标题: 2017 Nobel Prize in Medicine: Biological Clock That Underpins Circadian Rhythm [打印本页] 作者: choi 时间: 10-3-2017 15:26 标题: 2017 Nobel Prize in Medicine: Biological Clock That Underpins Circadian Rhythm (1) Press Release. Oct 2, 2017. https://www.nobelprize.org/nobel ... tes/2017/press.html
Note:
(a) "During the 18th century, the astronomer Jean Jacques d'Ortous de Mairan [1678 – 1771; surname: de Mairan] studied mimosa plants, and found that the leaves opened towards the sun during daytime and closed at dusk."
Mimosa 含羞草屬 https://en.wikipedia.org/wiki/Mimosa
(a genus; name meaning)
(b) "During the 1970's, Seymour Benzer and his student Ronald Konopka asked whether it would be possible to identify genes that control the circadian rhythm in fruit flies. They demonstrated that mutations in an unknown gene disrupted the circadian clock of flies."
"Advanced Information" in the left column explains:
In 1971 "Seymour Benzer and his student Ronald Konopka, working at the California Institute of Technology, embarked on studies to identify mutant fruit flies with altered circadian phenotypes. Unlike several geneticists and behavioral scientists of the time, Benzer firmly believed that specific behaviors may be influenced by the action of single genes and that it would be possible to demonstrate this by isolating organisms with altered behavior carrying mutations in individual genes. Using a classical chemical-based mutagenesis strategy [using chemical to create mutations randomly], Benzer and Konopka isolated three different strains of mutant flies showing alterations in the normal 24h cycle of pupal eclosion and locomotor activity (Konopka and Benzer, 1971). One mutant was arrhythmic, another had a shorter period of 19h, and a third had a longer period of 28h. Mapping experiments, using the genetic markers known at the time, roughly localized all three mutants to the same region of the X chromosome of the fruit fly. Importantly, complementation tests suggested that the three mutations involved the same gene, later named period. Based on this, Benzer and Konopka presciently predicted that the arrhythmic mutant would carry a nonsense mutation [which make synthesis of the particular protein prematurely halted, with the half-baked product, being non-functional, was immediately and completely degraded] that inactivated the gene, and that the mutants with longer and shorter periods would carry missense mutations that somehow altered the function of the gene product in opposite ways. Later work [by others, Benzer having moved on to other topics] showed both predictions to be correct."
(c) In Fig 2A, DNA is a double helix, mRNA a bended line segment, and protein a tangle of wool.
(d) "Michael Young identified yet another gene, doubletime, encoding the DBT protein that delayed the accumulation of the PER protein. This provided insight into how an oscillation is adjusted to more closely match a 24-hour cycle."
(i) As you might have already guessed, a gene is identified by lower-case name, and a protein by upper-case one. The same applies to the (three-letter) short form (as in dbt and DBT).
(ii) Advanced Information: "the discovery by Young of the doubletime gene, encoding a kinase DOUBLETIME (DBT) that phosphorylates PER and increases its degradation (Price et al, 1998 [from Young's lab] )."
By definition, a kinase adds a phosphate to another protein -- called phosphorylation in biology. Depending on proteins, phosphorylation causes different outcomes.
(e) All cells in an organism has a biological clock. A title from the Web: "Every Single Cell in Your Body Is Controlled by Its Own Circadian Clock"
(i) Circadian Rhythms Fact Sheet. National Institute of General Medical Sciences (NIGMS), undated https://www.nigms.nih.gov/educat ... rcadianRhythms.aspx
("A master clock in the brain coordinates [some use the verb 'synchronize'] all the biological clocks in a living thing, keeping the clocks in sync. In vertebrate animals, including humans, the master clock is a group of about 20,000 nerve cells (neurons) that form a structure called the suprachiasmatic nucleus, or SCN. The SCN is located in a part of the brain called the hypothalamus and receives direct input from the eyes [specifically retina]")
(i) When you move to another time zone and settle there, light (blue light works the best) resets the master clock in SCN -- a process that takes a couple of days.