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Peter H. von Hippel

Peter H. von Hippel

Emeritus, Chemistry and Biochemistry
Member, IMB

Ph.D., Massachusetts Institute of Technology
M.S., Massachusetts Institute of Technology
B.A., Massachusetts Institute of Technology

Email
Office: Klamath Hall Room 215A
Office Phone: 541-346-6097
Lab: Klamath Hall Room 205
Lab Phone: 541-346-4212

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Research Interests

Professor von Hippel is retired from teaching, but continues to run fully active and funded research program(s). Applications from potential postdoctoral fellows and undergraduate research participants are welcome.

My associates and I are using physical biochemical approaches to study what might be called the molecular basis of gene expression. Most of our experimental work is concerned with the function and regulation of the complexes that control DNA transcription and replication, with studies focused primarily on transcription with the E. coli DNA-dependent RNA polymerase and its regulatory factors and on replication with the seven-protein bacteriophage T4-coded DNA replication system. Comparative studies are also underway using selected components of some equivalent eukaryotic systems.

In transcription our group is studying the transcription cycle, both at the overall operon level and at the level of the various steps of the single-nucleotide addition-excision cycle. At the operon level we are studying regulatory interactions that control activation and repression at initiation, the kinetics of elongation, and the molecular bases of the elongation-termination decision at both intrinsic and rho-dependent transcription terminators, together with the mechanisms of action antitermination factors. We have recently completed a study of E. coli transcription termination factor rho, in terms of its function as a specific RNA-DNA helicase and as a transcript terminator. Our antitermination studies have focussed on the mechanisms of action of the N protein of phage lambda in N-dependent antitermination systems. At the single-nucleotide addition-excision cycle level we are using various kinetic techniques to understand the molecular origins of transcriptional processivity and fidelity.

In replication our work began with studies of the cooperative binding of the T4 gene 32 (single-stranded DNA binding) protein to the single-stranded DNA (and RNA). This then led us to examine the interactions of the other components of the system, including those of the DNA polymerase with the primer-template and the polymerase accessory proteins. These studies have shown that the basically nonprocessive T4 DNA polymerase can be rendered fully processive by means of "sliding-clamp" processivity factor, and that the role of the other accessory proteins is to carry out the specific and ATP-dependent loading of the processivity factor onto the polymerase at the primer-template junction in the replication fork. The resulting complex can carry out leading strand DNA replication with essentially in vivo rate, fidelity, and processivity. The helicase of the T4 DNA replication system functions as a hexamer and, in combination with a single T4 primase subunit, forms a stable primosome subassembly. We have recently also shown a direct coupling between the polymerase and the helicase. This complex alone, if properly loaded onto a model replication fork, can carry out processive synthesis on a double-stranded DNA construct at the physiological rate. The mode of assembly of these components into a fully functional and coupled DNA replication system is currently being studied.

In all these studies we emphasize the elucidation of the detailed mechanisms and general principles of protein-nucleic acid and protein-protein interactions that underlie the function of these biologically central complexes. Over the last few years, in collaboration with the laboratory of Andrew Marcus, we have developed new spectroscopic and single-molecule biophysical approaches to studying the mechanisms and dynamics of various components of the above replication and transcription systems. For details, see recent publications, and also the website of IMB Associate Member Andrew Marcus.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

Single-molecule FRET and linear dichroism studies of DNA breathing and helicase binding at replication fork junctions.
Phelps C, Lee W, Jose D, von Hippel PH, Marcus AH
Proceedings of the National Academy of Sciences of the United States of America 2013
Fifty years of DNA "Breathing": Reflections on old and new approaches.
von Hippel PH, Johnson NP, Marcus AH
Biopolymers 2013
Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.
Widom JR, Rappoport D, Perdomo-Ortiz A, Thomsen H, Johnson NP, von Hippel PH, Aspuru-Guzik A, Marcus AH
Nucleic acids research 2013
Breathing fluctuations in position-specific DNA base pairs are involved in regulating helicase movement into the replication fork.
Jose D, Weitzel SE, von Hippel PH
Proceedings of the National Academy of Sciences of the United States of America 2012
Assembly and subunit stoichiometry of the functional helicase-primase (primosome) complex of bacteriophage T4.
Jose D, Weitzel SE, Jing D, von Hippel PH
Proceedings of the National Academy of Sciences of the United States of America 2012
Fitting experimental transcription data with a comprehensive template-dependent modular kinetic model.
Greive SJ, Dyer BA, Weitzel SE, Goodarzi JP, Main LJ, von Hippel PH
Biophysical journal 2011
Development of a "modular" scheme to describe the kinetics of transcript elongation by RNA polymerase.
Greive SJ, Goodarzi JP, Weitzel SE, von Hippel PH
Biophysical journal 2011
DNA conformational changes at the primer-template junction regulate the fidelity of replication by DNA polymerase.
Datta K, Johnson NP, von Hippel PH
Proceedings of the National Academy of Sciences of the United States of America 2010
The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing.
Warf MB, Diegel JV, von Hippel PH, Berglund JA
Proceedings of the National Academy of Sciences of the United States of America 2009
Spectroscopic studies of position-specific DNA "breathing" fluctuations at replication forks and primer-template junctions.
Jose D, Datta K, Johnson NP, von Hippel PH
Proceedings of the National Academy of Sciences of the United States of America 2009