Daniel Simmons, Ph.D.

Teaching

  • BISC 280* - Principles of Biotechnology
  • BISC 401* - Molecular Biology of the Cell
  • BISC 619* - Informational Macromolecules (Gene Expression Laboratory)
  • BISC 679* - Virology

*Access to this site has been restricted by Dr. Simmons

Research Interests

Our laboratory is interested in the structure and function of the simian virus 40 tumor antigen (T antigen) and of cellular proteins that interact with it in virus infected cells. T antigen is a multifunctional phosphoprotein synthesized early in SV40 infection. It is required for virus DNA replication and for the regulation of viral gene expression in infected cells. Its main functions are to serve.as the origin recognition protein and helicase so that replication can initiate at the origin and proceed bidirectionally along the circular DNA genome.

By using a multifaceted biochemical and genetic approach, we are investigating the fine structure and activity of various functional domains of T antigen and correlating this information to the biology of SV40. Our present efforts are focused on T antigen's ability to bind and unwind the origin of replication and on T antigen's role in the initiation and elongation phases of SV40 DNA replication. This viral protein forms a double hexamer over the origin and this structure serves as the helicase that structurally distorts then melts and unwinds the origin. It also functions to separate the DNA strands at replication forks. We have obtained evidence that cellular proteins topoisomerase I (topo I), DNA polymerase α/primase (pol/prim) and replication protein A (RPA) form a complex with hexamers of T antigen to initiate DNA replication. This complex is stabilized by numerous protein-protein and protein-DNA interactions and we are in the process of mapping and characterizing as many of these as possible. We have recently obtained detailed information about how topoisomerase I interacts with T antigen. By studying the effects of various proteins on the assembly of the complex, we have developed a model that describes the order of events at the origin to initiate DNA replication. We are presently testing various aspects of this model and asking how the complex changes during initiation and elongation of DNA replication.

Research Group

  • Erin Foster, B.A. - Graduate Student (B.A., Hood College). Mechanism of origin unwinding and initiation of DNA replication by SV40 T antigen.
  • Rupa Roy, B.S. - Research Associate II. Characterization of the Interactions Between SV40 Large T Antigen and Cellular Replication Factors.
  • Weiping Wang, B.S. - Graduate Student (B.S., Zhongshan University, China). Mechanism of helicase action by SV40 T antigen.

Selected Publications

Professor

Phone: (302) 831-8547

Fax: (302) 831-2281

Email: dsimmons@udel.edu

Office: 213 McKinly Lab

Lab: 257 McKinly Lab

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.S. - Colorado College
  • Ph.D. - California Institute of Technology
  • Postdoctoral - National Institutes of Health