Tag Archive for biochemistry

McAlear Lab Makes Fundamental Discovery About How Cells Control Genes

Jeff Arace '12, pictured in the foreground, and Ph.D candidate James Arnone, pictured in the back, work on transcriptional regulation of paired genes involved in ribosome biogenesis with their advisor, Michael McAlear, chair and associate professor of molecular biology and biochemistry, in center. Adam Robbins-Pianka BA ’08, MA ’10 and Sara Kass-Gergi ’12 also work in the McAlear Lab.

Jeff Arace ’12, pictured in the foreground, and Ph.D candidate James Arnone, pictured in the back, work on ribosome biogenesis reserarch with their advisor, Michael McAlear, chair and associate professor of molecular biology and biochemistry, in center. Adam Robbins-Pianka BA ’08, MA ’10 and Sara Kass-Gergi ’12 also work in the McAlear Lab.

(Story contributed by Jim H. Smith)

A recent discovery made by Michael McAlear, chair and associate professor of molecular biology and biochemistry, and four of his students helps explain the function of ribosomes and sheds light on genetic processes scientists have been trying to decode for more than half a century. A paper authored by McAlear and his laboratory team, describing the discovery, was published last month in the distinguished journal BMC Genomics.

The discovery resulted from long-term research into the regulation of ribosomes, often described as molecular “machines,” the organelles of all living cells in which protein synthesis occurs. Guided by genetic “blueprints” delivered to them by messenger RNA, ribosomes gather amino acids, the building blocks of protein, and assemble them into polypeptides, the intricate chains of amino acids that, depending upon their arrangement, form the unique protein characteristics required for specific biological functions.

Scientists have known about ribosomes and their essential function for a long time. Cell biologist George Palade was awarded the 1974 Nobel Prize in Physiology and Medicine for discovering them in 1955.  But while scientists have understood what ribosomes are and what they do, they’ve spent the last half century trying to decipher the complex array of metabolic processes that play a role in the production of new proteins. It is one thing to know what ribosomes do, quite another to know how they do it.

Holmes Receives NIH Grant for Histone Protein Research

Scott Holmes, associate professor of molecular biology and biochemistry, received a grant worth $374,150 from the National Institutes of Health. The grant will support a study on “Functional interaction of histone H1 with the core nucleosome” until 2015. Several Wesleyan undergraduates conducted experiments crucial for developing this grant proposal, including Samantha Schilit ’10, MA ’11, who is currently in her first year as a Ph.D. candidate at the Harvard School of Medicine.

Histone proteins organize DNA into its basic organizational unit, the chromosome, and have a fundamental influence on the function of DNA. The four core histones assemble into the disc-shaped nucleosome, while the fifth histone, H1, associates with the DNA linking adjacent nucleosomes. While histone H1 is essential for life in most organisms, its specific functions remain enigmatic.

“We are using molecular genetics to examine the function of histone H1 in yeast cells, focusing on the joint contributions histone H1 and the core histones make to regulating gene expression,” Holmes explains.

Student Research Presented at Molecular Biophysics Retreat

Wesleyan hosted the 13th Annual Molecular Biophysics and Biological Chemistry Retreat Sept. 27 at Wadsworth Mansion in Middletown. Bertrand Garcia-Moreno, professor and chair of the Department of Physics at Johns Hopkins University delivered the keynote address on “Molecular Determinants of Electrostatic Effects in Proteins." García-Moreno investigates the relationships between protein structure, function, energetics, and dynamics with an emphasis on electrostatic properties that govern the actions of proteins in all biological processes.

Wesleyan hosted the 13th Annual Molecular Biophysics and Biological Chemistry Retreat Sept. 27 at Wadsworth Mansion in Middletown. Bertrand Garcia-Moreno, professor and chair of the Department of Physics at Johns Hopkins University delivered the keynote address on “Molecular Determinants of Electrostatic Effects in Proteins.” García-Moreno investigates the relationships between protein structure, function, energetics, and dynamics with an emphasis on electrostatic properties that govern the actions of proteins in all biological processes.

