Hastings lived in
Seaford, Delaware, during his early childhood; in 1937, he joined the choir at the
Cathedral of St. 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, physics, mathematics,
ice hockey and basketball.[11]
Awards and honors
Throughout his career Hastings received numerous awards and honors:
Recipient of the Farrell Prize in Sleep Medicine for his contributions to and for founding the field of circadian rhythms, 2006.
Career
Hastings began his graduate studies at
Princeton University 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.[12] He then joined the lab of
William D. McElroy, another student of Harvey’s, at
Johns Hopkins University 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.
In 1953 he joined the faculty in the Department of Biological Sciences at
Northwestern University. In 1954 he began a long collaboration with
Beatrice M. Sweeney, who was then at the
Scripps Institution of Oceanography, in elucidating the cellular and biochemical mechanisms of luminescence in the unicellular dinoflagellate Lingulodinium polyedrum (formerly known as Gonyaulax polyedra). A byproduct of this initial research was their discovery of circadian control of the luminescence.
In 1957, Hastings next took a faculty position in the Biochemistry Division of the Chemistry Department at the
University of Illinois at Urbana–Champaign where he continued his focus on dinoflagellate and bacterial luminescence and dinoflagellate circadian rhythms. Hastings joined the faculty of
Harvard University as Professor of Biology in 1966. 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[11] and received the Farrell Prize in Sleep Medicine for his work on circadian rhythms in 2006.[2][13]
For over 50 years he also had an affiliation with the
Marine Biological Laboratory in Woods Hole, Massachusetts. He was the director of the
Physiology Course there from 1962 to 1966, and served as a trustee from 1966 to 1970.
Luminescent Bacteria: Hastings' investigations of luminous bacteria acted as a catalyst for the discoveries of the biochemical mechanisms involved in their light production,[14] the discovery of a flavin to be a substrate in its
luciferase reaction,[15] the determination of
gene regulation of the luciferases, and the first evidence for
quorum sensing,[16] 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,[17] the organization and regulation of their associated genes, temporal control mechanisms,[18] and the actual sub-cellular identity and location of the light emitting elements, which they termed
scintillons.[19] 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.[20] 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.[21] More recently, the lab 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."[22] 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 spearheaded our understanding of the molecular mechanisms involved in control of circadian rhythms,[23] 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.[24] 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.[25] 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.[26] At still another level,
protein phosphorylation inhibitors also influence the period of the rhythm.[27]
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.[28] This work showed that oxygen gating is the mechanism for firefly flashing.[29] 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.[30] 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).[9] Once characterized and cloned, GFP has become a crucial molecule used as a reporter and tagging tool for studying gene activation and developmental patterns.[10]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.; Morin, J.G. (2006). "Photons for reporting molecular events: green fluorescent protein and four luciferase systems". Methods Biochem Anal. Methods of Biochemical Analysis. 47: 15–38.
doi:
10.1002/0471739499.ch2.
ISBN9780471739494.
PMID16335708.
Viviani, V.R.; Hastings, J.W.; Wilson, T. (2002). "Two bioluminescent Diptera: the North American Orfelia fultoni and the Australian Arachnocampa flava. Similar niche, different bioluminescence systems". Photochem. Photobiol. 75 (1): 22–27.
doi:
10.1562/0031-8655(2002)075<0022:tbdtna>2.0.co;2.
PMID11837324.
S2CID198153893.
Okamoto, OK; Liu, L; Robertson, DL; Hastings, JW (December 2001). "Members of a dinoflagellate luciferase gene family differ in synonymous substitution rates". Biochemistry. 40 (51): 15862–8.
doi:
10.1021/bi011651q.
PMID11747464.
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.
Comolli, J.; Hastings, J. W. (1999). "Novel Effects on The Gonyaulax Circadian System Produced by the Protein Kinase Inhibitor Staurosporine". J. Biol. Rhythms. 14 (1): 10–18.
doi:
10.1177/074873099129000399.
PMID10036988.
S2CID16522583.
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 (5198): 1047–1050.
Bibcode:
1969Natur.222.1047H.
doi:
10.1038/2221047a0.
PMID4389183.
S2CID4182048.
Hastings, J.W.; Sweeney, B.M. (1957). "The luminescent reaction in extracts of the marine dinoflagellate Gonyaulax polyedra". J. Cell. Comp. Physiol. 49 (2): 209–226.
doi:
10.1002/jcp.1030490205.
PMID13481063.
Sweeney, B.M.; Hastings, J.W. (1957). "Characteristics of the diurnal rhythm of luminescence in Gonyaulax polyedra". J. Cell. Comp. Physiol. 49: 115–128.
doi:
10.1002/jcp.1030490107.
Hastings, J.W.; McElroy, W.D.; Coulombre, J. (1953). "The effect of oxygen upon the immobilization reaction in firefly luminescence". J. Cell. Comp. Physiol. 42 (1): 137–150.
doi:
10.1002/jcp.1030420109.
PMID13084711.