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55-555: Steve A. Kay FRS is a British-born chronobiologist who mainly works in the United States . Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014, Steve Kay celebrated 25 years of successful chronobiology research at the Kaylab 25 Symposium, joined by over one hundred researchers with whom he had collaborated with or mentored. Dr. Kay,

110-441: A cryptochrome mutant in fruit flies, also demonstrating that clock genes were distributed all over the body, which was named one of Science's top 10 breakthroughs in 1997. Kay also teamed up with Joe Takahashi to identify fly's CLOCK gene and its binding partner dBMAL1 and complete the transcription-translation feedback loop in flies in 1998. In 1999, Kay established his second lab adjacent to Scripps Research Institute at

165-735: A Chair (all of whom are Fellows of the Royal Society ). Members of the 10 Sectional Committees change every three years to mitigate in-group bias . Each Sectional Committee covers different specialist areas including: New Fellows are admitted to the Society at a formal admissions day ceremony held annually in July, when they sign the Charter Book and the Obligation which reads: "We who have hereunto subscribed, do hereby promise, that we will endeavour to promote

220-528: A circadian clock. Transcription for circadianly regulated mRNA shows regular peaks in morning and evening, which then has implications for the regulation of drug targets. In 2004 Hogenesch left California to become a professor and the Director of Genome Technology at The Scripps Research Institute's other location in West Palm Beach, FL , where he continued his work on transcriptomes. Hogenesch contributed to

275-518: A circadian regulator. Hogenesch has also contributed to the identification of hundreds more genes that modulate circadian rhythms in humans by using genome wide RNAi scanning. More recently, he discovered new clock gene CHRONO using novel computer based machine learning techniques to prioritize clock gene candidates. Hogenesch has also contributed to the field by mentored scientists like Satchin Panda and has collaborated with over 25 other scientists on

330-782: A member of the National Academy of Sciences , U.S.A., briefly served as president of The Scripps Research Institute . and is currently a professor at the University of Southern California . He also served on the Life Sciences jury for the Infosys Prize in 2011. Steve A. Kay was raised on the Isle of Jersey off the coast of Normandy . As a young child, he was fascinated by marine creatures exposed during low tide on Jersey island. His interest in biology deepened when an elementary teacher brought

385-427: A microscope from mainland England into his small classroom. He spent hours looking through the microscope at swimming critters in pond water, amazed by "what was in pond water, or what the edges of a torn piece of paper looked like." By his early teens, Steve Kay knew that biology would be his lifelong passion and aimed to get a PhD. Years later, when his mother died of a progressive motor neuron disease in 2006, Steve Kay

440-632: A professor and the Dean of Dornsife College of Letters, Arts and Sciences at the University of Southern California ( USC ). In September 2015, he was named president of The Scripps Research Institute . In 2016, he was re-appointed to the University of Southern California ( USC ). In 1985, Kay and his colleagues found that the Cab gene was under circadian control in wheat and transgenic tobacco plants during his postdoctoral research. In 1991, Kay extended this research into

495-541: A small molecule, KL001 , that interacts with cryptochrome to prevent ubiquitin -dependent degradation, which results in a longer circadian period. KL001 -mediated cryptochrome stabilization (of both CRY1 and CRY2) was found to restrain glucagon -activated gluconeogenesis . These findings bear the potential to aid in the development of circadian-based diabetic therapeutics. Circadian clocks have also been shown to influence cancer treatments, where circadian disruption accelerates processes and drug responses are affected by

550-508: A study manipulating the ubiquitin ligase protein Listerin in mice which led to the conclusion that mutations in Listerin caused neurodegeneration. Kay's research on intercellular networks has the potential to contribute to drug therapies by identifying compounds that affect the circadian pathways. His findings and analyses of this mammalian oscillator contribute to our medical understanding of how

605-871: A study published in 2005 which used new RNAi genetic screening techniques to discover a non-coding RNA (ncRNA) known as NRON . NRON, a repressor of the protein NFAT , is one of the first well characterized examples of a ncRNAs involved in transcription regulation. In 2006, Hogenesch moved to the Perelman School of Medicine at the University of Pennsylvania where he continues to study mammalian circadian clocks and genome function. One of his current research directions includes incorporating research on noncoding RNA, such as siRNA or hairpin RNA isolated by combining forward genetics and genomic screens . He has used this technique on miRNA to examine signalling and cell survival. Over

