Charles Weitz
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Charles Weitz
Charles J. Weitz is a chronobiologist and neurobiologist whose work primarily focuses on studying the molecular biology and genetics of circadian clocks. At Harvard University, the Weitz lab consolidated understanding towards the transcriptional architecture of the circadian clock in ''Drosophila'' and mice models. He determined the role of the CLOCK protein, which serves to activate transcription of circadian clock genes. The Weitz lab is also accredited for discovering direct transcription termination by the PER complex, which regulates the expression of genes involved in producing the circadian rhythm. Currently, Weitz's work focuses on using cryo-electron microscopy to study endogenous circadian protein complexes. Education and academic career Education Charles J. Weitz earned his undergraduate degree in Philosophy from Harvard University in 1978. He received his medical degree from the Stanford University School of Medicine in 1983. After medical school, he completed ...
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Chronobiology
Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος (''chrónos'', meaning "time"), and biology, which pertains to the study, or science, of life. The related terms ''chronomics'' and ''chronome'' have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required. Chronobiological studies include but are not limited to comparative anatomy, physiology, genetics, molecular biology and behavior of organisms related to their biological rhythms. Other aspects include epigenetics, development, reproduction, ecology and evolution. The subject Chronobiology studies variations of t ...
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Clock
A clock or chronometer is a device that measures and displays time. The clock is one of the oldest Invention, human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month, and the year. Devices operating on several physical processes have been used over the Millennium, millennia. Some predecessors to the modern clock may be considered "clocks" that are based on movement in nature: A sundial shows the time by displaying the position of a shadow on a flat surface. There is a range of duration timers, a well-known example being the hourglass. Water clocks, along with sundials, are possibly the oldest time-measuring instruments. A major advance occurred with the invention of the verge escapement, which made possible the first mechanical clocks around 1300 in Europe, which kept time with oscillating timekeepers like balance wheels., pp. 103–104., p. 31. Traditionally, in horology (the study of timekeeping), the ...
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Transcription Translation Feedback Loop
Transcription-translation feedback loop (TTFL) is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products. Discovery Circadian rhythms have been documented for centuries. For example, French astronomer Jean-Jacques d’Ortous de Mairan noted the periodic 24-hour movement of ''Mimosa'' plant leaves as early as 1729. However, science has only recently begun to uncover the cellular mechanisms responsible for driving observed circadian rhythms. The cellular basis of circadian rhythms is supported by the fact that rhythms have been observed in single-celled organisms Beginning in the 1970s, experiments conducted by Ron Konopka and colleagues, in which forward genetic methods were used to induce mutation, revealed that ''Drosophila melanogaster'' specimens with altered ''period'' (''Per'') genes also demonstrated altered ...
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CLOCK/BMAL1
Basic helix-loop-helix ARNT-like protein 1 or aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), or brain and muscle ARNT-like 1 is a protein that in humans is encoded by the ''BMAL1'' gene on chromosome 11, region p15.3. It's also known as ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''BMAL1'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''BMAL1'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The BMAL1 protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''BMAL1'' is the only clock gene without which the circadian clock fails to function in humans. ''BMAL1'' has also been identified as a candidate gene for susc ...
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PER1
Period circadian protein homolog 1 is a protein in humans that is encoded by the ''PER1'' gene. Function The PER1 protein is important to the maintenance of circadian rhythms in cells, and may also play a role in the development of cancer. This gene is a member of the Period (gene), period family of genes. It is expressed with a daily oscillating circadian rhythm, or an oscillation that cycles with a period of approximately 24 hours. PER1 is most notably expressed in the region of the brain called the suprachiasmatic nucleus (SCN), which is the primary circadian pacemaker in the mammalian brain. PER1 is also expressed throughout mammalian peripheral tissues. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression of PER1 in the suprachiasmatic nucleus will free-run in constant darkness, meaning that the 24-hour period of the cycle will persist without the aid of external light cues. Subsequently, a shi ...
