| 词条 | Amita Sehgal |
| 释义 |
| honorific_prefix = | name = Amita Sehgal | honorific_suffix = | native_name = | native_name_lang = | image = | image_size = | image_upright = | alt = | caption = | death_date = | death_place = | death_cause = | resting_place = | resting_place_coordinates = | other_names = | pronounce = | residence = | citizenship = | nationality = | fields = chronobiology | workplaces = Perelman School of Medicine | patrons = | education = | alma_mater = Delhi University, Jawaharlal Nehru University, Cornell University | thesis_title = | thesis_url = | thesis_year = | doctoral_advisor = | academic_advisors = Michael Young | doctoral_students = | notable_students = | known_for = | influences = | influenced = | awards = | author_abbrev_bot = | author_abbrev_zoo = | spouse = | partner = | children = | signature = | signature_alt = | website = | footnotes = }}Amita Sehgal is a molecular biologist and chronobiologist in the Department of Neuroscience at the Perelman School of Medicine at the University of Pennsylvania.[1] Sehgal has been involved in the discovery of Drosophila TIM and many other important components of the Drosophila clock mechanism.[2] Sehgal has contributed greatly to the development of Drosophila as a model for the study of sleep.[3][4] Her research continues to be focused on understanding the genetic basis of sleep and also how circadian systems relate to other aspects of physiology.[1] Education and early careerDr. Sehgal grew up in India, and earned her BSc as an undergraduate at Delhi University and her MSc at Jawaharlal Nehru University, both in New Delhi, India.[5] After earning her master's degree, she worked in a lab studying the DNA repair process in Muscular Dystrophy.[5] She began pursuing her PhD in cell biology and genetics at Cornell University in 1983.[5] It was here, while studying a human neuronal growth factor, that her interest in science truly developed.[5] In 1988, she began her Postdoctoral Fellowship at Rockefeller University in the lab of Michael Young, where she had her first exposure to the study of circadian rhythms, a field in which she has since remained.[5] ResearchTimeline of selected major research contributions
Timeless and PeriodAmita Sehgal has contributed tremendously towards the understanding of the biological clock of Drosophila melanogaster[6] In 1994, Sehgal, Price, Man, and Young, through forward genetics, discovered a mutant of the gene timeless (TIM) in Drosophila melanogaster.[2] In the following year, Sehgal et al. cloned TIM through positional cloning and were able to show that TIM and PER had similar cycling levels of their mRNA and protein.[2] A yeast 2-hybrid then showed that TIM protein binds directly to PER. PER and TIM dimerize and accumulate during the day. In the evening, they enter the nucleus to inhibit the transcription of their mRNA. Phosphorylation of PER and TIM then leads to their degradation.[2] In 1996, Sehgal was involved in an experiment that showed degradation in TIM levels caused by a pulse of light that resets the molecular clock.[2] Sehgal and her team later showed dCRY is responsible for the degradation of TIM.[2] Neurofibromin 1Neurofibromin 1 (NF1) is a tumor suppressor gene known to be dis-regulated in Neurofibromatosis type 1, a disorder which causes tumors along the spine. In 2001, Sehgal and her colleagues learned that some patients with Neurofibromatosis type 1 also experience irregularities in their sleep, and so decided to investigate the circadian rhythms of flies with a nonfunctional NF1 gene.[7] They found that these flies also have disrupted circadian rhythms, and these rhythms could be restored by inserting NF1 transgenes, thus proving that NF1 is involved in the circadian pathway.[7] They showed that in flies, NF1 functions through the MAP kinase pathway, which is the same pathway implicated in Neurofibromatosis type 1 in humans.[7]JetlagIn 2006, Sehgal and her colleagues discovered a mutant fly which takes an abnormally long time to adjust to new light-dark cycles.[20] They named the underlying mutated gene jetlag (jet).[20] This gene codes for an F-box protein called JET, a ubiquitin ligase that facilitates resetting the drosophila clock.[20] Sequencing of the gene revealed two alleles of jetlag: the "c" allele (common) and the "r" allele (rare).[20] In the presence of CRYPTOCHROME (CRY), JET plays a major role in the degradation of TIMELESS (TIM) protein in response to light, which is necessary for the clock to entrain to external light cues.