Areas of Interest
The regulatory networks of bacteria play a key role in their information processing capabilities, coordinating and executing interactions with their environments. Quantitative, predictive models of these networks would be tremendously beneficial for facilitating the development of new antimicrobial therapies, enabling synthetic biology applications, and understanding bacterial evolution and ecology. Ultimately, the aim of my laboratory is to build a multiscale framework enabling modeling of bacterial regulatory networks at any level of detail, from atomistic to cellular. To this end, we develop and apply high-throughput experimental methods for measuring biomolecular interactions and cellular regulatory states in vivo, and for profiling the phenotypic consequences of regulatory changes. In tandem with these experimental approaches, we use molecular simulation and mathematical modeling to obtain high-resolution insight into the biomolecular interactions driving regulatory networks, and the systems-level effects of altering them.
RNase H genes cause distinct impacts on RNA:DNA hybrid formation and mutagenesis genome wide.
Schroeder JW, Hurto RL, Randall JR, Wozniak KJ, Timko TA, Nye TM, Wang JD, Freddolino PL, Simmons LA.
Sci Adv. 2023; 9: eadi5945.
Escherichia coli Leucine-Responsive Regulatory Protein Bridges DNA In Vivo and Tunably Dissociates in the Presence of Exogenous Leucine.
Ziegler CA, Freddolino PL.
mBio. 2023, 14: e0269022.
Genetic context effects can override canonical cis regulatory elements in Escherichia coli.
Scholz SA, Lindeboom CD, Freddolino PL.
Nucleic Acids Res. 2022; 50: 10360–75.
Escherichia coli YigI is a Conserved Gammaproteobacterial Acyl-CoA Thioesterase Permitting Metabolism of Unusual Fatty Acid Substrates.
Schmidt M, Proctor T, Diao R, Freddolino PL.
J Bacteriol. 2022; 204: e0001422.
HP1 oligomerization compensates for low-affinity H3K9me recognition and provides a tunable mechanism for heterochromatin-specific localization.
Biswas S, Chen Z, Karslake JD, Farhat A, Ames A, Raiymbek G, Freddolino PL, Biteen JS, Ragunathan K.
Sci Adv. 2022; 8: eabk0793.
Epistasis at the SARS-CoV-2 Receptor-Binding Domain Interface and the Propitiously Boring Implications for Vaccine Escape.
Rochman ND, Faure G, Wolf YI, Freddolino PL, Zhang F, Koonin EV.
mBio. 2022; 13: e00135-22.
PEPPI: Whole-proteome Protein-protein Interaction Prediction through Structure and Sequence Similarity, Functional Association, and Machine Learning.
Bell EW, Schwartz JH, Freddolino PL, Zhang Y.
J Mol Biol. 2022; 434: 167530.
Distinct heterochromatin-like domains promote transcriptional memory and silence parasitic genetic elements in bacteria.
Amemiya HM, Goss TJ, Nye TM, Hurto RL, Simmons LA, Freddolino PL.
EMBO J. 2022; 41: e108708.
For a list of publications at Google Scholar, click HERE