Source: Interfolio F180

David Millar

Department of Integrative Structural and Computational Biology


Research Focus

Biophysical Chemistry

The focus of our research is on the dynamic structural changes that occur during cellular rearrangements of DNA and during ribozyme catalysis. One project is aimed at understanding the proofreading process that underlies the high DNA replication fidelity of DNA polymerases. Using time-resolved and single-molecule fluorescence methods, in conjunction with site-directed mutagenesis procedures, we are elucidating the molecular mechanisms that control the movement of a DNA substrate between the polymerization site of the enzyme and a separate 3'-5' exonuclease site used in proofreading. We use similar methods to monitor large-scale conformational changes that occur during the catalytic cycle of the hairpin ribozyme, a small endonucleolytic RNA that serves as a model for much larger catalytic RNA molecules. By means of fluorescence resonance energy transfer (FRET) between appropriately placed fluorescent probes, we follow the docking of the substrate-binding and catalytic domains of the ribozyme in real time and identify nucleotides that stabilize the catalytically active docked conformation. Single-molecule FRET methods are also being applied to Holliday junctions, four-stranded DNA structures that are formed during the course of genetic recombination and related DNA repair events.


Ph.D., California Institute of Technology, 1982
B.S. (Chemistry), University of Melbourne, 1976

Professional Experience

Editorial Board, Biophysical Journal.
Elected member, Council of the Biophysical Society. ?
Member, Macromolecular Structure and Function C study section, NIH.

Awards & Professional Activities

1976 Professor Kernot Prize in Chemistry, University of Melbourne
1981 Herbert Newby McCoy Award for Graduate Research, CalTech
1983 Fullbright Fellowship, Fullbright
1987 Queen Elizabeth II Fellowship

Selected Publications

Millar, D. P.; Singh, A. R.; Pauszek, R. F.; Millar, D. P.; Lamichhane, R. Author response: Single-molecule view of coordination in a multi-functional DNA polymerase. eLife 2020.

Lamichhane, R.; Hammond, J. A.; Pauszek, R. F.; Anderson, R. M.; Pedron, I.; van der Schans, E.; Williamson, J. R.; Millar, D. P. A DEAD-box protein acts through RNA to promote HIV-1 Rev-RRE assembly. Nucleic Acids Research 2017, 45, 4632-4641.

Lamichhane, R.; Liu, J. J.; Pljevaljcic, G.; Maier, K.; van der Schans, E.; Katritch, V.; Stevens, R. C.; Wuthrich, K.; Millar, D. P. Single-molecule view of basal activity and activation mechanisms of the G protein-coupled receptor ß2AR. Proceedings of the National Academy of Sciences of the United States of America 2015, 112, 14254-14259.