Institute for Stem Education

The Center for Science and Mathematics Education (CESAME), which is housed in the Biochemistry Department, was founded by David Bynum in 2007, and has grown to become a national leader in STEM education research, teacher education, and community outreach. CESAME has been an incubator of innovative, interdisciplinary STEM education collaborations with the university and its surrounding communities. CESAME is now directed by Biochemistry and Cell Biology faculty member Keith Sheppard. CESAME has made notable contributions to STEM teaching, research, and policy at the university since 2007 including: • Generating over $ 7.5M in external grant funding. • Hiring three new tenure-track faculty members (Keith Sheppard, Angela Kelly and Ross Nehm) who collectively produce substantial amounts of high-impact discipline-based science education research; additionally, there are 10 affiliated faculty members in 8 STEM departments, 4 instructors and 3 administrative staff. • Creating a Ph.D. Program in Science Education in 2010, which currently enrolls 35 students. Doctoral courses were offered at Stony Brook Manhattan for the first time this year. • Faculty are active in state and national STEM educational policy activities, serving on editorial boards, writing policy statements, serving on advisory panels, meeting with key state leadership staff, and testifying at state-level education commissions. CESAME is a major provider of high quality STEM Teacher Education: • Offering a full complement of B.S. and M.A.T. programs in all STEM education fields and is one of the major producers of STEM teachers in the state. • Developing 24 graduate courses, of which 21 are currently active, and 7 undergraduate courses. • CESAME recently became the regional hub for the New York State Science and Mathematics Master Teacher program CESAME is a leading provider of high quality STEM outreach and student support: • CESAME has awarded $4.4M in fellowships and scholarships to post-doctoral, graduate, undergraduate, and high school students who have been actively involved in research or teaching in STEM disciplines. • Over 5,500 students attend our Teaching Labs annually; 85% of Long Island school districts have participated. Labs are offered in biology, geoscience, chemistry, sustainable chemistry and physics. Summer camps are offered in all disciplines of sciences, mathematics, and engineering. • CESAME sponsors Science Open Nights for the public and the annual Celebration of Undergraduate Research and Creative Activity. • CESAME has established research and professional development partnerships with the wider scientific community at Cold Spring Harbor Laboratories, Brookhaven National Laboratories, STEM Hub, American Museum of Natural History New York Botanical Garden, as well as NYS schools and community colleges. • CESAME annually hosts the Protein Modeling Challenge for regional high schools and also North American Computational Linguistics Olympiad.

Mechanism That Unwinds DNA May Function Like an Oil Rig “Pumpjack”

Stony Brook researchers and colleagues use high-resolution imaging of proteins to develop the theory

A team of scientists led by Stony Brook University biochemist Huilin Li, PhD, have proposed that DNA is unwound by a type of “pumpjack” mechanism, similar to the way one operates on an oil rig. Their finding, published in Nature Structural & Molecular Biology, is based on new close-up images of the proteins that unwind DNA inside the nucleus of a yeast cell and could offer insight into ways that DNA replication can go awry and trigger disease.

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Members of the research team, from front: Zuanning Yuan, Stony Brook University graduate student; Huilin Li, Professor of Biochemistry and Cell Biology; and Lin Bai and Jingchuan Sun, postdoctoral scientist and research scientist, respectively, at Brookhaven National Lab. (Photo: BNL)

“DNA replication is a major source of errors that can lead to cancer,” explained Li, a Professor in the Department of Biochemistry & Cell Biology at Stony Brook University, a scientist at Brookhaven Lab, and lead author of the paper. “The entire genome—all 46 chromosomes—gets replicated every few hours in dividing human cells,” Li said, “so studying the details of how this process works may help us understand how errors occur.”

The investigative team includes scientists from Stony Brook University, the U.S. Department of Energy’s Brookhaven National Laboratory, Rockefeller University, and the University of Texas. Their research builds on previous collaborative work led by Dr. Li. In 2015, they produced the first-ever images of the complete DNA-copying protein complex, called the replisome. That study revealed a surprise about the location of the DNA-copying enzymes—DNA polymerases.

In the new paper, titled “Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation,” the research team focused on the atomic-level details of the “helicase” portion of the protein complex—the part that encircles and splits the DNA double helix so the polymerases can synthesize two daughter strands by copying from the two separated parental strands of the “twisted ladder.”

