the nonprofit Living Classrooms Foundation. While the partnership with Boys Hope Girls Hope has been in place from the beginning, working with The SEED School and The Crossroads School has expanded the potential pool of qualified and interested applicants. “Expanding the applicant pool makes the program more competitive, which is a worthwhile experience—to have to compete for something,” Robinson said.

During their time at Hopkins, each SARE scholar focuses on a mini research project that advances the larger goals of the lab where they are placed. No prior laboratory work is expected, and the learning curve is steep. But with mentoring from graduate students and postdoctoral fellows, the scholars find their way. At the end of the summer, the scholars present their findings in a poster session for their peers, faculty and staff.

“At the beginning of the summer, I didn’t know what the heck I was talking about, but now I get it!” laughed Christopher Miller, a tenth grader from The SEED School. Miller studied the motor protein myosin in the Robinson lab.

Miller’s mentor, cell biology doctoral student Hoku West-Foyle, said working with students during the summer helps to re-energize the lab. “At first, it is a bit of extra work, but it gives you teaching experience, and when you are explaining your project to other people, it helps to reinforce why the larger research question matters. It fires you up to work harder,” West-Foyle said.

Shaolin Holloman, an eleventh grader at Baltimore Polytechnic Institute and Girls Hope scholar, worked in the cell biology lab of professor Carolyn Machamer. Her project sought to understand why the SARS coronavirus localizes to the Golgi apparatus of the cell.

“I liked the work experience because we actually got to do hands-on experiments,” said Hollomon, who hopes to become an orthopedic surgeon. “The biggest challenge for me was to keep up with my weekly essays, my summer reading and the work in the lab.”

Robinson hopes the program can become self-sustaining and even scalable to accept more students. “We are at a juncture where we are seeking additional funding, so we are systematically assessing our impact,” Robinson said. One would judge that the SARE program’s impact is significant, since all five alumni who have graduated from high school, or who will do so this spring, have gone on to university, Robinson reported. Two students have declared biology as their major and the other three still in high school are interested in science, technology, mathematics or health-related disciplines. Five new scholars will join SARE this summer.

Khalek Kirkland, The SEED School headmaster said summer internships of this kind are important to help keep students motivated and on track academically. “We do believe in the ‘summer brain drain,’ in that students do lose something over the summer,” Kirkland explained. “Doug and I are in talks about writing a grant together to expand the program not only to SEED School students, but to additional students as well.”

Anyone with interest in supporting the efforts of the SARE program can contact Douglas Robinson via email a

Story by Mary Spiro

More on the SARE program:

Lab coats are summer gear for high school researchers