(co-advised with Prof. M. Ashley Spies)

Sophie is fascinated by how tiny molecular machines (proteins!) change shape as they interact with DNA and small molecules in our cells; work that helps reveal how drugs can better target these dynamic systems. She uses single-molecule biophysics to watch individual proteins in action, uncovering mechanisms relevant to genome maintenance and drug design. When she’s not in the lab, you can find her traveling, doing yoga, on an adventure with her husky (Haichi!), or debating which horror movie reigns supreme (self-proclaimed connoisseur of all things spooky).

Projects:

Sophie studies how dynamic proteins help maintain genomic stability and how their movements can be harnessed for drug discovery. Using her single-molecule toolkit — including smTIRF, smFRET, CTFM, and mass photometry — she explores how the DNA-binding protein Replication Protein A (RPA) and its variant forms manage fragile, repetitive DNA sequences linked to neurodegenerative diseases. In a complementary project, she investigates glutamate racemase (MurI), an essential bacterial enzyme, to understand how small molecules alter its native dynamics and inhibit its function, guiding the design of new antibiotics.

Key Publications:

Granger SL, Sharma R, Kaushik V, Razzaghi M, Honda M, Gaur P, Bhat DS, Labenz SM, Heinen JE, Williams BA, Tabei SMA, Wlodarski MW, Antony E, Spies M. Human hnRNPA1 reorganizes telomere bound replication protein A. Nucleic Acids Res. 2024 Nov 11. 52(20). 12422-12437. PMCID PMC11551749.
Link https://doi.org/10.1093/nar/gkae834

Gaur P, Bain FE, Honda M, Granger SL, Spies M. Single molecule analysis of improved variants of the G-quadruplex recognition protein G4P. Int J Mol Sci. 2023 Jun 17. 24(12). PMCID PMC10299155.
Link https://www.mdpi.com/2346924

Sharma R, Sahoo SS, Honda M, Granger SL, Goodings C, Sanchez L, Künstner A, Busch H, Beier F, Pruett-Miller SM, Valentine MB, Fernandez AG, Chang TC, Géli V, Churikov D, Hirschi S, Pastor VB, Boerries M, Lauten M, Kelaidi C, Cooper MA, for the Undiagnosed Diseases Network, Nicholas S, Rosenfeld JA, Polychronopoulou S, Kannengiesser C, Saintomé C, Niemeyer CM, Revy P, Wold MS, Spies M, Erlacher M, Coulon S, Wlodarski MW. Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue. Blood. 2022 Feb 17, 139(7):1039-1051. PubMed PMID: 34767620.

Link https://doi.org/10.1182/blood.2021011980

For the full list of publications, check ORCiD.