Probing Protein–DNA Recognition, Binding, and Function with Nonlinear Spectroscopy and Single-Molecule Optical Techniques

by Prof. Andy Marcus (University of Oregon)

Monday 6 Jul 2026, 11:00 → 13:00 Europe/Rome

1/1-2 - Aula "C. Voci" (Dipartimento di Fisica e Astronomia - Edificio Marzolo)

Lunedi 6 luglio 2026 - Ore 11 Aula Voci

 

Prof. Andy Marcus

University of Oregon

 

 

Title: 

Probing Protein–DNA Recognition, Binding, and Function with Nonlinear Spectroscopy and Single-Molecule Optical Techniques 

 

Abstract: 

Proteins that interact with DNA must locate specific target sites within the genome, recognize appropriate structural and sequence features, and carry out tightly regulated functional processes such as replication, transcription, and repair. Despite extensive study, the molecular mechanisms that couple DNA recognition and binding to biological function remain incompletely understood, particularly on the time and length scales relevant to dynamic cellular environments.

In this work, we employ a combination of nonlinear spectroscopic methods and single-molecule optical techniques to investigate the mechanisms of protein–DNA recognition, binding, and function. Multidimensional fluorescence-detected spectroscopy provides access to coherent and incoherent dynamical processes, enabling us to resolve heterogeneous structural ensembles and characterize couplings between electronic states in labeled nucleic acid systems. Complementary single-molecule approaches allow direct observation of stochastic binding events, conformational transitions, and functional activity in real time, revealing distributions of pathways and intermediates that are obscured in ensemble measurements.

By integrating these approaches, we map the free-energy landscapes that govern protein–DNA interactions, linking structural fluctuations and binding specificity to functional outcomes. We illustrate these principles through studies of specific systems, including the T4 bacteriophage single-stranded DNA binding protein (gp32), the T4 clamp–clamp loader complex, and the E. coli lactose repressor–operator system. These examples provide new insights into how proteins recognize their DNA targets and how this recognition couples to biological function, offering a more complete physical picture of the molecular machines that underlie genome expression.