31 - Frontiers in the effects of light on circadian rhythms
Florida 1 08:00 - 10:00
|Chair(s): Mary Harrington|
09:00 Light Effects on the Human Circadian Timing System JF Duffy*, Harvard Medical School and Brigham and Women's Hospital
; ED Chinoy, Harvard Medical School and Brigham and Women's Hospital; KM Zitting, Harvard Medical School and Brigham and Women's Hospital
Abstract: Nearly all organisms possess a biological timing system that produces rhythms in physiology and behavior with a ~24-hour cycle length. These near-24-h circadian rhythms are synchronized to the 24-h day by signals from the environment, and in humans this is primarily achieved by exposure to light and darkness. As a diurnal species, adult humans whose circadian system is synchronized with their environment will be alert during the day and able to sleep for an extended time during the night. The consequences of not being entrained are experienced by those such as shift workers who must remain awake at night to work and then attempt to sleep during the day, and by individuals who have recently traveled across multiple time zones. Light exposure has phase-dependent effects on circadian rhythms, with the magnitude and direction of alterations in rhythm timing dependent on the biological time at which the light exposure occurred. Other features including wavelength, illuminance, duration, and pattern of exposure also impact the circadian response to light. Thus, light exposure at some times of day will produce shifts in circadian rhythm timing to earlier hours, light at other times of day will produces shifts to later hours, and there are times at which the same duration, wavelength, and intensity of light will produce almost no change in circadian rhythm timing. In addition to the entraining and phase-shifting effects that light produces on human circadian rhythms, there are also direct effects, including suppression of the hormone melatonin and increases in alertness. With understanding of the direct and indirect light effects on the human circadian system, researchers have used that information to design therapies to improve on-shift alertness and off-shift sleep in night workers, to more quickly adjust the biological clocks of travelers, and to shift sleep timing in individuals with circadian rhythm sleep disorders.
09:30 Circadian Clock, UV-DNA Repair and Skin: Implications in Skin Carcinogenesis and Sunburn Erythema S Gaddameedhi*, Washington State University
Abstract: Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn as a result of exposure to excessive UV light and damage to DNA confer an increased risk for melanoma and non-melanoma skin cancer. Previous reports have shown that both nucleotide excision repair, which is the sole pathway for removing UV-induced DNA photoproducts, and DNA replication, are regulated by the circadian clock in mouse skin. Furthermore, the timing of UV exposure during the circadian cycle has been shown to affect skin carcinogenesis in mice, with up to a 5-fold difference in invasive carcinoma. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, we observed that sunburn apoptosis, inflammatory cytokine induction, and erythema peaked at 3-fold following an acute early morning exposure to UV when compared to following an afternoon/evening exposure. Furthermore, the circadian rhythmicity of these responses was found to be correlated with activation of ATR-mediated DNA damage checkpoint signaling and p53 activity, which is known to control the process of sunburn apoptosis. These data provide the first evidence that the circadian clock plays an important role in skin carcinogenesis and the erythemal response in UV-irradiated mouse skin. Since mice are nocturnal and humans are diurnal, we expect the circadian clock outputs of the two organisms to exhibit opposite phases. On this basis it would be expected that humans may be less prone to UV-induced skin toxicity in the morning and more prone in the evening. While presenting the above findings on mouse models, this presentation will highlight the potential application of the circadian clock that modulate the skin responses to DNA damaging mediated therapeutics that are commonly used in the field of dermatology.
10:00 Using light to tell time RJ Lucas*, University of Manchester
Abstract: A master circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) orchestrates twenty-four hour rhythms in mammalian physiology and behaviour. The SCN clock is reset to local time primarily by a projection from the retina that conveys information about the diurnal light dark cycle. The conventional view of this sensory pathway is that it efficiently extracts information about background light intensity (irradiance) as the most reliable indicator of time of day. We have been studying the visual information reaching the SCN in the mouse and show that neurones in the mouse SCN also respond to changes in colour and according to spatial patterns. The former provides an additional time of day cue that is used to set the phase of circadian clocks. The appearance of information about spatial patterns in the SCN has less obvious relevance for telling time of day, but may rather relate to the SCN's other function as a control centre behavioural and physiological state.
10:30 Mammalian Period Performs Both Repressor and Activator Functions by Displacing the CLOCK-BMAL1 Activator Complex in a Cryptochrome-Dependent Manner YY Chiou*, UNC Chapel Hill
; Y Yang, UNC Chapel Hill; N Rashid, UNC Chapel Hill; R Ye, UNC Chapel Hill; CP Selby, UNC Chapel Hill; A Sancar, UNC Chapel Hill
Abstract: The mammalian circadian clock is based on a transcription-translation feedback loop (TTFL) consolidated by secondary loops. In the primary TTFL, the CLOCK-BMAL1 heterodimer acts as the transcriptional activator, and Cryptochrome (CRY) and Period (PER) proteins function as repressors. PER represses by displacing CLOCK-BMAL1 from promoters in a CRY-dependent manner. Interestingly, genes with complex promoters may either be repressed or activated by PER, depending on the particular promoter regulatory elements. Here, using mouse cell lines with defined mutations in clock genes, and RNA and ChIP-seq analyses, we elucidate the dual functions of PER as activator and repressor in a context-dependent manner.