William T. Keeton Professor of Biology (active in teaching, but not research)
Publications | Research | Faculty
Background:
Professor Joseph M. Calvo is the William T. Keeton Professor of Biology in the Section of Biochemistry, Molecular and Cell Biology. He received a B.A. degree from Whitman College, Walla Walla, Washington, in 1956 and then studied at the University of Freiburg, West Germany as a Fulbright Scholar from 1956-57. He received a Ph.D. in Chemistry from Washington State University in 1962 and from 1962-64 was a Research Associate at Cold Spring Harbor working with H. E. Umbarger. In 1964 he joined the Cornell faculty and became a full professor in 1979. Professor Calvo is a member of the American Society of Microbiology.
Enteric bacteria such as E. coli periodically experience rapid and dramatic changes in environment. To cope with such changes, these organisms have evolved complex regulatory mechanisms that control expression of most operons. Our studies of one of these operons, the ilvIH operon, have led us to an unexpected conclusion, namely, that leucine is part of a more global regulatory circuit that helps E. coli coordinate the activities of a number of different operons. Operons that are related through this regulatory circuit include several involved in amino acid biosynthesis, amino acid degradation, the transport of amino acids and peptides, and the synthesis of hair-like projections called pili.
The ilvIH operon of E. coli encodes an isozyme catalyzing the first step unique to branched chain amino acid biosynthesis. Growth of cells in the presence of leucine causes transcription from the ilvIH promoter to be repressed. The basis of this repression is the following. Transcription from the ilvIH promoter requires the presence of a protein called Lrp, encoded by the lrp gene. Leucine causes repression by interfering with the stimulation caused by Lrp. We have purified Lrp to homogeneity and have used it to define sites at which Lrp binds to the ilvIH promoter/regulatory region and to study transcription of the operon in vitro. Lrp binds to multiple sites upstream of the promoter, over a wide region of several hundred base pairs. We are trying to understand how binding over such a wide region activates transcription of the operon. In addition, we have isolated mutations that affect Lrp function and are using these mutations to learn something about functional domains of the protein.
From our work and that of others it is becoming clear that the regulatory system based upon Lrp is both flexible and far reaching. Lrp stimulates expression of some operons and that stimulation is negated by leucine. In other cases, Lrp represses operons and that repression is negated by leucine (leading to induction by leucine). In one case, Lrp represses an operon and that repression requires leucine. In still other cases, Lrp regulates an operon and this regulation is not affected by leucine. Uncovering the basis for the apparent flexibility of this regulatory system will be a challenge.
Click here to view Dr. Calvo's PubMed listings.
S.A. Zahler and J.M. Calvo (1994). Transcription attenuation. Charging it cancels the order. Current Biology 4, 73-75.
Q. Wang, J. Wu, D. Friedberg, J. Platko and J.M. Calvo (1994). Regulation of the Escherichia coli lrp gene. J. Bacteriol. 176, 1831-1839.
J.M. Calvo and R.G. Matthews (1994). The leucine-responsive regulatory protein (Lrp), a global regulator of metabolism in Escherichia coli. Microbiol. Rev. 58, 466-490.
Q. Wang, F.G. Albert, J.M. Calvo and J.N. Anderson (1994). Sequence determinants of DNA bending in the ilvIH promoter and regulatory region of Escherichia coli. Nucleic Acids Res. 22, 5753-5760.
D. Friedberg, J.V. Platko, B. Tyler and J.M. Calvo (1995). The amino acid sequence of Lrp is conserved in four enteric bacteria. J. Bacteriol. 177, 1624-1626.
Y. Cui, Q. Wang, G.D. Stormo and J.M. Calvo (1995). A consensus sequence for binding of Lrp to DNA. J. Bacteriol. 177, 4872-4880.
Y. Cui, M.A. Midkiff, Q. Wang and J.M. Calvo (1996). The leucine-responsive regulatory protein (Lrp) from Escherichia coli: Stoichiometry and minimal requirements for binding to DNA. J. Biol. Chem. 271, 6611-6617.
J. R. Landgraf and J. M. Calvo (1996). The effect of nutrition and growth rate upon Lrp levels in Escherichia coli. J. Bacteriol. 178: 6930-6936.