User:Photeros/J. Woodland Hastings

Woody Hastings
J. Woodland (“Woody”) Hastings (born on March 24, 1927 in New Jersey) is a leader in the field of photobiology, especially bioluminescence, and is one of the founders of the field of circadian biology (circadian rhythms). He is the Paul C. Mangelsdorf Professor of Natural Sciences (Emeritus) in the Department of Molecular and Cellular Biology at Harvard University. He has published over 400 papers and co-edited three books.

Hastings research on bioluminescence has principally focused on bacterial luminescence (over 150 papers) and dinoflagellates (over 80 papers). In addition to bacteria and dinoflagellates, he, with his students and colleagues, has published papers on the biochemical and molecular mechanisms of light production in such diverse organisms as fungi], [[cnidarians, ctenophores, polychaetes, insects (fireflies and dipterans), ostracod crustaceans, millipedes, tunicates, and fishes with bacterial light organs. His laboratory produced: 1) the first evidence for quorum sensing in bacteria (initially involving luminescent proteins, but has since expanded to bacterial toxins and other products), 2) early evidence of the molecular mechanisms of circadian clock regulation in organisms (first using dinoflagellate luminescence and then expanded to other cellular proteins),  and 3) some of the initial studies of energy transfer in green fluorescent proteins (GFP) in cnidarian luminescence.

His Career

 * 1948-1951: Hastings began his graduate studies at Princeton University (Princeton, NJ) in 1948 in the laboratory of E. Newton Harvey, the world leader of luminescence studies at the time, and focused on the role of oxygen in the luminescence of bacteria, fireflies, ostracod crustaceans and fungi. He received his PhD in 1951.


 * 1951-1953: He then joined the lab of William D. McElroy, another student of Harvey’s, at Johns Hopkins University (Baltimore, MD) where he discovered both the stimulatory effects of coenzyme A and gating control by oxygen of firefly luminescence, and that flavin is a substrate in bacterial luminescence.


 * 1953-1957: In 1953 he joined the faculty in the Department of Biological Sciences at Northwestern University (Evanston, IL). In 1954 he began a long collaboration with Beatrice Sweeney, who was then at the Scripps Institution of Oceanography (La Jolla, CA), in elucidating the cellular and biochemical mechanisms of luminescence in the unicellular dinoflagellate Lingulodinium polyedrum (formerly Gonyaulax polyedra). A byproduct of this initial research was their discovery of circadian control of the luminescence.


 * 1957-1966: Hastings next took a faculty position in the Biochemistry Division of the Chemistry Department at the University of Illinois at Urbana–Champaign (Urbana, IL) where he continued his focus on dinoflagellate and bacterial luminescence and dinoflagellate circadian rhythms.


 * 1966-present: Hastings joined the faculty of Harvard University as Professor of Biology in 1966 and where he remains as an emeritus professor. During this period he continued and expanded his studies of circadian rhythms in dinoflagellates and luminescence in bacteria, dinoflagellates and other organisms. He was elected to the National Academy of Sciences in 2003 and received the prestigious Farrell Prize in Sleep Medicine for his work on circadian rhythms in 2006.


 * For over 50 years he has also had an affiliation with the Marine Biological Laboratory in Woods Hole, MA. He was the director of the renowned Physiology Course there from 1962-.1966, and served as a trustee from 1966-1970.

Research Interests
Because of his immense curiosity, his propensity to encourage the same from his students, and his motivation to gain basic knowledge, Hastings and his colleagues have discovered numerous important aspects of the biological world that have had profound societal impacts.


 * Luminescent Bacteria: Hastings investigations of luminous bacteria have led not only to basic discoveries of the biochemical mechanisms involved in their light production, the discovery of a flavin to be a substrate in its luciferase reaction, the determination of gene regulation of the luciferases, but also the first evidence for quorum sensing, an important form of bacterial communication. In quorum sensing (initially termed autoinduction), the bacteria release into the medium a substance, the autoinducer, that, once the concentration of this substance reaches a critical level, which is a measure of the number of bacteria in a limited area, transcription of specific other genes that had been repressed are turned on.  Once the sequenced autoinducer gene was found to occur widely in gram-negative bacteria quorum sensing became accepted in the early 1990s.  Now we know that, like the luciferase proteins, in many pathogenic bacteria there is delayed production of toxins, which serve to greatly augment their pathogenicity.  By curtailing their toxin output until the bacterial populations are substantial these bacteria can generate massive quantities of toxin quickly and thereby swamp the defenses of the host.


