Lydia Freddolino, PhD

Lydia Freddolino
Professor of Biological Chemistry
Professor of Computational Medicine and Bioinformatics
Medical School
University of Michigan
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0600
[email protected]
Available to mentor
Lydia Freddolino, PhD
Lydia Freddolino
Professor
  • About
  • Links
  • Qualifications
  • Research Overview
  • Recent Publications
  • Manage Your Profile

  • About

    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.

    Links

    • Freddolino Lab

    Qualifications

    • Postdoctoral fellow
      Columbia University, Systems Biology, United States
      2011 - 2014
    • Postdoctoral researcher
      Princeton University, Molecular Biology, United States
      2009 - 2011
    • PhD
      University of Illinois at Urbana-Champaign, Urbana, IL, United States
      2004 - 2009
    • BS
      California Institute of Technology, Pasadena, CA, United States
      2000 - 2004

    Research Overview

    * Interplay of protein occupancy, chromosomal structure, and gene regulation in bacteria
    * New mechanisms of bacterial transcriptional regulation
    * High-performance methods for protein structure prediction
    * Functions and physiological roles of poorly annotated proteins

    Recent Publications

    See All Publications
    • Journal Article
      ShapeME: A Tool and Web Front-end for De Novo Discovery of Structural Motifs Underpinning Protein-DNA Interactions
      Schroeder JW, Ramirez V, Wolfe MB, Freddolino L. Journal of Molecular Biology, 2026 Sep 15; 438 (18): DOI:10.1016/j.jmb.2026.169810
      PMID: 41997213
    • Journal Article
      Escherichia coli and Salmonella: their past, present, and future in scientific research and publications
      Bernstein HD, Detweiler CS, Freddolino L, Karp P, Lovett ST, Slauch JM, Torres AG. Microbiology and Molecular Biology Reviews Mmbr, 2026 Jun 25; 90 (2): e0010526 DOI:10.1128/mmbr.00105-26
      PMID: 42227755
    • Journal Article
      Whole-proteome structure/function prediction in Uropathogenic E. coli reveals previously missed host-microbe and microbe-phage interaction pathways.
      Peng C, Schreiber H, Zhang C, Liu Q, Hultgren S, Freddolino L. bioRxiv, 2026 Jun 16; DOI:10.64898/2026.06.16.732597
      PMID: PMC13308129
    • Preprint
      Defining the Candidozyma auris pan-genome and essentiality.
      Hale JJ, Larkin AJ, Rapala JR, Hurto R, Zhao G, Elson BE, Freddolino L, Snitkin ES, O'Meara TR. 2026 May 13; DOI:10.64898/2026.05.12.724661
      PMID: 42182103
    • Journal Article
      Polyphosphate modulates the stress-responsive formation of functional RNA-protein condensates in bacteria and mammalian cells
      Guan J, Hurto RL, Rai A, Bhattrai J, Azaldegui CA, Ortiz-Rodríguez LA, Liu Q, Biteen JS, Freddolino L, Jakob U. Plos Biology, 2026 Apr 27; 24 (4): DOI:10.1371/journal.pbio.3003775
      PMID: 42044170
    • Journal Article
      Deep-learning-based single-domain and multidomain protein structure prediction with D-I-TASSER
      Zheng W, Wuyun Q, Li Y, Liu Q, Zhou X, Peng C, Zhu Y, Freddolino L, Zhang Y. Nature Biotechnology, 2026 Apr 1; 44 (4): 641 - 653. DOI:10.1038/s41587-025-02654-4
      PMID: 40410405
    • Journal Article
      A graphic and command line protocol for quick and accurate comparisons of protein and nucleic acid structures with US-align
      Zhang C, Freddolino L, Zhang Y. Nature Protocols, 2026 Feb 1; 21 (2): 517 - 541. DOI:10.1038/s41596-025-01189-x
      PMID: 40604267
    • Journal Article
      Alternative Conformation Prediction Using Deep Learning With Multi-MSA Strategy and Structural Clustering in CASP16
      Wuyun Q, Liu Q, Ni W, Peng C, Zhang Z, Zhou X, Hu G, Freddolino L, Zheng W. Proteins Structure Function and Bioinformatics, 2026 Jan 1; 94 (1): 348 - 361. DOI:10.1002/prot.70059
      PMID: 41014267

    Featured News & Stories

    cells floating green black background strings many floating in backdrop
    Health Lab

    Scientists discover that bacteria use an understudied polymer found in all life to protect cell functions during stress

    New study discovers that polyphosphate, a molecule that exists in all lifeforms but has to date been hard to study, could be a fundamental element worth exploring, say Michigan Medicine researchers.
    Alan Boyle, Lydia Freddolino and Lam (Alex) Tsoi
    Department News

    Alan Boyle, Lydia Freddolino and Lam (Alex) Tsoi receive promotions!

    The Gilbert S. Omenn Department of Computational Medicine and Bioinformatics is pleased to announce the following faculty promotions
    Headshots of five Biological Chemistry faculty promoted in 2025
    Department News

    Five Biological Chemistry faculty members receive promotions in 2025

    Biological Chemistry faculty members Ryan Baldridge, PhD, Kevin Bohannon, PhD, Lydia Freddolino, PhD, Tobias Giessen, PhD, and Jeremy Schroeder, PhD, have been promoted.
    RNA strand in purple on black background
    Health Lab

    A structural biologist weighs in on the tricky task of determining RNA’s shape

    A recent article in Nature details why the quest to determine the shapes of RNA is difficult even for artificial intelligence.
    headshot of Yulduz Rakibova
    Department News

    Congratulations to Yulduz Rakibova, PhD

    Biological Chemistry PhD student Yulduz Rakibova of the Freddolino lab defends her doctoral dissertation.
    Department News

    U-M Bioinformatics excels at CASP15

    U-M Bioinformatics excels at CASP15