man in labradory pouring liquid into a tank
Macromolecular Structure & 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 to investigate the structure and dynamics of macromolecules include X-ray crystallography, cryo-electron microscopy, mass spectrometry, NMR 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. Our researchers explore structure and mechanism to understand how macromolecules work at both a fundamental level and in the context of molecular pathways in the cell. Such knowledge could provide the basis for new medical treatments, pollution-control strategies and many other applications.

Primary Faculty

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

Michael Cianfrocco, PhD
Structural biology and biophysics underlying microtubule-based intracellular transport

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

Tobias Giessen, PhD
Structure, function, and engineering of large protein assemblies

James Morrissey, PhD
Biochemistry of the human blood clotting system; structural studies of protein-membrane complexes

Patrick O'Brien, PhD
Biochemical, biophysical, and structural approaches to understanding mechanisms of human DNA repair

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

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

Zhaohui Xu, PhD
Structural biology and molecular mechanisms of protein folding and trafficking in eukaryotic cells

Secondary Joint Faculty

Neil Marsh, PhD
Structure and mechanism of radical S-adenosylmethionine-dependent enzymes, enzymes in hydrocarbon biosynthesis and degradation, design of self-assembling protein nano-cages

Shyamal Mosalaganti, PhD
Applying cryo-electron tomography and other biochemical and cell biological methods to understand how lysosomes perform their functions, undergo repair, and communicate with other organelles to maintain cellular fitness

Nils Walter, PhD
Powerful single molecule studies of mechanistic structure-dynamics-function relationships in RNAs of biomedical and bioanalytical significance; current work ranges from small bacterial riboswitches to RNA-protein complexes involved in human disease