Tag Archive for biochemistry
by Olivia Drake •
Molecular Biology and Biochemistry Professor Manju Hingorani and graduate student Bo Song are coauthors of two studies published in The Journal of Biological Chemistry and Nucleic Acids Research in February 2018.
The papers are titled “Positioning the 5′-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage” and “Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.”
The research is related to Song’s PhD dissertation, which he plans to defend in April 2018. Song examined the mechanism of action of human FEN1, an enzyme that cleaves extra single-stranded segments of DNA before they can damage the genome, and thus serves as a guardian of genome stability. Song’s major findings were published in JBC, and he contributed to a study led by Dr. Samir Hamdan’s laboratory at King Abdullah University of Science and Technology in Saudi Arabia, which was published in NAR.
“Bo initiated research on FEN1 in my laboratory, and his interest in FEN1 sparked an exciting collaboration with Dr. Hamdan, halfway around the world. We look forward to furthering investigation of this critical enzyme whose malfunction is associated with many human cancers,” Hingorani said.
The research at Wesleyan University was supported by NIH grant R15 GM114743 awarded to Manju Hingorani.
by Himeka Curiel •
Associate Professor of Molecular Biology and Biochemistry Rich Olson and members of his lab have uncovered the structural basis for how the bacterial pathogen responsible for cholera targets carbohydrate receptors on host cells—an important finding for the future development of treatment strategies against infectious bacteria.
In their paper “Structural basis of mammalian glycan targeting by Vibrio cholerae cytolysin and biofilm proteins,” published in the Feb. 12 issue of PLoS Pathogens, Olson and his team—Swastik De PhD ’16; graduate students Katherine Kaus and Brandon Case; and Shada Sinclair ’16—looked at Vibrio cholerae, an aquatic microbe responsible for cholera, a potentially life-threatening disease for populations with limited access to health care.
The team studied two of the virulence factors that this particular bacterial pathogen uses to help spread infection: a toxin that creates pores in the membranes of target cells (such as immune cells) and a protein that helps form a protective sheath around the bacterial colonies as they grow.
Study results showed that both of these factors use similar carbohydrate receptors to recognize and target cell surfaces, suggesting that strategically disrupting carbohydrate interactions could affect how V. cholerae and other organisms like it are able to infect human hosts and spread disease.
“Understanding how pathogens specifically recognize targets on human cells is essential for the development of effective drugs and vaccines to fight pathogenic bacteria and prevent outbreaks,” Olson explained.
Read the full paper here.
by Olivia Drake •
Molecular Biology and Biochemistry PhD candidate Brandon Case and Emily Kessler ’18 recently won poster awards at the North Eastern Structural Symposium (NESS) at the University of Connecticut on Oct. 28.
Both students research the mechanisms of action of DNA replication and repair proteins with Manju Hingorani, chair and professor of molecular biology and biochemistry, professor of integrative sciences. Hingorani’s DNA Lab investigates proteins responsible for DNA replication and repair. These proteins maintain genome and cell integrity, and their malfunction leads to cancer and other diseases.
Case received an Outstanding Poster Award for his work, “Coordinated Actions of Four ATPase Sites on UvrA2 During Initiation of Nucleotide Excision Repair.”
Kessler, who is a Wesleyan Beckman Scholar, received an Outstanding Undergraduate Poster Award for “Investigating the MutS Conformational Dynamics During MMR Initiation of Lynch Syndrome-Linked MutS Mutants.” The NESS created this undergraduate award only for Kessler after hearing her presentation.
by Olivia Drake •
Wesleyan’s Molecular Biophysics Program hosted its 18th annual retreat Sept. 28 at Wadsworth Mansion in Middletown. Wesleyan affiliated speakers included:
- Colin Smith, assistant professor of chemistry, on “An Atomistic View of Protein Dynamics and Allostery;”
- Meng-Ju Renee Sher, assistant professor of physics, on “Tracking Electron Motions Using Terahertz Spectroscopy;”
- Kelly Knee, PhD ’07, principle scientist for Pfizer’s Rare Disease Research Unit, on “Protein Folding Chaperones: Molecular Machines for Tricky Problems;”
- and Francis Starr, professor of physics, director of the College of Integrative Sciences, on “DNA Four-Way Junction Dynamics and Thermodynamics: Lessons from Combining Simulations and Experiments.”
