Molecular biology and biochemistry graduate student Brandon Case and Manju Hingorani, professor of molecular biology and biochemistry, are coauthors on a study published in Nucleic Acids Research in October 2018.
The paper, titled “Coordinated protein and DNA conformational changes govern mismatch repair initiation by MutS,” reports new findings on how the Mutator S (MutS) protein repairs mistakes in the DNA sequence, which is essential for maintaining the accuracy of the genetic code.
The collaborative effort from researchers at Wesleyan, the University of North Carolina at Chapel Hill, and North Carolina State University employed single molecule and ensemble kinetic methods to study the mechanism of action of MutS. The outcome is a unified model of coordinated changes in MutS and DNA conformation that enable the protein to recognize errors in DNA and initiate their repair.
The research at Wesleyan was supported by NIH grant R15 GM114743 awarded to Manju Hingorani.
Graduate students Anna Rogers and Lorencia Chigweshe presented their poster at the GSA meeting.
Two Wesleyan graduate students and two faculty members presented posters at the GSA Yeast Genetics and Molecular Biology Meeting held at Stanford University on Aug. 22–26. This meeting, which is held once every two years, is organized by the Genetics Society of America (GSA). The meeting brings together hundreds of scientists making groundbreaking discoveries in the field of genetics and gene regulation using the innovative power of yeast genetics.
Both students received a travel grant through Wesleyan’s Melnick Fund to support travel to the conference.
Lorencia Chigweshe presented a poster titled “Interactions between histone variant H2A.Z and linker histone H1 in Saccharomyces cerevisiae meiosis,” while Anna Rogers presented “The histone variant H2A.Z promotes chromosome condensation in Saccharomyces cerevisiae.” Both students are mentored by Scott Holmes, professor of molecular biology and biochemistry, whose lab investigates how the processes of chromosome segregation and gene expression are regulated in eukaryotes.
“We had the opportunity to engage with experts in the field of yeast genetics and learn from them and get insight on our own work,” Chigweshe said. “The conference was a great opportunity to appreciate yeast as a powerful tool for understanding genetics in addition to its industrial application in beer and bread-making.”
Amy MacQueen, associate professor of molecular biology and biochemistry, associate editor for Genetics, cochaired a workshop on scientific publishing and also presented a poster titled “Synapsis and recombination unite at the Zip1’s N-terminal tip” while Mike McAlear, associate professor of molecular biology and biochemistry, presented “Adjacent gene co-regulation (AGC) as a strategy for transcriptional control and coupling.” McAlear is also associate professor, integrative sciences, and Holmes is also professor, integrative sciences.
Lewis “Lew” Lukens, professor emeritus of molecular biology and biochemistry, passed away on Sept. 8 at the age of 91.
Lukens received his BA from Harvard University and his PhD from the University of Pennsylvania. He came to Wesleyan in 1966, first in the Biology Department and then as one of the founding members of the Department of Molecular Biology and Biochemistry, where he remained until his retirement in 1999.
Lukens’ research involved the regulation of gene expression by eukaryotic cells, specifically the genes for Type I and Type II collagen. He received many research grants from the National Institutes of Health, National Science Foundation, and the United States Department of Agriculture. During his years at Wesleyan, Lew served as chair of the Biology Department, on the Committee on Graduate Instruction, and as program director of the Biomedical Research Support Grant. In his retirement, he served on the advisory board of the Wasch Center for Retired Faculty.
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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.
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.
PhD candidate Brandon Case and Emily Kessler ’18 attended the North Eastern Structural Symposium at the University of Connecticut.
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.
Wesleyan’s Molecular Biophysics Program hosted its 18th annual retreat Sept. 28 at Wadsworth Mansion in Middletown. Wesleyan affiliated speakers included:
Professor Francis Starr spoke about DNA junction dynamics and thermodynamics during the 18th annual Molecular Biophysics Retreat.
- 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)
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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.
In this illustration, the hairpin is highlighted in cyan. The hairpin is formed by the initiator part of a protein.
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).
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Ben Oppenheim ’02, a senior fellow at the Center on International Cooperation, as well as a consulting scientist with the start-up Metabiota, writes about the importance of international collective action for pandemic preparedness.
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,
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