Williams Laboratory

Single Molecule Studies of DNA Interactions

The Williams lab specializes in the development of single molecule methods for quantitatively probing the biophysical properties of DNA and RNA and for understanding the biophysics of their interactions with proteins and other DNA binding ligands. These methods are used to probe nucleic acid interactions in order to understand the role of these interactions in processes such as replication and transcription. Specifically, the lab studies single-stranded DNA binding proteins from viruses and bacteria, retroviral replication proteins such as HIV-1 nucleocapsid and Gag proteins, bacterial polymerases, small molecules that bind to DNA and may inhibit cellular replication, and nuclear proteins such as HMG proteins. At the heart of all of these studies is the search for the mechanism by which these proteins interact with DNA in order to alter its biophysical properties, thereby achieving their specific biological activity. In order to understand these mechanisms, these studies are done in collaboration with experts in each biological system, and the activities of the proteins are monitored in a variety of in vitro and in vivo studies to determine how the observed biophysical mechanism is manifested on the level of a more complete biological system.

News highlight:	Professor Williams featured in the Lumicks Dynamic Single-Molecule Symposium Series
Northeastern hosted The 11th International Retroviral Nucleocapsid and Assembly Symposium (IRNCAS) August 15-17, 2019!
Current Research
Retroviral and retrotransposon replication interactions - single molecule analysis of nucleic-acid protein interactions involved in replication of retroviruses such as HIV-1 and retrotransposons such as LINE1, as well as human innate immune proteins that give resistance to retroviruses. Dimerization by APOBEC3G on single-stranded DNA, which may inhibit HIV-1 replication, is illustrated on the left.
E. coli replication interactions - single molecule studies of polymerases and accessory proteins involved in E. coli DNA replication and repair. Studies of polymerization and exonucleolysis by E. coli pol III core polymerase complex are illustrated on the left.
Nucleosome accessibility in eukaryotic systems - single molecule studies of nucleosome-associated proteins such as HMGB architectural DNA bending proteins, including studies of nucleosome stability. The diagram on the left illustrates single molecule stretching and AFM experiments showing that HMGB proteins destabilize nucleosomes.
Small molecule interactions with DNA - detailed characterization of the energy landscape of small molecule-DNA interactions to optimize characteritics for potential anti-cancer drugs. The image at the left shows intercalation followed by covalent binding by phenanthriplatin.