Arthur Palmer, the Robert Wood Johnson, Jr. Professor of Biochemistry and Molecular Biophysics at Columbia University Medical Center, delivered the keynote address on “Conformational dynamics in molecular recognition and catalysis: Lessons from ribonuclease H, AlkB, and GCN4.”
The day-long retreat also included two poster sessions, where undergraduates, graduate students and faculty shared their research with their peers and colleagues. The event concluded with a reception.
The Molecular Biophysics Training Program, Chemistry Department, and Molecular Biology and Biochemistry Department sponsored the event.
Photos of the retreat are below: (Photos by Olivia Drake)
by Olivia Drake •
Three scholars from the Molecular Biology and Biochemistry Department are co-authors of a study published in The Journal of Biological Chemistry in August 2017. The paper is titled “Linchpin DNA-binding residues serve as go/no-go controls in the replication factor C-catalyzed clamp loading mechanism.”
The co-authors, Manju Hingorani, chair and professor of molecular biology and biochemistry, professor of integrative sciences; Juan Liu, research associate; and Zayan Zhou, PhD ’13, performed the study on Replication Factor C (RFC) and proliferating cell nuclear antigen (PCNA), which are two essential proteins required for DNA replication and repair in all living organisms.
The researchers found new mechanistic information about how different parts of the RFC protein work together to load PCNA onto DNA (by “clamp loading”), which allows PCNA to help dozens of other proteins to replicate and repair DNA.
The Hingorani group investigates proteins responsible for DNA replication and repair. These proteins maintain genome and cell integrity, and their malfunction leads to cancer and other diseases.
by Olivia Drake •
All cells — bacterial or human — secrete up to 10 or 20 percent of the proteins that they make. Human secreted proteins, for example, include components of serum, hormones, growth factors that promote cell development during embryogenesis and tissue remodeling, and proteins that provide the basis for immune cell signaling during infection or when fighting cancer.
The secretion process, however, isn’t an easy feat for cells, as they need to move the proteins across a membrane through a channel. Transport requires the formation of a hairpin, formed by an initiator protein.
In a recent study, Don Oliver, the Daniel Ayres Professor of Biology, professor of molecular biology and biochemistry, and Ishita Mukerji, the Fisk Professor of Natural Science, professor of molecular biology and biochemistry, explain the importance of where and why hairpins form and how they help proteins move across the cell.
The study, titled “Alignment of the protein substrate hairpin along the SecA two-helix finger primes protein transport in Escherichia coli,” brings together key areas of membrane biochemistry, structural biology and molecular biophysics, and has innovative applications of molecular genetics and fluorescence spectroscopy. It was published in the Aug. 7 issue of Proceedings of the National Academy of Sciences (PNAS).
by Cynthia Rockwell •
Ben Oppenheim ’02, a consulting scientist with Metabiota, a start-up focusing on epidemiological modeling and epidemic risk preparedness, was recently invited to participate in a workshop at the National Academy of Medicine. As a result, Oppenheim and his colleagues wrote an article published in Lancet Global Health titled “Financing of International Collective Action for Epidemic and Pandemic Preparedness,” based on these meetings. Also writing for the Brookings Institution, Oppenheim further explored the challenges of responding to global outbreaks, offering a four-point plan to protect the global poor during pandemics, with co-author Gavin Yamey.
“Post-Ebola and Zika, there’s been increasing worry—and debate—about how to prepare for epidemics and pandemics that threaten global health,” notes Oppenheim, who is also a senior fellow and visiting scholar at New York University’s Center on International Cooperation. “Cracking the problem means thinking through the ways that policy, economics, health, and other factors all intertwine. In the workshop, we were thinking about how to build incentives to improve disease surveillance and outbreak detection, as well as how to improve the legal and economic architecture to speed up the development of vaccines and therapeutics. All of this demands attention to everything from epidemiology, to financing, and to politics.”
Oppenheim also discussed the economic impacts of pandemics,
by Cynthia Rockwell •
In March, during Wesleyan’s spring break, Associate Professor of Molecular Biology and Biochemistry Michael McAlear took a trip to visit and catch up with three alumni whom he’d known when they were undergraduates, just beginning the nonprofits for which they are now known. McAlear doesn’t see them often: they live and work in Africa. All three had received Wesleyan’s Christopher Brodigan Award in their senior year, for research or work in Africa.