Graduate student Claire Fournier presented her research on “Identification of translation initiation at downstream start codons: strategies for testing MS/MS search algorithms.” Fournier’s advisors are Michael Weir, director of Hughes Program in the Life Sciences, professor of biology; and Danny Krizanc, associate professor of environmental studies, professor of computer science.

Graduate student Claire Fournier presented her research on “Identification of translation initiation at downstream start codons: strategies for testing MS/MS search algorithms.” Fournier’s advisors are Michael Weir, director of Hughes Program in the Life Sciences, professor of biology; and Danny Krizanc, associate professor of environmental studies, professor of computer science.

McAlear Lab Publishes Paper on Co-Regulated Gene Pairs

Michael McAlear, chair and associate professor of molecular biology and biochemistry, is the co-author of “The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes,” published in BMC Genomics, October 2012. The article is online here.

The co-authors are Ph.D candidate James Arnone and Jeffrey Arace ’12; Adam Robbins-Pianka BA ’08, MA ’10; and  Sara Kass-Gergi ’12.

The team investigated co-regulated gene sets in S. cerevisiae beyond those related to ribosome biogenesis, and found that a number of these regulons, including those involved in DNA metabolism, heat shock, and the response to cellular stressors were also significantly enriched for adjacent gene pairs. While it has long been understood that there are connections between genomic organization and transcriptional regulation, this study reveals that the strategy of organizing genes from related, co-regulated pathways into pairs of immediately adjacent genes is widespread, evolutionarily conserved, and functionally significant.

MacQueen Lab’s Research Published in PLOS Genetics

Amy MacQueen, assistant professor of molecular biology and biochemistry; Karen Voelkel Meiman, research associate; and Sarah Moustafa BA’11, MA’12 are co-authors of the paper, “Full-Length Synaptonemal Complex Grows Continuously during Meiotic Prophase in Budding Yeast,” published by PLOS Genetics, Oct. 11, 2012. Moustafa worked on the paper as an undergraduate researcher and again as a BA/MA student. An abstract and the  paper is online here.

MB&B Department Attends Yeast Genetics Meeting at Princeton

Faculty and students from the Molecular Biology and Biochemistry Department gather at the 2012 Yeast Genetics & Molecular Biology Meeting in August.

Faculty, graduate students and recent alumni from the Molecular Biology and Biochemistry Department gather at the 2012 Yeast Genetics & Molecular Biology Meeting in August.

The Molecular Biology and Biochemistry Department sent three professors and six students to the international 2012 Yeast Genetics & Molecular Biology Meeting held at Princeton University recently, giving Wesleyan the largest per capita representation in the world.

Attending from the department were Associate Professor and Chair Michael McAlear and his graduate student, James Arnone; Assistant Professor Amy MacQueen and her graduate students Pritam Mukherjee and Lina Yisehak, and recent alumni Sarah Beatie ’12 and Louis Taylor ’12; and Associate Professor Scott Holmes and his graduate student, Rebecca Ryznar. All spoke or presented on various aspects of yeast genetics, molecular biology, mitosis and gene expression.

The meeting, sponsored by the Genetics Society of America and held July 31-Aug. 5, is the premier meeting for students, postdoctoral fellows, research staff, and principal investigators studying various aspects of eukaryotic biology in yeast.

NIH Supports Olson’s Infectious Disease Therapy Research

Rich Olson

Rich Olson

Rich Olson, assistant professor of molecular biology and biochemistry, received a grant worth $460,197 from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases on Aug. 8. The grant will support his research on “Mechanism of Cell Membrane Targeting by Vibrio cholera Cytolysin” through July 31, 2015.

Vibrio cholerae cytolysin (VCC) belongs to a family of secreted toxins produced by pathogenic bacteria that allows them to evade the immune system and to colonize the human body. Understanding how bacteria and their toxins target cells is important in developing therapies against human infectious diseases.

Students Accepted into Molecular Biology Honor Society

Three Wesleyan students were accepted into the American Society for Biochemistry and Molecular Biology Honor Society.
The students are Lee Gottesdiener ’12, Sophia Levan ’12 and Alejandra Olvera ’12.

