Faculty Profile

CIRCADIAN (daily) CONTROL represents a very fundamental yet still very poorly understood feature of higher organisms. Jet lag is a symptom of the disruption of our circadian system. Indeed, most organisms--and even individual unicells and some bacteria--possess a temporal control mechanism over many biochemical and physiological processes. Our research is concerned with the basic molecular and cellular mechanisms responsible for these rhythms in the bioluminescent dinoflagellate Gonyaulax polyedra. Earlier studies included the first demonstration of the phase-dependency of shifting of the clock by light and its action spectrum, as well as the unique ability of inhibitors of protein synthesis to cause such phase-shifts. The circadian rhythm of bioluminescence involves a daily synthesis and destruction of two proteins involved in the biochemical reaction. While the amounts of these proteins increase and decrease by a factor of 10 on a daily basis, the mRNAs for these proteins remain at the same level day and night. Synthesis is thus controlled at the translational level, a feature so far unique to this system. Current studies are focused on the role of protein phosphorylation in the cycle: protein kinase and phosphatae inhibitors cause period changes. Circadian control of gene expression, and the identity of such clock-controlled genes, determined by microarrays, is also under study.

NSF: Bioluminescence: Molecular mechanisms and biochemical control

Harvard Undergraduate course: MCB 186
Circadian Biology: From cellular oscillators to sleep regulation
NAS-Chautauqua short course # 55: Circadian Biology: From Clock Genes and Cellular Rhythms to Sleep Regulation

Liu L, Hastings JW. Two different domains of the luciferase gene in the heterotrophic dinoflagellate Noctiluca scintillans occur as two separate genes in photosynthetic species.
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):696-701. Epub 2006 Nov 27. [PMID: 17130452]

Nealson KH, Hastings JW. Quorum sensing on a global scale: massive numbers of bioluminescent bacteria make milky seas.
Appl Environ Microbiol. 2006 Apr;72(4):2295-7. [PMID: 16597922]

Schultz LW, Liu L, Cegielski M, Hastings JW. Crystal structure of a pH-regulated luciferase catalyzing the bioluminescent oxidation of an open tetrapyrrole.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1378-83. Epub 2005 Jan 21. [PMID: 15665092]

Liu L, Wilson T, Hastings JW. Molecular evolution of dinoflagellate luciferases, enzymes with three catalytic domains in a single polypeptide.
Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16555-60. Epub 2004 Nov 15. [PMID:15545598]

Vadyvaloo V, Arous S, Gravesen A, Héchard Y, Chauhan-Haubrock R, Hastings JW, Rautenbach M. Cell-surface alterations in class IIa bacteriocin-resistant Listeria monocytogenes strains.
Microbiology. 2004 Sep;150(Pt 9):3025-33. [PMID: 15347760]

Ramnath M, Arous S, Gravesen A, Hastings JW, Héchard Y. Expression of mptC of Listeria monocytogenes induces sensitivity to class IIa bacteriocins in Lactococcus lactis.
Microbiology. 2004 Aug;150(Pt 8):2663-8. [PMID:15289562]

Hastings JW. Bacterial quorum-sensing signals are inactivated by mammalian cells.
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):3993-4. Epub 2004 Mar 15. [PMID: 15024108]

Vadyvaloo V, Snoep JL, Hastings JW, Rautenbach M. Physiological implications of class IIa bacteriocin resistance in Listeria monocytogenes strains.
Microbiology. 2004 Feb;150(Pt 2):335-40. [PMID: 14766911]

Okamoto OK, Hastings JW. Genome-wide analysis of redox-regulated genes in a dinoflagellate.
Gene. 2003 Dec 4;321:73-81. [PMID: 14636994]

Rossini C, Taylor W, Fagan T, Hastings JW. Lifetimes of mRNAs for clock-regulated proteins in a dinoflagellate.
Chronobiol Int. 2003 Nov;20(6):963-76. [PMID: 14680137]

Okamoto OK, Hastings JW. Novel dinoflagellate clock-related genes identified through microarray analysis.
Journal of Phycology. 2003; 39(3): 519-526.

Comolli JC, Fagan T, Hastings JW. A type-1 phosphoprotein phosphatase from a dinoflagellate as a possible component of the circadian mechanism.
J Biol Rhythms. 2003 Oct;18(5):367-76. [PMID: 14582853]

Hastings JW. Fifty years of fun.
J Biol Rhythms. 2001 Feb;16(1):5-18. [PMID: 11220778]

Comolli JC, Hastings JW. Novel effects on the Gonyaulax circadian system produced by the protein kinase inhibitor staurosporine.
J Biol Rhythms. 1999 Feb;14(1):11-9. [PMID: 10036988]

Knaust R, Urbig T, Li LM, Taylor W, Hastings JW. The circadian rhythm of bioluminescence in Pyrocystis is not due to differences in the amount of luciferase: A comparative study of three bioluminescent marine dinoflagellates.
Journal of Phycology. 1998; 34(1): 167-172.

Mittag M, Eckerskorn C, Strupat K, Hastings JW. Differential translational initiation of lbp mRNA is caused by a 5' upstream open reading frame.
FEBS Lett. 1997 Jul 14;411(2-3):245-50. [PMID: 9271214]

Techel D, Chuang E, Lee DH, Comolli J, Hastings JW. Changes in the ultrastructural localization of mRNA for a circadian regulated protein.
Mol Mar Biol Biotechnol. 1996 Dec;5(4):241-8. [PMID: 8983193]

Comolli J, Taylor W, Rehman J, Hastings JW. Inhibitors of serine/threonine phosphoprotein phosphatases alter circadian properties in Gonyaulax polyedra.
Plant Physiol. 1996 May;111(1):285-91. [PMID: 8685268]

Mittag M; Hastings JW.  Exploring the signaling pathway of circadian bioluminescence.
Physiologia Plantarum. 1996; 96(4): 727-732.

Books, Reviews, Chapters, etc.

Hastings JW. The Gonyaulax clock at 50: translational control of circadian expression.
Cold Spring Harb Symp Quant Biol. 2007;72:141-4. Review. [PMID:18419271]

Hastings JW, Morin JG. Photons for reporting molecular events: green fluorescent protein and four luciferase systems.
Methods Biochem Anal. 2006;47:15-38. Review. [PMID: 16335708]

Hastings JW. Fifty years of fun.
J Biol Rhythms. 2001 Feb;16(1):5-18. [PMID: 11220778]