Nancy C Horton
The Horton lab uses biophysical, biochemical, and molecular biology to study protein-DNA interactions and filament formation by enzymes. Current projects include the investigation of mechanisms of disease caused by the Human Parvovirus B19, and advantages of filament formation by enzymes such as the sequence specific DNA endonuclease SgrAI, and the important metabolic enzyme PFK.
The Horton lab uses a variety of biochemical and biophysical methods to investigate DNA binding proteins. Recent projects include the discovery of a novel mechanism of regulation of enzyme activity using filamentation. Filamentation, or self-association into polymers of varied lengths, by enzymes has only recently been appreciated as a widespread phenomenon, although the purpose of filamentation is not known in most cases. We discovered this phenomenon in 2010 in a sequence specific endonuclease, SgrAI, and have now determined its high resolution structure via cryo-electron microscopy. We have also performed a full kinetic analysis showing that filamentation greatly expedites the activation of the enzyme, and also allows for the sequestration of enzyme activity onto only a subset of available substrates. The other major project in the lab concerns the triggering of autoimmune diseases in genetically susceptible individuals. We study proteins from the human parvovirus B19, a virus which often precedes the development of autoimmune diseases like rheumatoid arthritis, autoimmune hepatitis, and lupus. We study how these proteins interact with cellular components to modulate the immune system into loss of self-tolerance.