These outstanding students have been selected based on their academic achievements, their commitment to research and science outreach.

The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization with more than 12,000 members. Founded in 1906, the Society is based in Rockville, M.D. The Society’s purpose is to advance the science of biochemistry and molecular biology through publication of scientific and educational journals: the Journal of Biological ChemistryMolecular & Cellular Proteomics,  and the Journal of Lipid Research, 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.

Hingorani Group Publishes 8 Papers on DNA Mismatch Repair

A research group led by Manju Hingorani, associate professor of molecular biology and biochemistry, has published eight papers in 2011-2012 on the mechanisms of DNA replication and repair proteins, independently and in collaboration with research groups at Wesleyan and other national and international universities.

The papers are:

“Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signaling,” published in The EMBO Journal, 2012 (in press).

The Variable Sub-domain of Escherichia coli SecA functions to regulate in the SecA ATPase Activity and ADP release,” published in the Journal of Bacteriology, 2012 (March 2 Epub). Don Oliver, the Daniel Ayres Professor of Biology, professor of molecular biology and biochemistry, was the lead investigator and Fred Cohan, professor of biology, professor of environmental studies, was a co-author on this paper.

Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA,” published in Nucleic Acids Research, 2012 (Feb, 24 Epub).

Biochemical analysis of the human mismatch repair proteins hMutSαMSH2G674A-MSH6 and MSH2-MSH6T1219D,” published in the Journal of Biological Chemistry, 2012 (Jan. 25 Epub).

ATP Binding and Hydrolysis-Driven Rate-Determining Events in the RFC-Catalyzed PCNA Clamp Loading Reaction,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 176-91.

A Central Swivel Point in the RFC Clamp Loader Controls PCNA Opening and Loading on DNA,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 163-75.

Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6,” published in the Journal of Biological Chemistry, Nov. 18, 2011; 286(46), pages 40287-95.

Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS,” published in the Biophysical Journal, Oct. 5, 2011;101(7), pages 1730-9. David Beveridge, the Joshua Boger Professor of the Sciences and Mathematics, was the lead investigator on this paper.

“Drug Design” Topic of Sept. 22 Biophysics and Biological Chemistry Retreat

Christina Othon, assistant professor of physics, will speak on "Phase Transitions in Biological Membranes" during the Molecular Biophysics and Biological Chemistry Retreat.

“Drug Design from Transition State Analysis” will be the central topic of the 12th annual Molecular Biophysics and Biological Chemistry Retreat Sept. 22. The public is invited to the retreat, which will be held at Wadsworth Mansion in Middletown.

Faculty from chemistry, physics and biology will present lectures.

Mukerji’s Study on Protein Binding Published in Biochemistry

Ishita Mukerji, professor of molecular biology and biochemistry, director of graduate studies, is the co-author of ““HU Binding to a DNA Four-Way Junction Probed by Förster Resonance Energy Transfer,” published in Biochemistry, issue 50, pages 1432–1441, 2011. This work specifically examines the Escherichia coli protein HU’s four-way junction interaction using fluorescence spectroscopic methods.

This work was supported by grants from the National Science Foundation and the Patrick and Catherine Weldon Donaghue Medical Research Foundation.

Toxin Study by Olson, De Published in PNAS

In a newly published paper, Rich Olson, assistant professor of molecular biology and biochemistry, describes studies of a toxin produced by the bacterium that causes cholera.

The paper –“Crystal structure of the Vibrio cholerae cytolysin heptamer reveals common features among disparate pore-forming toxins” – is the culmination of nearly eight years work. Co-authored with Swastik De, a graduate student in Olson’s lab, the paper has been published online by Proceedings of the National Academy of Sciences (PNAS) and will appear in a print edition later this spring.

Olson’s lab studies the molecular details of how pathogens invade human hosts.  Bacteria produce toxins to protect themselves from hosts’ immune systems and to scavenge materials necessary for colonization. Understanding how toxins affect host cells could lead to better treatments in some cases.