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Biochemistry and Molecular Biophysics

Experimental, computational and theoretical methods and techniques from chemistry have played crucial roles in the elucidation of the molecular basis of life. Challenges posed by specific biological problems are driving the development of new analytical tools and prompting advances in the physical and chemical sciences. Chemists increasingly take inspiration from and/or directly use biological processes to develop structures and materials with novel chemical functions.

Ph.D. students choose from graduate classes in Biochemistry, Molecular Cell Biology, Molecular and Cell Biophysics, Bio Imaging and Spectroscopy, Molecular Dynamics and Biomolecular Simulation, Biophysics, Molecular Quantum Chemistry, Statistical Thermodynamics, Molecular Spectroscopy.

Three proteins of the cyanobacterial circadian clock that form a self-sustained circadian oscillator when combined with ATP, courtesy of Professor Andy LiWang.Many faculty members work at the dynamic interface between chemistry and biology.

Mike Colvin's group works on modeling semi-structured biomolecular systems. Andy LiWang's group is resolving the structural and biochemical basis of rhythmicity of the circadian clock, which is used for time keeping in life cycles. Patti LiWang's group determines the structure of chemokines and how they affect HIV and inflammatory diseases.

Eva de Alba's lab studies the regulation of inflammation and cell death at the molecular level using a variety of biophysical techniques (e.g., NMR, TEM, optical tweezers/fluorescence microscopy) and designs proteins to function as biologics and for different biotechnological applications. The Noy group studies molecular transport and signal transduction across nanoscale interfaces and develops biomimetic nanostructures that facilitate the creation of bioelectronic devices and circuits.

The Sukenik lab develops live-cell microscopy methods, and combines them with spectroscopy and computational modeling to understand the complex interplay between proteins and the cellular environment in health and disease. The Ye group is engaged in the hierarchical self-assembly of nucleic acid nanostructures as well as the development of new tools to analyze single DNA molecules.

ThompsonThe Thompson Lab is creating new experimental methods that combine temperature perturbations with X-ray crystallography and other techniques, allowing them to explore the conformational landscapes of protein molecules and identify the structural states that define their biological activities.

ZoghbiThe Zoghbi group studies the structure and function of membrane transport proteins using biochemical, spectroscopic, and electron microscopy techniques.

The Subramaniam lab is developing new experimental techniques using in vitro synthetic cells to understand fundamental physicochemical mechanisms that govern the assembly and function of biomembranes and proteins.

MunozThe Muñoz group focuses on protein biophysics and engineering using a combination of experimental and computational approaches, and with the goals of understanding fundamental principles such as protein folding and the interactions between transcription factors and DNA, as well as developing applications such as the design of advanced biosensors and allosteric protein assemblies.

 

Representative Publications

Pan X, Thompson M, Zhang Y, Liu L, Fraser JS, Kelly MJS, Kortemme T., "Expanding the space of protein geometries by computational design of ​de novo fold families," Science. (2020)

E. de Alba, “Inflammasomes, Intracellular Mediators of Immune Defense,"Structure, Interactions and Self-Assembly of ASC-dependent Inflammasomes, Archives of Biochemistry and Biophysics, 670, 15-31. (2019)

D Cai, D Feliciano, P Dong, E Flores, M Gruebele, N Porat-Shilom, S Sukenik, Z Liu, J Lippincott-Schwartz, "Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression," Nature Cell Biology, 21, 578–1589. (2019)

Heisler, J., Chavan, A., Chang, Y.-G., LiWang, A., “Real-time in vitro fluorescence anisotropy of the cyanobacterial circadian clock,” Methods Protoc., 2, 42. (2019)

Yavuz B, Morgan JL, Herrera C, Harrington K, Perez-Ramirez B, LiWang PJ, Kaplan DL, "Sustained Release Silk Fibroin Discs: Antibody and Protein Delivery for HIV Prevention," Controlled Release, 301:1-12. (2019)

V. Girish, J. Pazzi, A. Li, A.B. Subramaniam, "Fabrics of diverse chemistries promote the formation of giant vesicles from phospholipids and amphiphilic block copolymers," Langmuir, 35 (28), 9264-9273. (2019)

Gu, Q., Nanney, W., Cao, H.H., Wang, H., Ye, T., "Single Molecule Profiling of Molecular Recognition at a Model Electrochemical Biosensor," American Chemical Society, 140, 14134-14143. (2018)

Shahar Sukenik, Mohammed Salam, Yuhan Wang, and Martin Gruebele, “In-Cell Titration of Small Solutes Controls Protein Stability and Aggregation,” Journal of the American Chemical Society 140 (33), 10497-10503. (2018)

Swan, J. A., Golden, S. S., LiWang, A., Partch, C. L. “Structure, function, and mechanism of the core circadian clock in cyanobacteria,” J. Biol. Chem., 293, 5026-5034. (2018)

Welkie, D. G., Rubin, B. E., Chang, Y. -G., Diamond, S., Rifkin, S. A., LiWang, A., Golden, S. S. “Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA,” Proc. Natl. Acad. Sci. USA, 115, E7174-E7183. (2018)

CM Davis, M Gruebele, S Sukenik, "How does solvation in the cell affect protein folding and binding?" Current opinion in structural biology, 48, 323-29. (2018)

Yuhan Wang, Shahar Sukenik, Caitlin M. Davis, and Martin Gruebele, “Cell Volume Controls Protein Stability and Compactness of the Unfolded State,” The Journal of Physical Chemistry B 122 (49), 11762-11770. (2018)

Zoghbi ME, Mok L, Swartz DJ, Singh A, Fendley GA, Urbatsch IL, Altenberg GA, "Substrate-induced conformational changes in the nucleotide-binding domains of lipid bilayer-associated P-glycoprotein during ATP hydrolysis," J Biol Chem, 292(50):20412-20424. doi: 10.1074/jbc.M117.814186. Epub 2017 Oct 9. PMID: 29018094 (2017)

Zoghbi ME, Mok L, Swartz DJ, Singh A, Fendley GA, Urbatsch IL, Altenberg GA, "Substrate-induced conformational changes in the nucleotide-binding domains of lipid bilayer-associated P-glycoprotein during ATP hydrolysis," Journal of Biological Chemistry Dec 15;292(50):20412-20424. doi: 10.1074/jbc.M117.814186. Epub 2017 Oct 9. PMID: 29018094. (2017)

S Sukenik, P Ren, M Gruebele, "Weak protein-protein interactions in live cells are quantified by cell-volume modulation," PNAS, 114, 6776-6781. (2017)

Tseng, R., Goularte, N. F., Chavan, A., Luu, J., Cohen, S. E., Chang, Y.-G., Heisler, J., Li, S., Michael, A. K., Tripathi, S., Golden, S. S., LiWang, A., Partch, C. L., "Structural basis of the day-night transition in a bacterial circadian clock," Science, 355, 1174-1180. (2017)

Li Zhang, Carolina Herrera, Jeannine Coburn, Natalia Olejniczak, Paul Ziprin, David Kaplan, and Patricia J. LiWang, "Sustained release and stability to high temperatures of HIV inhibitors by encapsulation in silk fibroin disks," ACS:Biomaterials, 3, 1654-1665. (2017)