Biological Research

Graduate students in the Division meld molecular and structural biology with physical, organic and analytical chemistry to understand the molecular basis of biological processes and human disease. Research in the Biological Division focuses on the structure, stability and function of proteins, membranes, DNA, RNA, macromolecular complexes and viruses, natural product biogenesis, synthetic biology, and genomics.

Students are a constant source of new hypotheses for mechanisms underlying cellular machines like the ribosome, spliceosome, and as well as protein and RNA folding. Students tackle these problems using biochemical methods, chemical biosensor technologies, protein and nucleic acid crystallography, in vitro and in vivo evolution, multi-dimensional NMR spectroscopy, surface chemistry, atomic-force microscopy, fluorescence spectroscopy, and high-resolution mass spectrometry.

Doctoral students in our Divsion leave the Department broadly trained for leadership roles in academia and industry.

Recent Research Results

Toxicological Responses of α-Pinene-Derived Secondary Organic Aerosol and Its Molecular Tracers in Human Lung Cell Lines

In this study, we quantified an increasing concentration response of three well-established α-pinene SOA tracers (pinic, pinonic, and 3-methyl-1,2,3-butanetricarboxylic acids) and a full mixture of α-pinene SOA in A549 (alveolar epithelial carcinoma) and BEAS-2B (bronchial epithelial normal) lung cell lines.

Protein-complex stability in cells and in vitro under crowded conditions

We review quantitative, wet-experiment based efforts aimed at understanding how and why high concentrations of small molecules, synthetic polymers, biologically relevant cosolutes and the interior of living cells affect the energetics of protein-protein interactions.

The intracellular environment affects protein–protein interactions

We quantified the stability of a model protein complex, the A34F GB1 homodimer, in buffer, Escherichia coli cells and Xenopus laevis oocytes. The complex is more stable in cells than in buffer and more stable in oocytes than E. coli.

Representative Publications

Chemical Research in Toxicology.
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Toxicological Responses of α-Pinene-Derived Secondary Organic Aerosol and Its Molecular Tracers in Human Lung Cell Lines Faria Khan, Karina Kwapiszewska, Yue Zhang, Yuzhi Chen, Andrew T. Lambe, Agata Kołodziejczyk, Nasir Jalal, Krzysztof Rudzinski, Alicia Martínez-Romero, Rebecca C. Fry, Jason D. Surratt, and Rafal Szmigielski Chemical Research in Toxicology 2021 34 (3), 817-832 DOI: 10.1021/acs.chemrestox.0c00409

Current Opinion in Structural Biology.
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Protein-complex stability in cells and in vitro under crowded conditions Samantha S. Stadmiller and Gary J. Pielak Current Opinion in Structural Biology 2021 66, 183-192 DOI: 10.1016/j.sbi.2020.10.024

Proceedings of the National Academy of Sciences .
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The intracellular environment affects protein–protein interactions Shannon L. Speer, Wenwen Zheng, Xin Jiang, I-Te Chu, Alex J. Guseman, Maili Liu, Gary J. Pielak, Conggang Li Proceedings of the National Academy of Sciences Mar 2021, 118 (11) e2019918118 DOI: 10.1073/pnas.2019918118

ACS Chemical Biology.
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Pseudomonas Virulence Factor Pathway Synthesizes Autoinducers That Regulate the Secretome of a Pathogen Ashley M. Kretsch, Gina L. Morgan, Katie A. Acken, Sarah A. Barr, and Bo Li ACS Chemical Biology 2021 16 (3), 501-509 DOI: 10.1021/acschembio.0c00901

Dried Protein Structure Revealed at the Residue Level by Liquid-Observed Vapor Exchange NMR.
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Crilly C, Brom J, Kowalewski M, Piszkiewicz S, Pielak, GJ. 2021. Dried protein structure revealed at the residue level by liquid-observed vapor exchange NMR Biochemistry 60, 152-159.

Journal of the American Chemical Society.
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Time-Resolved, Single-Molecule, Correlated Chemical Probing of RNA Jeffrey E. Ehrhardt and Kevin M. Weeks Journal of the American Chemical Society 2020 142 (44), 18735-18740 DOI: 10.1021/jacs.0c06221

In Vitro Reconstitution Reveals a Central Role for the N-Oxygenase PvfB in (Dihydro)pyrazine-N-oxide and Valdiazen Biosynthesis.
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Gina L. Morgan and Bo Li “In vitro reconstitution reveals a central role for the N-oxygenase PvfB in (dihydro)pyrazine-N-oxide and valdiazen biosynthesis,” Angew. Chem. Int. Ed., 59, 21387–21391 (2020).

More Than π–π–π Stacking: Contribution of Amide−π and CH−π Interactions to Crotonyllysine Binding by the AF9 YEATS Domain.
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Mackenzie W. Krone, Christopher R. Travis, Marcey L. Waters*, “More than π-π-π stacking: Contribution of Amide-π and CH-π interactions to crotonyl lysine binding by the AF9 YEATS domain”, https://doi.org/10.1021/jacs.0c06568