 * Luminescent Dinoflagellates: Beginning in 1954 at Northwestern University Hastings and his students and colleagues have been studying cellular and molecular aspects of bioluminescence in dinoflagellates [especially Lingulodinium polyedrum (formerly Gonyaulax polyedra)]. They have been elucidating the structures of the luciferins and luciferases, the organization and regulation of their associated genes, temporal control mechanisms, and the actual subcellular identity and location of the light emitting elements, which they termed scintillons.  They demonstrated that the reaction is controlled by a drop in pH when an action potential leads to the entry of protons via voltage-activated membrane channels in the scintillons.  Through immunolocalization studies Hastings lab showed that scintillons are small peripheral vesicles (0.4 μm) that contain both the luciferase and the luciferin-binding protein.  Recently their lab has found that the luciferase gene in Lingulodinium polyedrum and other closely related species contains three homologous and contiguous repeated sequences in a kind of “three-ring circus with the same act in all three.”  However, another luminescent, but heterotrophic, dinoflagellate, Noctiluca scintillans, has but a single protein, which appears to possess both catalytic and substrate binding properties in a single, rather than separate proteins.


 * Dinoflagellate Circadian Rhythms: Using Lingulodinium polyedrum as a model, Hastings has spear-headed our understanding of the molecular mechanisms involved in control of circadian rhythms, which in humans are involved in sleep, jet-lag and other daily activities.  His lab has shown that the rhythm of bioluminescence involves a daily synthesis and destruction of proteins.  Because the mRNAs that code for these proteins remain unchanged from day to night, the synthesis of these proteins is controlled at the translational level.  This work has now been expanded to other proteins in the cell.  On the other hand, short pulses of inhibitors of synthesis of these proteins results in phase shifts of the circadian rhythm, either delays or advances, depending when the pulse is administered.  At still another level, protein phosphorylation inhibitors also influence the period of the rhythm.


 * Other luminescent systems: Early in his career Hastings developed techniques to quantify the level of oxygen required in a luminescent reaction for several different species including bacteria, fungi, fireflies and ostracod crustaceans. A direct result of this work showed that oxygen gating is the mechanism for firefly flashing. In other work when he was in the McElroy lab he examined the basic biochemical mechanism of firefly luciferase and demonstrated that coenzyme A stimulates light emission.  Still other studies associated with his lab first demonstrated that the green in vivo coelenterate bioluminescence occurs because of energy transfer from the luminescent molecule (aequorin), which alone emits blue light, to a secondary green emitter which they termed green fluorescent protein (GFP).  Once characterized and cloned, GFP has become a crucial molecule used as a reporter and tagging tool for studying gene activation and developmental patterns.  Osamu Shimomura, Martin Chalfie and Roger Tsien received the Nobel Prize in Chemistry in 2008 for their work on this remarkable molecule.

