Macromolecular Structure and Mechanism

Many investigators in the department focus on how biological macromolecules function at the molecular and atomic level through a combination of modern biochemistry and structural biology. Techniques that are being employed to investigate structure and dynamics of macromolecules include X-ray crystallography, cryo-electron microscopy, NMR, mass spectrometry, and single-molecule studies, while their chemical behavior is being characterized by rapid-reaction and steady-state kinetics, calorimetry, chemical analyses, and a variety of spectroscopies. Proteins and nucleic acids are also being engineered to study how macromolecular structure determines function. These experimental approaches enable investigators to probe mechanism and specificity in order to gain a greater understanding of how macromolecules work and how they function in the context of molecular pathways in the cell. Such knowledge could provide the basis for new medical treatments, pollution-control strategies, or many other applications.

The molecular mechanism of recruitment of CENP-A, a centromere-specific histone H3 variant, to the centromere is one of the research interests of the Cho lab.
The Cianfrocco lab focuses on the structural biology and biophysics underlying microtubule-based intracellular transport.
Modified phospholipids are tools used by the Morrissey lab to analyze structures of protein-membrane complexes at the atomic level.
Structures and mechanisms of enzymes involved in human base excision repair are under investigation in the O'Brien lab.
The Weidmann lab uses in-cell chemical probing to learn about RNA structure and ribonucleoprotein (RNP) networks that govern cellular function and dysfunction.

Primary Faculty

Ruma Banerjee, Ph.D.

Chemical biology of hydrogen sulfide signaling; regulation of mammalian sulfur metabolism in health and disease; structural enzymology of human B12 trafficking proteins

Jay Brito Querido, Ph.D.

Single-particle cryo-electron microscopy in combination with biochemical approaches to study how messenger RNA translation is regulated in human health and disease

Uhn-Soo Cho, Ph.D.

Biochemical and structural studies of kinetochore assembly, histone chaperones, and Sestrin-mediated mTORC1 regulation

Michael Cianfrocco, Ph.D.

Structural biology and biophysics underlying microtubule-based intracellular transport

Lydia Freddolino, Ph.D.

High throughput structure-based function prediction, optimal use of cross-linking mass spectrometry for structure determination, structural genomics

Tobias Giessen, Ph.D.

Structure, function, and engineering of large protein assemblies

James Morrissey, Ph.D.

Biochemistry of the human blood clotting system; structural studies of protein-membrane complexes

Patrick O'Brien, Ph.D.

Biochemical, biophysical, and structural approaches to understanding mechanisms of human DNA repair

Bruce Palfey, Ph.D.

Enzyme reaction mechanisms and inhibitor design, with a focus on therapeutically important flavoproteins

Stephen Ragsdale, Ph.D.

Molecular mechanisms of enzymes involved in metabolism of energy-relevant and greenhouse gases (CO, CO₂, methane), heme, and methylmercury; mechanisms of nickel, B12, heme, and iron-sulfur enzymes

Janet Smith, Ph.D.

Structure-function studies of proteins using X-ray crystallography, with an emphasis on complex enzymes and the replication proteins of flaviviruses and alphaviruses

Raymond Trievel, Ph.D.

Chemical and structural biology of enzymes that covalently modify histones, transcription factors, and other nuclear proteins; current research focuses on elucidating the molecular mechanisms underlying the specificities of histone methyltransferases and demethylases and on developing new assays and reagents to characterize them

Chase Weidmann, Ph.D.

In-cell chemical probing to learn about RNA structure and ribonucleoprotein (RNP) networks that govern cellular function and dysfunction

Zhaohui Xu, Ph.D.

Structural biology and molecular mechanisms of protein folding and trafficking in eukaryotic cells