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Negative Feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. Whereas positive feedback tends to instability via exponential growth, oscillation or chaos theory, chaotic behavior, negative feedback generally promotes stability. Negative feedback tends to promote a settling to List of types of equilibrium, equilibrium, and reduces the effects of perturbations. Negative feedback loops in which just the right amount of correction is applied with optimum timing, can be very stable, accurate, and responsive. Negative feedback is widely used in Mechanical engineering, mechanical and electronic engineering, and it is observed in many other fields including biology, chemistry and economics. General negative feedback systems are studied in Control engin ...
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Photoreceptor Protein
Photoreceptor proteins are light-sensitive proteins involved in the sensing and response to light in a variety of organisms. Some examples are rhodopsin in the photoreceptor cells of the vertebrate retina, phytochrome in plants, and bacteriorhodopsin and bacteriophytochromes in some bacteria. They mediate light responses as varied as visual perception, phototropism and phototaxis, as well as responses to light-dark cycles such as circadian rhythm and other photoperiodisms including control of flowering times in plants and mating seasons in animals. Structure Photoreceptor proteins typically consist of a protein attached to a non-protein chromophore (sometimes referred as photopigment, even so photopigment may also refer to the photoreceptor as a whole). The chromophore reacts to light via photoisomerization or photoreduction, thus initiating a change of the receptor protein which triggers a signal transduction cascade. Chromophores found in photoreceptors include retinal ( ...
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Cryptochrome
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the '' chromatic'' nature of the photoreceptor, and the '' cryptogamic'' organisms on which many blue-light studies were carried out. The genes ''CRY1'' and ''CRY2'' encode the proteins CRY1 and CRY2, respectively. Cryptochromes are classified into plant Cry and animal Cry. Animal Cry can be further categorized into insect type (Type I) and mammal-like (Type II). CRY1 is a circadian photoreceptor whereas CRY2 is a clock repressor which represses Clock/Cycle (Bmal1) complex in insects and vertebrates. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known ...
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Protein Dimer
In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", ''wikt:di-#Prefix, di-'' + ''wikt:-mer#Suffix, -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins while a protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein IKBKG, NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein- ...
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Negative Feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. Whereas positive feedback tends to instability via exponential growth, oscillation or chaos theory, chaotic behavior, negative feedback generally promotes stability. Negative feedback tends to promote a settling to List of types of equilibrium, equilibrium, and reduces the effects of perturbations. Negative feedback loops in which just the right amount of correction is applied with optimum timing, can be very stable, accurate, and responsive. Negative feedback is widely used in Mechanical engineering, mechanical and electronic engineering, and it is observed in many other fields including biology, chemistry and economics. General negative feedback systems are studied in Control engin ...
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BMAL1
Basic helix-loop-helix ARNT-like protein 1 or aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), or brain and muscle ARNT-like 1 is a protein that in humans is encoded by the ''BMAL1'' gene on chromosome 11, region p15.3. It's also known as ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''BMAL1'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''BMAL1'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The BMAL1 protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''BMAL1'' is the only clock gene without which the circadian clock fails to function in humans. ''BMAL1'' has also been identified as a candidate gene for susc ...
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E-box
An E-box (enhancer box) is a Response element, DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNTG (where N can be any nucleotide), with a palindromic canonical sequence of CACGTG, is recognized and bound by transcription factors to initiate gene transcription (genetics), transcription. Once the transcription factors bind to the promoters through the E-box, other enzymes can bind to the promoter and facilitate transcription from DNA to mRNA. Discovery The E-box was discovered in a collaboration between Susumu Tonegawa's and Walter Gilbert's laboratories in 1985 as a control element in immunoglobulin heavy-chain enhancer. They found that a region of 140 base pairs in the tissue-specific transcriptional enhancer element was sufficient for different levels of transcription Enhancer (genetics), enhancement in different tissues and sequenc ...
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