Ponzy Lu, Professor, Department of
Chemistry, University of
Pennsylvania, Philadelphia, PA
Biological Chemistry and Chair, College
Biochemistry Program, Director, Roy and Diana Vagelos
Scholars Program for the Molecular Life Sciences
Professor, born 1942; B.S.
California Institute of Technology (1964); Ph.D. Massachusetts
Institute of Technology (1970); Arthritis Foundation Postdoctoral
Fellow, Max-Planck Institut, Göttingen, Germany (1970-73); EMBO
Visiting Fellow, University of Geneva (1973, 74); CNRS Fellow,
Universite Aix-Provence I (1980).
Research
in Progress
In a collaboration
with A. Gewirtz of the Department of Medicine, we are exploring the use
of antisense molecular beacons to follow RNA transport and structure in
vivo.
With Don Baldwin of the Department
of Pathology and Laboratory Medicine we are developing novel approaches
to the use of microarray probe technology.
Research results
Since the lac operon has been
the paradigm for gene regulatory systems, our efforts have been focused
on obtaining structural information on the repressor operator complex.
To this end, a series of DNA binding domain fragments and variants have
been cloned and expressed for solution multinuclear multidimensional
NMR analysis, both as proteins and protein DNA complexes. In
collaboration with M. Lewis of the Department of Biochemistry and
Biophysics, the three-dimensional structures of (1) lac repressor
alone, (2) lac repressor with inducer, and (3) complexes of
intact tetrametic lac repressor, and operator DNA have been
solved.
An interesting result from our group
is the solution structure of A-tract DNA. This variation from the
average B form has been studied for two decades. Several X-ray
structures by other groups have been not consistent with the body of
solution properties of this family of DNA sequences. Our NMR
solution structure shows that the bend In the helix axis is actually 90
degrees away from the bend plane in the crystal structures. The
variation of nucleic acid structures as a function of sequence and
solvent conditions is an important consideration. In related
experiments, we have exploited the use of fluorescence depolarization
of bound ethidium bromide to investigate hydrodynamic size and shape of
RNA structures, e.g., tetraloops and ribozymes. These issues have
also become important as we are finding variations in mRNA
accessibility to antisense probes.
Chemistry Room 312 Laboratory Frieze - PhD students with dates of servitude.
Selected
Publications
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