Dr. Robert D. Hinrichsen

Bob Hinrichsen

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BA - 1972 Indiana University, Major: Zoology
MS - 1974 Indiana University, Major: Zoology
PhD - 1982 Indiana University, Major: Biology
Post doctorate - 1982-1987 - Laboratory of Molecular Biology, University of Wisconsin, Madison


Genetics and Molecular Biology; Cell Biology; Biochemistry


BIOL 113 Genetics in Modern Society
BIOL 123 Perspectives in Cell and Molecular Biology
BIOL 405/505 The Biology of the Cell
BIOL 662 Molecular Genetics of Eukaryotes
HNRC 202 Science core of Honor's College


The current subject of study in my laboratory has to do with the role of biological rhythms in the control of cellular behavior in Paramecium tetraurelia. My previous research involved the role of calcium and calmodulin in the control of cellular behavior and regulated exocytosis in the ciliated protozoan Paramecium tetraurelia. Paramecium was used as a model system for the investigation of cellular processes in excitable cells. This research included the study of the calcium-binding protein calmodulin and its role in both the activation of Ca2+-dep. K+ ion channels and the regulation of exocytosis. Genetic and cell biological studies have shown that calmodulin and the calmodulin-dep. protein phosphatase calcineurin are involved in the modulation of both of these processes.

More recent studies demonstrated the involvement of light in the behavioral response of Paramecium. Paramecium responds to a photo stimulus by changing the direction of the ciliary beat, an action that is correlated with the generation of an action potential. This response has been studied in several behavioral mutants of Paramecium tetraurelia and has allowed us to genetically dissect the pathway leading to the photoresponse of the cells. Genetic and cell biological studies are being conducted to further elucidate the cellular nature of this behavioral response.

Current research is concentrated on the role of biological rhythms in the control of cellular processes in Paramecium. We have recently demonstrated that both circadian and ultradian rhythms play a role in the frequency of spontaneous behavioral responses in cells. For example, Paramecium displays periodic changes in the frequency of behavioral responses, with an average periodicity of 50 minutes. This is an example of an ultradian rhythm. Importantly, we have shown that this periodicity is disrupted by low concentrations of LiCl, and that exogenous inositol reverses the effect. Using techniques in molecular biology (e.g. RNA interference) as well as cell biology and biochemistry has lead to the inositol depletion hypothesis as a means to explain these results. We have also shown that this frequency also has a circadian component as well that is altered when the protein kinase glycogen synthase kinase 3 is inhibited. The interplay of these two biological rhythms is currently being investigated. Finally, we have been able to shown that zinc has an essential role in the control of the circadian rhythm, and are investigating the control of zinc levels in the cell over a 24-hour period.

Selected Publications

Hinrichsen, R.D., A. Burgess-Cassler, B. Case-Soltvedt, T. Hennessey and C. Kung. 1986. Restoration by calmodulin of a Ca++-dependent K+ current missing in a mutant of Paramecium. Science 232:503-506.

Hinrichsen, R.D. and J. Schultz. 1987. Paramecium: A model system for the study of excitable cells. Trends in Neurosciences 11:27-32.

Schaefer, W., R.D. Hinrichsen, A. Burgess-Cassler, C. Kung, I. Blair and D.M. Watterson. 1987. A mutant Paramecium with a defective calcium-dependent potassium conductance has an altered calmodulin: A nonlethal selective alteration in calmodulin regulation. Proc. Nat. Acad. Sci. USA 84:3931-3935.

Erhlich, B., A. Jacobsen, R.D. Hinrichsen, L. Sayre and M. Forte. 1988. Paramecium calcium channels are blocked by a family of calmodulin antagonists. Proc. Nat. Acad. Sci. USA 85:5718-5722.

Schultz, J., S. Klump and R.D. Hinrichsen. 1990. Calcium and membrane excitation in Paramecium. In: Calcium as a second messenger in eukaryotic microbes. (ed. D. O'Day) pp. 124-150. American Society for Microbiology, Washington, D.C.

Hinrichsen, R.D., E. Wilson, T. Lukas, T. Craig, J. Schultz and D.M. Watterson. 1990. Analysis of the molecular basis of calmodulin defects that effect ion channel-mediated cellular responses: site specific mutagenesis and microinjection. J. Cell Biol. 111:2537-2542.

Preston, R., J. Kink, R.D. Hinrichsen, Y. Saimi and C. Kung. 1991. Calmodulin mutants and Ca2+-dependent channels in Paramecium. Ann. Rev. Physiol. 53:309-319.

