John Woodland Hastings
March 24, 1927 |
|Fields||Bioluminescence, Circadian rhythms|
|Alma mater||Johns Hopkins University, 1951-1953 Postdoctoral Fellow with W. D. McElroy|
|Doctoral students||David Johnson States|
|Known for||Founding circadian biology|
|Notable awards||NATO Senior Fellow in Science, Foundation Curie, Orsay, France, 1977|
John Woodland "Woody" Hastings, PhD., born March 24, 1927 in Maryland, is a leader in the field of photobiology, especially bioluminescence, and is one of the founders of the field of circadian biology (the study of circadian rhythms, or the sleep-wake cycle). He is the Paul C. Mangelsdorf Professor of Natural Sciences and Professor 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 fungi, cnidarians, ctenophores, polychaetes, insects (fireflies and dipterans), ostracod crustaceans, millipedes, tunicates, and fishes with bacterial light organs. His laboratory produced the first evidence for quorum sensing in bacteria, early evidence of the molecular mechanisms of circadian clock regulation in organisms (first using dinoflagellate luminescence and then expanded to other cellular proteins), and some of the initial studies of energy transfer in green fluorescent proteins (GFP) in cnidarian luminescence.
Hastings lived in Seaford, Delaware during his early childhood; in 1937, he joined the choir at the Cathedral of Saint John the Divine and attended the choir's in-house boarding school, visiting his family during vacations. Hastings moved to Lenox School in Lenox, Massachusetts in 1941 to complete his secondary education and was interested in literature, physica, mathematics, ice hockey and basketball.
Awards and honors
Throughout his career Hastings has received numerous awards and honors:
- Guggenheim Fellow, 1965;
- Elected to the Johns Hopkins Society of Scholars, 1969;
- Elected to the American Academy of Arts and Sciences, 1972;
- NATO Senior Fellow in Science, Foundation Curie, Orsay, France, 1977;
- Alexander von Humboldt Fellow, Bonn, Germany 1979-80 & 1993;
- Yamada Foundation Fellow, Osaka, Japan, 1986;
- NIMH Merit Award, 1990 &1994;
- Fellow of the American Academy of Microbiology, 2003;
- American Society for Photobiology Lifetime Achievement Award, 2003;
- Elected to the National Academy of Sciences, 2003;
- Recipient of the Farrell Prize in Sleep Medicine for his contributions to and for founding the field of circadian rhythms, 2006.
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 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 Physiology Course there from 1962-.1966, and served as a trustee from 1966-1970.
Luminescent Bacteria: Hastings' investigations of luminous bacteria acted as a catalyst for the 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, and the first evidence for quorum sensing, a form of bacterial communication. In quorum sensing (initially termed autoinduction), the bacteria release a substance into the medium, the autoinducer. Once the concentration of this substance reaches a critical level (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. It is now known that in many pathogenic bacteria, there is delayed production of toxins, which serve to greatly augment their pathogenicity, this is similar to what happens for luciferase proteins. By curtailing their toxin output until the bacterial populations are substantial, these bacteria can generate massive quantities of toxin quickly and thereby swamp the defences of the host.
Luminescent Dinoflagellates: In early 1954 at Northwestern University, Hastings, his students and colleagues studied cellular and molecular aspects of bioluminescence in dinoflagellates [especially Lingulodinium polyedrum (formerly Gonyaulax polyedra)]. They elucidated the structures of the luciferins and luciferases, the organization and regulation of their associated genes, temporal control mechanisms, and the actual sub-cellular 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 the 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 spearheaded 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. 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. 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.
- 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.; 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.; Greenberg, E.P. (1999). "Quorum Sensing: The explanation of a curious phenomenon reveals a common characteristic of bacteria". J. Bacteriol 181: 2667–2668.
- Comolli, J. and Hastings J. W. (1999) Novel Effects on The Gonyaulax Circadian System Produced by the Protein Kinase Inhibitor Staurosporine. J. Biol. Rhythms 14: 10-18.
- 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. doi:10.1016/0378-1119(95)00676-1. PMID 8707056.
- Morse, D.; Milos, P.M.; Roux, E.; 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.; 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.; 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.
- Taylor, W.R.; Dunlap, J.C.; Hastings, J.W. (1982). "Inhibitors of protein synthesis on 80s ribosomes phase shift the Gonyaulax. clock". J. Exp. Biol 97: 121–136.
