Tag Archive for biochemistry

Joshi ’20 Honored with Research Award to Study DNA Mismatch Repair

Meera Joshi '20

Meera Joshi ’20

Meera Joshi ’20 is the recipient of an American Society for Biochemistry and Molecular Biology (ASBMB) Undergraduate Research Award for her work on the DNA mismatch repair system.

The $1,000 award will support her research titled “Exploring the Dynamics of Msh2-Msh6 Binding to Holliday Junction Through ATPase Activity. Her advisor is Ishita Mukerji, professor of molecular biology and biochemistry.

Joshi’s research focuses on a DNA mismatch repair protein called Msh2-Msh6 that initiates the repair of DNA mismatches after replication in eukaryotes. This is a highly conserved process from bacteria to humans and has implications for human health.

“We are particularly interested in Msh2-Msh6 because of it’s involvement in DNA repair, which when faulty, can lead to cancer,” Joshi explained. Mutations in this protein have been linked to Lynch syndrome, an inherited cancer syndrome, and tumor development.

Joshi is building on the work of a previous Mukerji lab student who characterized the binding affinity of Msh2-Msh6 with Holliday Junctions—a cross-shaped DNA structure with four strands of DNA, mostly seen during genetic recombination. This structure is also an important intermediate in the repair of damaged DNA. As Msh2-Msh6 usually binds to DNA containing one mismatched base pair, the lab is interested in understanding its role when binding to Holliday Junctions.

In order to study how the protein interacts with the Holliday Junction, Joshi will use fluorescent analogs to observe how the protein binds to the junction and if there are any changes in structure because of binding. The award will be used to fund the fluorescent analogs and the DNA needed for the experiments.

“Meera is a strong research student who is dedicated and hard-working,” Mukerji said. “I think she will make a lot of progress on her project this summer and am excited to see the results.”

After graduating from Wesleyan, Joshi hopes to attend graduate school and find a lab that focuses on protein dynamics.

ASBMB’s mission is to advance the science of biochemistry and molecular biology through the publication of scientific and educational journals, the organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific workforce.

Natural Sciences and Mathematics Division Hosts Celebration of Science Theses

On April 26, honors and graduate students in the Natural Sciences and Mathematics Division presented posters at the Celebration of Science Theses.

On April 26, honors and graduate students in the Natural Sciences and Mathematics Division presented posters at the Celebration of Science Theses.

Han Yang Tay presented a poster titled "Rich Club and Diverse Club in Structural and Functional Neuroimaging Data." His advisor is Psyche Loui

Han Yang Tay ’19 speaks to Barbara Juhasz, associate professor of psychology, about his study titled “Rich Club and Diverse Club in Structural and Functional Neuroimaging Data.” His advisor is Psyche Loui, assistant professor of psychology.

Case, Hingorani Coauthor Study on Repair of DNA Damaged by Sunlight

Brandon Case

Molecular biology and biochemistry graduate student Brandon Case and Professor Manju Hingorani are coauthors of a study published in Nucleic Acids Research in March 2019.

The paper, titled “The ATPase mechanism of UvrA2 reveals the distinct roles of proximal and distal ATPase sites in nucleotide excision repair,” reports new findings on how the UvrA2 protein uses its ATPase activity to probe DNA for damage lesions, such as those caused by UV radiation, and initiate nucleotide excision repair (NER). This DNA repair process corrects tens of thousands of lesions introduced daily into the human genome by UV rays and chemical agents.

2 Students Inducted into the American Society for Biochemistry and Molecular Biology Honor Society

Mackenzie Mitchell '20 and Edelina (Lina) Marzouk '19

Mackenzie Mitchell ’20 and Lina Marzouk ’19 were inducted into the ASBMB Honor Society. (Photo by Olivia Drake MALS ’08)

Two Wesleyan students were inducted into the 2019 American Society for Biochemistry and Molecular Biology (ASBMB) Honor Society in March. They are among only 33 students from around the country who were eligible to join the society this year.

The inductees, Mackenzie Mitchell ’20 and Edelina (Lina) Marzouk ’19 are both majoring in molecular biology and biochemistry and the Science in Society Program. They are both members of the ASBMB Student Chapters, have a GPA of over 3.4 on a 4.0 scale, and have demonstrated exceptional achievement in academics, undergraduate research, and science outreach.

The students were recognized by the Molecular Biology & Biochemistry Department during a reception on March 27.

Mackenzie Mitchell says the “dynamism of scientific study, as well as the complete integration of problem-solving,” have been the greatest influences over her decision to study science. Since enrolling at Wesleyan, Mitchell has furthered her interests by participating in research with Associate Professor of Molecular Biology and Biochemistry Amy MacQueen’s research group.

Case, Hingorani Coauthor Study on DNA Repair

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.

19th Annual Biophysics Retreat Includes Speakers, Poster Sessions

Wesleyan faculty, students, alumni and guests participated in the 19th annual Molecular Biophysics Retreat Sept. 27 at Wadsworth Mansion.

Wesleyan faculty, students, alumni, and guests attended the 19th annual Molecular Biophysics Retreat Sept. 27 at Wadsworth Mansion. The event included a series of speakers, two poster sessions, and a keynote address.

Alison O’Neil, assistant professor of chemistry, spoke on "Investigating the toxicity of SOD1 aggregates in a stem cell-derived model of ALS." Research in the O'Neil lab is focused on understanding the structure-function relationship of proteins involved in neurodegenerative diseases, specifically ALS.  Utilizing human stem cells allows us to study the unique cell types associated with disease. 

Alison O’Neil, assistant professor of chemistry, spoke on “Investigating the toxicity of SOD1 aggregates in a stem cell-derived model of ALS (amyotrophic lateral sclerosis).” ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Research in the O’Neil lab is focused on understanding the structure-function relationship of proteins involved in neurodegenerative diseases, specifically ALS.

Graduate Students, Faculty Attend Yeast Genetics Meeting

From the left is Anna Rogers and Lorencia Chigweshe, both graduate students in the Molecular biology and Biochemistry program.

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.

Lukens Remembered for Cofounding the Department of Molecular Biology and Biochemistry

Lewis “Lew” N. Lukens

Lew Lukens

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.

PhD Candidate Case Speaks on DNA Repair

On March 7, Brandon Case, a PhD candidate in molecular biology and biochemistry, delivered a talk titled "Just Another Day Fixing the Double Helix" as part of the Graduate Speaker Series.

On March 11, Brandon Case, a PhD candidate in molecular biology and biochemistry, delivered a talk titled “Just Another Day Fixing the Double Helix” as part of the Graduate Speaker Series. Case’s advisor is Manju Hingorani, professor of molecular biology and biochemistry, professor of integrative sciences. 

Song, Hingorani Coauthors of 2 Papers in The Journal of Biological Chemistry

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.

Olson Lab Explores How Cholera Infection Spreads

Rich Olson

Rich Olson

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.

Case, Kessler ’18 Honored for Outstanding Poster Presentations

PhD candidate Brandon Case and Emily Kessler '18 attended the North Eastern Structural Symposium at the University of Connecticut.

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.