[8] Mushroom bodiesMushroom bodies are located in the brains of Drosophila and are known to play a role in learning, memory, olfaction, and locomotion.[9] In 2006, Sehgal and her colleagues discovered that mushroom bodies also play a major role in regulating sleep in flies.[9][10] By using a steroid called RU-486 (Mifepristone) to regulate protein kinase A (PKA), they were able to upregulate and downregulate the expression of genes in specific areas like the mushroom bodies, and found that this structure is critical for fly sleep.[11] While the specific pathway through which these mushroom bodies regulate sleep is currently unknown, it may be that they are involved in inhibiting processing of sensory information, allowing flies to fall asleep.[11]SleeplessIn 2008, Sehgal et al. discovered the sleepless gene in fruit flies through insertional mutagenesis.[12] Mutations in the sleepless gene caused the flies to sleep 80% less than normal flies[13] and live half as long as normal flies.[14] Sehgal et al. observed flies had extreme loss of sleep when the flies completely lacked the SLEEPLESS protein. Flies with mutations which lowered the level of SLEEPLESS protein had normal levels of sleep, but when the flies were sleep-deprived, they showed abnormal recovery sleep.[13] Sehgal et al. also found increased stem cell activity within the testes of male flies with mutations in sleepless.[14] The SLEEPLESS protein activates Shaker potassium channels and inhibits nicotinic acetylcholine receptors.[15] GABATShortly after discovering the sss gene, Sehgal and colleagues used an unbiased proteomic approach and compared brain proteins between sss mutants and wild type flies.[16] They discovered that levels of a mitochondrial γ-aminobutyric acid transaminase (GABAT) are increased in sss mutant brains. sleepless mutants also have low GABA levels. Flies with GABAT mutations showed prolonged sleep time and more solid sleep. Loss of GABAT completely reversed the short sleep phenotype of the sss mutants and restores the sleep of the latter. Sehgal et al. also found GABAT is required in glia to promote wakefulness in response to loss of sleepless in a distinct set of surrounding neurons. "The findings shed light on mechanisms that may be shared between sleep disruption and some neurological disorders",[17] such as epilepsy. RedeyeSehgal's lab recently identified a new gene involved in the regulation of sleep in fruit flies, redeye. The redeye gene was discovered through random mutation of the fruit fly chromosome 3. Sehgal found the longer a fly is awake, the higher the level of redeye becomes in the fly.[14] Redeye levels showed changes throughout the day even when the genes which are part of the circadian clock were mutated.[14] This observation indicates redeye is controlled by factors outside of the circadian clock.[14] Awards and positionsPositions[3][18]
Awards[5]
References1. ^1 {{Cite web|title = Circadian Rhythms and Sleep|url = http://www.hhmi.org/research/circadian-rhythms-and-sleep|accessdate = 2015-04-09|website = Howard Hughes Medical Institute|date = May 2012}} {{Authority control}}{{DEFAULTSORT:Sehgal, Amita}}2. ^1 2 3 4 5 {{Cite journal|title = Circadian rhythms from flies to human|url = http://www.nature.com/nature/journal/v417/n6886/full/417329a.html|journal = Nature|date = May 16, 2002|access-date = 2015-04-09|issn = 0028-0836|pages = 329–335|volume = 417|issue = 6886|doi = 10.1038/417329a|first = Satchidananda|last = Panda|first2 = John B.|last2 = Hogenesch|first3 = Steve A.|last3 = Kay|pmid=12015613|bibcode = 2002Natur.417..329P}} 3. ^1 {{Cite web|url = http://store.elsevier.com/Amita-Sehgal/ELS_1184064/|title = Amita Sehgal|date = |accessdate = |website = |last = |first = }} 4. ^{{Cite journal|url = http://www.sciencedirect.com/science/article/pii/S1044743196900135|title = Control of Circadian Rhythms by a Two-Component Clock|last = Sehgal|first = Amita|date = April 19, 2002|journal = Molecular and Cellular Neuroscience|doi = 10.1006/mcne.1996.0013|pmid = 8726101|access-date = April 23, 2015|last2 = Ousley|first2 = Andrea|last3 = Hunter-Ensor|first3 = Melissa|volume=7|issue = 3|pages=165–172}} 5. ^1 2 3 4 5 {{Cite web|url = http://www.hhmi.org/scientists/amita-sehgal|title = Amita Sehgal, PhD|date = |accessdate = March 31, 2015|website = Howard Hughes Medical Institute|last = |first = }} 6. ^{{Cite web|url = http://www.hhmi.org/news/experiments-illuminate-workings-biological-clocks|title = Experiments Illuminate Workings of Biological Clocks|date = |accessdate = 2015-04-21|website = Howard Hughes Medical Institute|last = |first = }} 7. ^1 2 {{Cite web|url = http://www.hhmi.org/news/new-pathway-understanding-circadian-rhythms|title = New Pathway to Understanding Circadian Rhythms|date = September 21, 2001|accessdate = April 23, 2015|website = Howard Hughes Medical Institute|last = |first = }} 8. ^1 2 3 4 {{Cite journal|url = http://www.pnas.org/content/103/47/17583.full|title = Timeless Genes and Jetlag|last = Van Gelder|first = Russell|date = November 21, 2006|journal = PNAS|doi = 10.1073/pnas.0608751103|pmid = 17101961|access-date = April 22, 2015|pmc=1693787|volume=103|issue = 47|pages=17583–4|bibcode = 2006PNAS..10317583V}} 9. ^1 {{Cite journal|title = Molecular Architecture of Smell and Taste in Drosophila|last = Vosshall|first = Leslie B.|date = July 2007|journal = Annual Review of Neuroscience|doi = 10.1146/annurev.neuro.30.051606.094306|pmid = 17506643|last2 = Stocker|first2 = Reinhard F.|volume=30|pages=505–533}} 10. ^{{Cite journal|title = Circadian Organization of Behavior and Physiology in Drosophila|last = Allada|first = Ravi|date = November 13, 2009|journal = Annual Review of Physiology|doi = 10.1146/annurev-physiol-021909-135815|pmid = 20148690|last2 = Chung|first2 = Brian Y.|pmc=2887282|volume=72|pages=605–24}} 11. ^1 {{Cite web|url = http://www.hhmi.org/news/researchers-find-snooze-button|title = Researchers Find the Snooze Button|date = June 8, 2006|accessdate = April 23, 2015|website = Howard Hughes Medical Institute News|last = |first = }} 12. ^{{Cite journal|title = The genetic and molecular regulation of sleep: from fruit flies to humans|journal = Nature Reviews Neuroscience|date = August 2009|issn = 1471-003X|pmc = 2767184|pmid = 19617891|pages = 549–560|volume = 10|issue = 8|doi = 10.1038/nrn2683|first = Chiara|last = Cirelli}} 13. ^1 {{Cite web|title = Research News: Fruit Fly Study Yields a Gene Required for Peaceful Slumber {{!}} Howard Hughes Medical Institute (HHMI)|url = http://www.hhmi.org/news/fruit-fly-study-yields-gene-required-peaceful-slumber|accessdate = 2015-04-09}} 14. ^1 2 3 4 {{Cite web|title = HHMI Bulletin Spring 2014: Around the Clock {{!}} Howard Hughes Medical Institute (HHMI)|url = http://www.hhmi.org/bulletin/spring-2014/around-clock|accessdate = 2015-04-09}} 15. ^{{Cite journal|title = SLEEPLESS is a bifunctional regulator of excitability and cholinergic synaptic transmission|journal = Current Biology|date = Mar 17, 2014|issn = 1879-0445|pmc = 4059605|pmid = 24613312|pages = 621–629|volume = 24|issue = 6|doi = 10.1016/j.cub.2014.02.026|first = Meilin|last = Wu|first2 = James E.|last2 = Robinson|first3 = William J.|last3 = Joiner}} 16. ^{{Cite journal|last=Chen|first=W-F|last2=Maguire|first2=S|last3=Sowcik|first3=M|last4=Luo|first4=W|last5=Koh|first5=K|last6=Sehgal|first6=A|title=A neuron–glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants|journal=Molecular Psychiatry|volume=20|issue=2|pages=240–251|doi=10.1038/mp.2014.11|pmc=4168011|pmid=24637426|year=2015}} 17. ^{{Cite web|url=https://www.sciencedaily.com/releases/2014/04/140401142127.htm|title=www.sciencedaily.com/releases/2014/04/140401142127.htm|website=www.sciencedaily.com|access-date=2016-05-09}} 18. ^{{Cite web|url=http://www.upenn.edu/pennnews/current/peopleofpenn/amita-sehgal |title=Amita Sehgal |date= |accessdate=April 8, 2015 |website=Penn Current |last= |first= |editor-last=Johnson |editor-first=Greg |deadurl=yes |archiveurl=https://web.archive.org/web/20150908083239/http://www.upenn.edu/pennnews/current/peopleofpenn/amita-sehgal |archivedate=September 8, 2015 }} 19. ^{{citation|url=http://www.nasonline.org/news-and-multimedia/news/may-3-2016-NAS-Election.html|title=National Academy of Sciences Members and Foreign Associates Elected|department=News from the National Academy of Sciences|publisher=National Academy of Sciences|date=May 3, 2016|accessdate=2016-05-14}}. 12 : Cornell University alumni|Jawaharlal Nehru University alumni|Living people|Indian molecular biologists|Perelman School of Medicine at the University of Pennsylvania|University of Delhi alumni|Indian women molecular biologists|Year of birth missing (living people)|Place of birth missing (living people)|Chronobiologists|Members of the United States National Academy of Sciences|Women scientists from Delhi |
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