Hinrichsen, R.D., M. Pollack, T. Hennessey and C. Russell. 1991. An intragenic suppressor of a calmodulin mutation in Paramecium: genetic and biochemical characterization. Genetics 129:717-725.

Hinrichsen, R.D., D. Fraga and M. Reed. 1991. Antisense oligodeoxynucleotides to the calmodulin gene alters the behavioral response in Paramecium. Proc. Nat. Acad. Sci. USA 89:8601-8605.

Schultz, J., C. Russell, J. Pohlner, R. D. Hinrichsen and S. Klumpp. 1992. Protein phosphatases in the protozoan Paramecium. In: "Advances in Protein Phosphatases." (ed. W. Merlevede)

Hinrichsen, R.D. and P. Blackshear. 1993. Regulation of peptide:calmodulin complexes by protein kinase C in vivo. Proc. Nat. Acad. Sci. USA 90:1585-1589.

Hinrichsen, R.D. 1993. Calcium and calmodulin in the control of cellular behavior and motility. Biochim. Biophys. Acta- Reviews in Cancer 155:277-293.

Hinrichsen, R.D. 1993. Calcium-Dependent Potassium Channels. R.G. Landes Company. Austin, TX.

Russell, C., D. Fraga and R.D. Hinrichsen. 1994. Extremely short 20-33 nucleotide introns are the standard length in Paramecium tetraurelia. Nucl. Acid Res.22:1221-1225.

Fraga, D. and R.D. Hinrichsen. 1994. The identification of a complex family of low molecular weight GTP-binding protein homologues from Paramecium tetraurelia by PCR cloning. Gene 147:145-148.

Hinrichsen, R.D., D. Fraga and C. Russell. 1995. The regulation of calcium Paramecium. In: "Advances in Second Messenger and Phosphoryaltion Research" (ed. A. Means) 30:311-338.

Reed, M., D. Fraga, D. Schwartz, J. Scholler and R.D. Hinrichsen. 1995. Synthesis and evaluation of nuclear targeting peptide-antisense oligodeoxynucleotide conjugates. Bioconjugate Chemistry 6:101-108.

Yano, J., D. Fraga, R.D. Hinrichsen and J. Van Houton. 1996. Effects of Calmodulin Antisense Oligonucleotides on Chemoresponse in Paramecium. Chemical Senses 21:55-58.

Fraga, D., J. Yano, M. Reed, R. Chuang, W. Bell, J. Van Houten and R.D. Hinrichsen, 1998. Introducing Antisense Oligonucleotides into Paramecium via Electroportation. J. Eur. Microbiol. 45: 582-588.

Hendel, E., P. Verhef, R.D. Hinrichsen and D. Fraga. 1999. The Half-Calmodulin Gene: A Study of the Minimal Structural Requirements of calmodulin in vivo Functions in Paramecium tetraurelia. Ohio J. Science 99(1): A-25.

Robert Hinrichsen and Joseph Trans. 2010. A Circadian Clock Regulates Sensitivity to Cadmium in Paramecium tetraurelia. Cell Biol. Toxicol. 26:379-389.

D. Fraga, I. Sehring, R. Kissmehl, M.Reiss, R. Gaines, R. Hinrichsen and H. Plattner. 2010. Protein Phosphatase 2B (PP2B, Calcineurin) in Paramecium: Partial Characterization Reveals that Two Members of the Unusually Large Catalytic Subunit Family Have Distinct Roles in Calcium-Dependent Processes. Eukaryotic Cell 9:1049-1063.

Robert Hinrichsen. 2010. The Frequency of the Behavioral Response in Paramecium tetraurelia Displays an Ultradian Rhythm: a Regulatory Role for the Inositol Signaling Pathway. Biol. Rhythms Res. 41: 457-475.

Hinrichsen R. D., Belsky, D., Jones, L. A. and Mialki, R. The frequency of the spontaneous behavioral response in Paramecium tetraurelia is simultaneously modulated by both ultradian and circadian rhythms. Biol. Rhythms Res. (in press).

Robert Hinrichsen and Christian Peters. A Genetic Dissection of the Photodispersal Response of Paramecium tetraurelia. Protist (in press).

Robert Hinrichsen. Biological Rhythms and Cell Behavior in Paramecium. In Protozoa: Biology, Classification and Role in Disease ed. Nadya Gotsiridze-Columbus (in press).