McAlear’s first stop was in Kibera, the largest slum in Kenya, and home of SHOFCO, Shining Hope for Community, the nonprofit begun by Jessica ’09 and Kennedy ’12 Odede. Linking education for girls with community services, the organization has grown since McAlear had last visited in 2010 to help set up the school, when it held only two classes of girls ages 6 and 7, and the group was building a clinic was built to honor Johanna Justin-Jinich ’10, the student slain in the spring of 2009. At that time, McAlear offered the young students a lecture on clean water and also became a sponsor for one little girl, a responsibility and relationship that is ongoing,
“I was overwhelmed by the need in Kibera— and the optimism and fearlessness of Kennedy and Jessica; you couldn’t help being swept up by that,” McAlear recalls. “They were so young and naïve that they didn’t know what they couldn’t do—so they just kept on doing things.”
Students Inducted into Honor Society, Win Awards At American Society for Biochemistry and Molecular Biology
by Lauren Rubenstein •
Five Wesleyan seniors were inducted into the American Society for Biochemistry and Molecular Biology honor society at the ASBMB annual meeting in Chicago, April 22-26. They are: Jennifer Cascino ’17, Kaileen Fei ’17, Julianne Riggs ’17, Rachel Savage ’17 and Stacy Uchendu ’17.
The ASBMB Honor Society recognizes exceptional undergraduate juniors and seniors who are pursuing a degree in the molecular life sciences for their scholarly achievement, research accomplishments, and outreach activities. The mission of the society is to advance the science of biochemistry and molecular biology through organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, promotion of the diversity of individuals entering the scientific workforce, and publication of a number of scientific and educational journals, including the Journal of Biological Chemistry and the Journal of Lipid Research.
Bios of all the inductees, in alphabetical order, can be found here.
Riggs attended the meeting, where she took part in the induction ceremony and presented her research.
“Overall, it was a great experience. I got to present in the undergraduate poster competition and won honorable mention for best chromatin and gene expression poster. I also presented my poster to the general meeting,” she said. “It was a huge conference and there was so much going on. It was great to talk to people of all levels of science, get their perspectives on what it takes to be a scientist, and hear them passionately discuss their research projects. It was also wonderful to talk to people who were researching similar topics to mine, and get their advice and validation on my work.”
In addition, two students, Christine Little ’18 and Cody Hecht ’18, received ASBMB research awards. The $1,000 awards will support their research over the summer.
by Andrew Logan ’18 •
Wesleyan co-authors published a paper titled “The Stories Tryptophans Tell: Exploring Protein Dynamics of Heptosyltransferase I from Escherichia coli” in the January 2017 issue of Biochemistry.
The co-authors include chemistry graduate student Joy Cote; alumni Zarek Siegel ’16 and Daniel Czyzyk, PhD ’15; and faculty Erika Taylor, associate professor of chemistry; Ishita Mukerji, the Fisk Professor of Natural Science, professor of molecular biology and biochemistry.
Their paper investigates the intrinsic properties of Tryptophan amino acids found within the protein, Heptosyltransferase I, to understand the ways this protein moves during catalysis. Understanding the movement of this protein is an important step in developing its inhibitors.
When this protein is inactive, either because it was genetically altered or inhibited, hydrophobic antibiotics become more effective, so inhibitors could be useful in reactivating antibiotics that are current not effective against these bacteria.
While it is popularly believed that inhibiting a protein requires a compound to compete with the substrate, their paper argues that instead one can design a inhibitor to disrupt protein dynamics, preventing activity. The co-authors compare the function of this “protein dynamics disruptor” to a wedge holding open a door–once inserted, the inhibitor prevents the protein from performing its function.
Their research on Tryptophan residues also found that distant regions of the protein communicate whether or not they are binding their substrate to other regions.
“It would be like if your right hand knew that your left hand was holding a pencil just by the changes in the position of your left hand. We are currently pursuing computational studies to look for these motions via molecular dynamics experiments,” Taylor said.
by Frederic Wills '19 •
Three Wesleyan Molecular Biology and Biochemistry majors received the unique opportunity of presenting their thesis work at the 61st annual Biophysical Society meeting in New Orleans, Feb. 11-15.