The scientists produced high-resolution images of the helicase using a technique known as cryo-electron microscopy (cryo-EM). One advantage of this method is that the proteins can be studied in solution, which is how they exist in the cells.

“You don’t have to produce crystals that would lock the proteins in one position,” Li said, adding that this is essential because the helicase is a molecular “machine” made of 11 connected proteins that must be flexible to work. “You have to be able to see how the molecule moves to understand its function.”

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Two images showing the structure of the helicase protein complex from above. (a) A surface-rendered three-dimensional electron density map as obtained by cryo-EM. (b) A computer-generated “ribbon diagram” of the atomic model built based on the density map. The helicase has three major components: the Mcm2-7 hexamer ring in green, which encircles the DNA strand; the Cdc45 protein in magenta; and the GINS 4-protein complex in marine blue. Cdc45 and GINS recruit and tether other replisome components to the helicase, including the DNA polymerases that copy each strand of the DNA.

“The whole mechanism operates similar to an old style pumpjack oil rig, with one part of the protein complex forming a stable platform, and another part rocking back and forth,” Li explained. “Each rocking motion could nudge the DNA strands apart and move the helicase along the double helix in a linear fashion,” he suggested.

Using computer software to sort out the images revealed that the helicase has two distinct conformations—one with components stacked in a compact way, and one where part of the structure is tilted relative to a more “fixed” base.

The atomic-level view allowed the scientists to map out the locations of the individual amino acids that make up the helicase complex in each conformation. Then, combining those maps with existing biochemical knowledge, they came up with a mechanism for how the helicase works.

“One part binds and releases energy from a molecule called ATP. It converts the chemical energy into a mechanical force that changes the shape of the helicase,” Li said. After kicking out the spent ATP, the helicase complex goes back to its original shape so a new ATP molecule can come in and start the process again.

“It looks and operates similar to an old style pumpjack oil rig, with one part of the protein complex forming a stable platform, and another part rocking back and forth,” Li said. Each rocking motion could nudge the DNA strands apart and move the helicase along the double helix in a linear fashion, he suggested.

This linear translocation mechanism appears to be quite different from the way helicases are thought to operate in more primitive organisms such as bacteria, where the entire complex is believed to rotate around the DNA, Li said. But there is some biochemical evidence to support the idea of linear motion, including the fact that the helicase can still function even when the ATP hydrolysis activity of some, but not all, of the components is knocked out by mutation.

“We acknowledge that this proposal may be controversial and it is not really proven at this point, but the structure gives an indication of how this protein complex works and we are trying to make sense of it,” he said.

The study was funded by the U.S. National Institutes of Health and the Howard Hughes Medical Institute (HHMI), with additional support from the Brookhaven Lab Biology Department. High-resolution cryo-EM data were collected at HHMI and the University of Texas Health Science Center.

Notes From Chairman

2015 has been a year of changes in the Department of Biochemistry and Cell Biology.  One big change was the departure of Bob Haltiwanger, chairman of the department since 2007, who was recruited away to the University of Georgia.  The Department thrived under Bob’s leadership, including the hiring of seven new faculty members.  He is greatly missed, but we wish him well in his new surroundings. Bob’s departure necessitated another change, I have stepped in as Department chair.  I hope to see the Department continue to grow as it has under Bob.

In addition to Bob’s move, there were multiple retirements this year. Harvard Lyman, David Bynum, and Ken Marcu take with them over 100 years of experience educating and working with the students of Stony Brook.  Though all these departures are keenly felt, there have been many positive developments in the department this year as well.  The Department continued its healthy growth both in our educational mission and our research mission.  The number of students in our undergraduate courses continues to climb and this summer we will roll out our first online Biochemistry course.  Our Master’s program, begun in 2011, accepted its largest entering class ever.  On the research side, funding from research grants continues to grow and there were several exciting advances and faculty awards.

These developments are highlighted in our new and improved Newsletter.  The Newsletter is accessible through the Departmental website.  It will be updated frequently and contains a page for Alumni news.  We hope the Newsletter will not only help alumni keep in touch with the Department, but also with each other.  Please let us know what you are up to.