We are interested in the structure, function, and design of protein-DNA complexes, focusing on the 50-1000 bp length scale. This is the biologically-relevant domain of multi-protein DNA complexes, DNA looping, chromatin, and DNA topology. We study the shapes of protein-nucleic acid complexes and DNA loops, the functional consequences of changes in shape, and the design and control of DNA and protein-DNA shape. We use molecular biology techniques like DNA ring closure, electrophoretic mobility shift assays, and footprinting to guide hypotheses, and then move on to characterization with fluorescence resonance energy transfer (FRET), single-molecule FRET, and atomic force microscopy (AFM). Accomplishments in this area include the identification of negatively supercoiled minicircles upon ring closure of short fragments bound by the TATA box binding protein (TBP), which led to a proposal on the coupling between chromatin remodeling during transcriptional activation and enhanced TBP binding. We also showed that DNA loops anchored by the Lac repressor can exist in at least two conformations that are distinguishable by bulk and single-molecule FRET. This has recently been expanded to include a systematic looping landscape that should provide valuable constraints for systems biology models of transcriptional regulation. Functional studies of gene regulation in bacteria complement our in vitro work. We have recently designed the world's smallest and stiffest DNA looping proteins, based on a coiled coil motif. Currently we are excited about designing DNA and proteins to form self-assembled protein-DNA nanostructures. Finally, we have applied interests in the hybridization thermodynamics of oligonucleotides containing modified chemistries, with an eye to improving the use of nucleic acids in diagnostics and therapeutics.
Current publication list including links to collaborators.
More detail: Here are two very large PDF files (1) and (2) that outline much of our work in the context of the field. These are informal, not comprehensive; I welcome any feedback you may have. Earlier versions were originally presented at a workshop at the Institute for Mathematics and its Applications (IMA), Univ. of Minnesota. This outdated but still illustrative PDF research description, and for historical curiousity an even older brief research description/resume are still available.
Practical applications of nucleic acid thermodynamics are done in collaboration with Celadon Laboratories, Inc.
Along with Ed Eisenstein, I am an advisor to the UMaryland iGEM team, which achieved (Au/Au/Ag/(Cu+Sn)/Au) medal status in 2014/15/16/17/18, their first five times competing in the international Genetically Engineered Machines Giant Jamboree. After a break in 2019, we are looking forward to the 2020 Jamboree -- LMK if you want to join the team!
I teach several general chemistry, biochemistry, and special interest courses. Here is a collection of general teaching resources, including figures created for several courses, and instructions, examples, and tutorials for Jmol/Rasmol/Pymol-based viewing of biomolecule PDB files. For recent courses, lecture notes and other resources are available mainly through the ELMS system at the University of Maryland, College Park.
Current Teaching with representative syllabi:
Chemistry 277, Bioanalytical Chemistry Laborator: Syllabus. The course covers fundamental analytical techniques like absorbance, fluorescence, titrations, and chemical kinetics. We also make nanoparticles, and we are experimenting in silico with the Einstein solid.
Chemistry 271, General Chemistry and Energetics: Syllabus.This is a course covering the traditional material for the second half of general chemistry, but given in the fourth semester of the undergraduate series, after organic chemistry instead of before. I also include special topics applications like DNA hybridization thermodynamics and the redox reactions driving anaerobic metabolism.
BSCI 338F is the seminar class associated with the iGEM team, vide supra.
At various times I have taught Biochem 461 (Biomolecules and Enzymes), 463 (Biochemistry and Physiology), 465 (Biological Information Processing), and parts of 462 (Metabolism).
Here is a TEDxUMD talk (15 min) from Spring, 2014 on my teaching philosophy. 8800+ views, although other faculty may sympathize with the fact that I have not walked it all the way through yet.
An archive of past exams for all of my chemistry and biochemistry courses. Use at your own risk.
I do not actively maintain links on these older pages, and some course materials were provided primarily through Blackboard and are not available here.
Biochemistry research here at the University of Maryland.
You can reach me at firstname.lastname@example.org
This page is designed using various tools, primarily Dreamweaver and hand-coding. Fossil remains of the code date to 1994.