Professor Emeritus of MCD Biology
B.A. Swarthmore College
M.A., Ph.D., Princeton University
Molecular Genetic Analysis of Circadian Clock Mechanisms
Daily fluctuations in biochemical, physiological, and behavioral parameters have been known for many years. One class of these daily rhythms, known as circadian rhythms, persists in the laboratory in constant environmental conditions and is under the control of an endogenous timing mechanism referred to as a biological (circadian) clock.
Our primary research effort has been to develop a system of circadian clock mutants in Neurospora crassa that can be used as a primary tool in understanding the cellular and biochemical organization of the clock and identifying specific molecular processes that control circadian oscillations. In Neurospora, the clock controls circadian rhythms of DNA and RNA synthesis, carbon dioxide production, and the activities of a number of enzymes, as well as an easily monitored rhythm of asexual spore formation.
We have isolated clock mutants in which the period length of the circadian oscillation is either shorter or longer than normal. These mutants map to six different genetic loci. One locus, called frq, is especially interesting because almost half of the mutants isolated occur in this gene, because these mutants show a gene-dosage effect on period length, and because mutations at this locus cause the clock to run either faster or slower. The frq locus has been cloned and sequenced and appears to code for a transcriptional regulatory factor. Efforts to clone and sequence other clock genes are in progress.
Morgan, L.W. and J.F. Feldman. 2001. Epistatic and synergistic interactions among circadian clock mutations in Neurospora crassa. Genetics 159: 537-543.
Morgan, L.W., Feldman, J.R., and Bell-Pedersen, D. Genetic interactions between clock mutations in Neurospora crassa. Phil. Trans. Royal Soc. Lond. B. Biol. Sci. 356: 1717-24 (2001).
Lewis, M.T., Morgan, L.W., and Feldman, J. F. Analysis of frequency (frq) clock gene homologs: evidence for a helix-turn-helix transcription factor. Mol. Cell. Biol. 253(4): 401-414 (1997).
Lewis, M.T. and Feldman, J.F. Evolution of the frequency (frq) clock locus in Ascomycete fungi. Molec. Biol. Evol. 13: 1233-41 (1996).
Morgan, L.W., and Feldman, J.F. Isolation and characterization of a temperature-sensitive circadian clock mutant of Neurospora crassa. Genetics 146(2): 525-530 (1997).
Lewis, M. and Feldman, J.F. The putative frequency (frq) clock protein of Neurospora crassa contains sequence elements that suggest a nuclear transcriptional regulatory role. Prot. Seq. and Data Analysis 5: 315-32 (1993).
Loros, J. J. and Feldman, J. F. Loss of temperature compensation in a circadian clock mutant of Neurospora. J. Biol. Rhythms 1: 187-198 (1986).
Feldman, J. F. and Dunlap, J. C. Neurospora crassa: A unique system for studying circadian rhythms. Photochem. Photobiol. Rev. 7: 319-368 (1983).
Feldman, J. F. Genetic approaches to circadian clocks. Ann. Rev. Plant Physiol. 33: 583-608 (1982).