Publications

 * Publications by J.W. Hastings

Selected publications:
 * Hastings, J.W. (2007) The Gonyaulax clock at 50: translational control of circadian expression. Cold Spring Harb Symp Quant Biol. 72: 141-144.
 * Hastings, J.W. and Morin, J.G. (2006) Photons for reporting molecular events: green fluorescent protein and four luciferase systems. Methods Biochem Anal. 47: 15-38.
 * Nealson, K.H. and Hastings, J.W. (2006) Quorum sensing on a global scale: massive numbers of bioluminescent bacteria make milky seas. Appl. Env. Microbiol. 72: 2295-2297.
 * Liu, L., Wilson, T. and Hastings, J.W. (2004) Molecular evolution of dinoflagellate luciferases, enzymes with three catalytic domains in a single polypeptide. Proc. Natl. Acad. Sci. USA  101: 16555-16560.
 * Viviani, V.R., Hastings, J.W. and Wilson, T. (2002) Two bioluminescent Diptera: the North American Orfelia fultoni and the Australian Arachnocampa flava. Similar niche, different bioluminescence systems.  Photochem. Photobiol. 75: 22-27.
 * Hastings, J.W. and Wood, K.V. (2001) Luciferases did not all evolve from precursors having similar enzymatic properties. pp.199-210, In, Photobiology 2000 (D. Valenzeno and T. Coohill, eds.) Valdenmar Publ. Co., Overland Park, KS.
 * Hastings, J.W. (2001) Fifty years of fun. J. Biol. Rhythms 16: 5-18.
 * Hastings, J.W. and Greenberg, E.P. (1999) Quorum Sensing: The explanation of a curious phenomenon reveals a common characteristic of bacteria. J. Bacteriol. 181: 2667-2668.
 * Wilson, T. and Hastings, J.W. (1998) Bioluminescence Annu. Rev. Cell Devel. Biol.14: 197-230.
 * Hastings, J. W. (1996) Chemistries and colors of bioluminescent reactions: a review. Gene 173: 5-11.
 * Morse, D., Milos, P.M., Roux, E., and Hastings, J.W. (1989) Circadian regulation of the synthesis of substrate binding protein in the Gonyaulax. bioluminescent system involves translational control. Proc. Natl. Acad. Sci. USA 86:172-176.
 * Nicolas, M-T., Nicolas, G., Johnson, C.H., Bassot, J-M. and Hastings, J.W. (1987) Characterization of the bioluminescent organelles in Gonyaulax polyedra. (dinoflagellates) after fast-freeze freeze fixation and antiluciferase immunogold staining. J. Cell Biol. 105: 723-735.
 * Johnson, C.H. and Hastings, J.W. (1986) The elusive mechanism of the circadian clock. American Scientist 74: 29-36.
 * Hastings, J.W. (1983) Biological diversity, chemical mechanisms and evolutionary origins of bioluminescent systems. J. Molecular Evolution 19: 309-321.
 * Dunlap, J. and Hastings, J.W. (1981) The biological clock in Gonyaulax. controls luciferase activity by regulating turnover. J. Biol. Chem. 256: 10509-10518.
 * Nealson, K.H. and Hastings, J.W. (1979) Bacterial bioluminescence: Its control and ecological significance. Microbiol. Rev. 43: 396-518.
 * McMurry, L. and Hastings, J.W. (1972) Circadian rhythms: mechanism of luciferase activity changes in Gonyaulax. Biol. Bull. 143: 196-206.
 * Fogel, M. and Hastings, J.W. (1972) Bioluminescence: Mechanism and mode of control of scintillon activity. Proc. Nat. Acad. Sci. 69: 690-693.
 * Morin, J.G. and Hastings, J.W. (1971) Energy transfer in a bioluminescent system. J. Cell. Physiol. 77: 313-318.
 * Nealson, K., Platt, T. and Hastings, J.W. (1970) The cellular control of the synthesis and activity of the bacterial luminescent system. J. Bact. 104: 313-322.
 * Wilson, T. and Hastings, J.W. (1970) Chemical and biological aspects of singlet excited molecular oxygen. Photophysiology (A.C. Giese, ed.), Vol. V, pp. 49-95, Acad. Press, NY.
 * Hastings, J.W., Mitchell, G.W., Mattingly, P.H., Blinks, J.R. and Van Leeuwen, M. (1969) Response of aequorin bioluminescence to rapid changes in calcium concentration. Nature 222: 1047-1050.
 * Hastings, J.W. Bioluminescence. (1968) Annu. Rev. Biochem. 37: 597-630.
 * Hastings, J.W. and Gibson, Q.H. (1963) Intermediates in the bioluminescent oxidation of reduced flavin mononucleotide. J. Biol. Chem. 238: 2537-2554.
 * Bode, V.C., DeSa, R.J. and Hastings, J.W. (1963) Daily rhythm in luciferin activity in Gonyaulax polyedra. Science 141: 913-915.
 * DeSa, R.J., Hastings, J.W. and Vatter, A.E. (1963) Luminescent "crystalline" particles: An organized subcellular bioluminescent system. Science 141: 1269-1270.
 * Hastings, J.W. (1959) Unicellular clocks. Ann. Rev. Microbiol. 13: 297-312.
 * Hastings, J.W. and Sweeney, B.M. (1957) The luminescent reaction in extracts of the marine dinoflagellate Gonyaulax polyedra. J. Cell and Comp. Physiol. 49: 209-226.
 * Sweeney, B.M. and Hastings, J.W. (1957) Characteristics of the diurnal rhythm of luminescence in Gonyaulax polyedra. J. Cell. and Comp. Physiol. 49: 115-128.
 * McElroy, W.D., Hastings, J.W., Sonnenfeld, V. and Coulombre, J. (1953) The requirement of riboflavin-phosphate for bacterial luminescence. Science 118: 385-386.
 * Hastings, J.W., McElroy, W.D. and Coulombre, J. (1953) The effect of oxygen upon the immobilization reaction in firefly luminescence. J. Cell and Comp. Physiol. 42: 137-150.
 * Hastings, J.W. (1952) Oxygen concentration and bioluminescence intensity II: Cypridina hilgendorfii. J. Cell. and Comp. Physiol. 40: 1-9.
 * Hastings, J.W. (1952) Oxygen concentration and bioluminescence intensity. I: Bacteria and fungi. J. Cell and Comp. Physiol. 39: 1-30.