- Dunlap, J.; Hastings, J.W. (1981). "The biological clock in Gonyaulax. controls luciferase activity by regulating turnover". J. Biol. Chem 256: 10509–10518.
- Nealson, K.H.; 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.; Hastings, J.W. (1972). "Bioluminescence: Mechanism and mode of control of scintillon activity. Proc. Nat. Acad". Sci 69: 690–693.
- Morin, J.G.; 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.; 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.
- Krieger, N.; Hastings, J.W. (1968). "Bioluminescence: pH activity profiles of related luciferase fractions". Science 161: 586–589.
- Hastings, J.W.; 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.; Hastings, J.W. (1963). "Daily rhythm in luciferin activity in Gonyaulax polyedra". Science 141: 913–915.
- DeSa, R.J.; Hastings, J.W.; 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.; 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.; Coulombre, J. (1953). "The requirement of riboflavin-phosphate for bacterial luminescence". Science 118: 385–386.
- Hastings, J.W.; McElroy, W.D.; 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. (1952b). "Oxygen concentration and bioluminescence intensity II: Cypridina hilgendorfii". J. Cell. and Comp. Physiol 40: 1–9.
- Hastings, J.W. (1952a). "Oxygen concentration and bioluminescence intensity. I: Bacteria and fungi". J. Cell and Comp. Physiol 39: 1–30.
- "David J. States". Stateslab.org. Retrieved 2011-06-17.
- "2006 Farrell Prize recipient J. Woodland Hastings | Division of Sleep Medicine @ Harvard". Sleep.med.harvard.edu. Retrieved 2011-06-17.
- "Faculty Profile: J. Woodland Hastings, PhD | Division of Sleep Medicine @ Harvard Medical School". Sleep.med.harvard.edu. Retrieved 2011-06-17.
- Hastings Lab Home page[dead link]
- "Hastings Lab: J. Woodland Hastings". Mcb.harvard.edu. Retrieved 2011-06-17.
- Hastings, J.W. and Greenberg, E.P. (1999)
- Sweeney, B.M. and Hastings, J.W. (1957)
- Hastings, J.W. (2007)
- Morin, J.G. and Hastings, J.W. (1971)
- Hastings, J.W. and Morin, J.G. (2006)
- Davis, Tinsley H. (2007-01-10). "Profile of J. Woodland Hastings". Proc. Natl. Acad. Sci. U.S.A. 104 (3): 693–5. doi:10.1073/pnas.0610519104. PMC 1783375. PMID 17215362.
- Dept of MCB, Harvard U: News and Events - MCB News[dead link]
- Nealson, K., Platt, T. and Hastings, J.W. (1970)
- Hastings, J.W. and Gibson, Q.H. (1963)
- Nealson, K., Platt, T. and Hastings, J.W. (1970),Hastings, J.W. and Greenberg, E.P. (1999)
- Hastings, J.W. and Sweeney, B.M. (1957), Sweeney, B.M. and Hastings, J.W. (1957)
- Fogel, M. and Hastings, J.W. (1972),McMurry, L. and Hastings, J.W. (1972)
- DeSa, R.J., Hastings, J.W. and Vatter, A.E. (1963),Nicolas, M-T., Nicolas, G., Johnson, C.H., Bassot, J-M. and Hastings, J.W. (1987)
- Krieger, N. and Hastings, J.W. (1968)
- Nicolas, M-T., Nicolas, G., Johnson, C.H., Bassot, J-M. and Hastings, J.W. (1987)
- Liu, L., Wilson, T. and Hastings, J.W. (2004)
- Bode, V.C., DeSa, R.J. and Hastings, J.W. (1963),McMurry, L. and Hastings, J.W. (1972)
- Dunlap, J. and Hastings, J.W. (1981)
- Morse, D., Milos, P.M., Roux, E., and Hastings, J.W. (1989),Hastings, J.W. (2007)
- Taylor, W.R., Dunlap, J.C., Hastings, J.W. (1982)
- Comolli, J. and Hastings J. W. (1999)
- Hastings, J.W. (1952a, 1952b)
- Hastings, J.W., McElroy, W.D. and Coulombre, J. (1953)
- McElroy, W.D., Hastings, J.W., Sonnenfeld, V. and Coulombre, J. (1953)
- Hastings' Department of Molecular and Cellular Faculty Page
- Hastings Lab Home Page
- Hastings Page at the Department of Molecular and Cellular Biology at Harvard
- National Academy of Sciences profile of Professor J. Woodland Hastings