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Transposition is a complex genetic rearrangement process found in all organisms. Transposition is involved in genome evolution, with the spread of antibiotic resistance in bacteria, and with chromosome changes found in some cancers. Transposition is biochemically very similar to the HIV-1 provirus integration reaction. In addition, transposition is likely to offer new tools for rearranging DNA molecules in the laboratory. Thus, this process is of considerable interest.
My laboratory is deciphering the molecular details of transposition by studying a model bacterial transposon, Tn5. Tn5 encodes a protein called a transposase that catalyzes all the steps in transposition; transposase-transposon DNA binding, formation of a transposon nucleoprotein complex, cleavage of the transposon DNA free from surrounding DNA sequences, insertion of the transposon DNA into a new genetic site. For Tn5, all of these steps occur in a simple, defined, in vitro system. This allows us to study the detailed biochemical effects of various transposase and DNA target site mutations. In addition, we have, with the collaboration of Professor Ivan Rayment's laboratory, determined the three-dimensional structure of the transposase. This, coupled with the genetics and biochemistry, will generate a complete structure/function picture of the transposase and its target DNA sequences.
My laboratory is also interested in developing the Tn5 transposition system as a molecular genetic tool. Our long term goal is to develop methods that would allow in vitro combinatorial genetics to become a standard laboratory procedure.
Distinctions and awards
1963 Phi Beta Kappa, Williams College, Williamstown, MA
1963-1967 NIH predoctoral fellow, Johns Hopkins University, Baltimore, MD
1968-1969 NIH postdoctoral fellow, Harvard Medical School, Boston, MA
1970 Medical Research Foundation of Boston postdoctoral fellow, Harvard Medical School, Boston, MA
1972-1977 NIH Career Development Award, University of Wisconsin-Madison
1974-1978 Harry and Evelyn Steenbock Career Development award, University of Wisconsin-Madison
1984-1985 Faculty Star Award, University of Wisconsin-Madison
1985-present Evelyn Mercer Professor of Biochemistry and Molecular Biology, University of Wisconsin-Madison
1997 Vilas Associate Award, University of Wisconsin-Madison
2002 Spitze Land Grant Faculty Award, University of Wisconsin-Madison
2006 Arthur J. Maurer Extra Mile Award, University of Wisconsin-Madison
研究兴趣
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MBIOno. 2 (2024): e0278723-e0278723
Symbiosisno. 1 (2010): 67-73
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