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660-699: A suitable model plant, Arabidopsis thaliana and found that Cab mRNA levels are also under circadian control in Arabidopsis . He then developed Cab2:luc fusion, the fusion of luciferase open reading frame downstream of the Cab2 promoter region, as a marker for monitoring the circadian phenotype. This fusion marker was widely used in later studies and contributed enormously to the understanding of circadian rhythm regulation in Arabidopsis . Based on this Cab:luc fusion technology, Kay set up luciferase imaging assays for large scale forward genetics screening and identified

715-427: A variety of papers that cover a range of topics including CREB signaling, NF-κB signaling, TRP channels, melanopsin signaling, cell type specific splicing, noncoding RNA function, and RNA-seq methods and mapping algorithms. Hogenesh has pushed for the chronobiology community to create Misplaced Pages pages about genes through a project called Gene Wiki . The result has been the creation of pages about genes involved in

770-725: Is confirmed by the Council in April, and a secret ballot of Fellows is held at a meeting in May. A candidate is elected if they secure two-thirds of votes of those Fellows voting. An indicative allocation of 18 Fellowships can be allocated to candidates from Physical Sciences and Biological Sciences; and up to 10 from Applied Sciences, Human Sciences and Joint Physical and Biological Sciences. A further maximum of six can be 'Honorary', 'General' or 'Royal' Fellows. Nominations for Fellowship are peer reviewed by Sectional Committees, each with at least 12 members and

825-421: Is nominated by two Fellows of the Royal Society (a proposer and a seconder), who sign a certificate of proposal. Previously, nominations required at least five fellows to support each nomination by the proposer, which was criticised for supposedly establishing an old boy network and elitist gentlemen's club . The certificate of election (see for example ) includes a statement of the principal grounds on which

880-470: Is suppressed by the buildup of the PER:CRY heterodimers. After receiving his Ph.D. in 1999, Hogenesch followed his Ph.D. mentor Christopher Bradfield to the University of Wisconsin-Madison and continued in his lab as a postdoctoral associate. During this time, Hogenesch focused on following up on his Ph.D. work. Later in 1999, he became a postdoctoral associate with Steve A. Kay and Peter G. Schultz . Kay

935-568: The Genomics Institute of the Novartis Research Foundation to initiate new work on the mammalian clock. He and his postdoctoral fellow John B. Hogenesch , realized that in order to discover novel mammalian clock genes one would have to leverage high throughput genomics techniques that were being developed at the time. In 2002, Kay's group identified the novel photoreceptor melanopsin (Opn4) and how it worked in conjunction with

990-591: The University of Southern California in 1989 followed by a B.S. in Biology in 1991. He was inspired to study chronobiology by Joseph Takahashi in the fall of 1992 after learning about the Drosophila clock in a lecture. In 1999 Hogenesch completed a Ph.D. in Neuroscience at Northwestern University 's Chicago campus, studying transcription factors with basic helix-loop-helix ( BHLH ) and PAS protein domains . Hogenesh

1045-524: The University of Southern California . His father is a polymer chemist , and his mother is a clinical instructor in psychiatry and behavioral sciences . His brother, Tom Hogen-Esch is a Political Science and Urban Studies professor at Cal State Northridge . John is married to his longtime partner Kelly Schilling, and they reside in the Cincinnati area. Hogenesch originally received a B.A. in History from

1100-426: The post-nominal letters FRS . Every year, fellows elect up to ten new foreign members. Like fellows, foreign members are elected for life through peer review on the basis of excellence in science. As of 2016 , there are around 165 foreign members, who are entitled to use the post-nominal ForMemRS . Honorary Fellowship is an honorary academic title awarded to candidates who have given distinguished service to

1155-577: The Institute for Childhood and Neglected Diseases at the Scripps Research Institute. He also served as professor and chairman there in subsequent years. In addition to his academic experiences, Kay also founded biotechnology companies like Phenomix Corporation in 2003. In 2007, Dr. Kay became professor and then the dean of the biology department at the UC San Diego. From 2012 to 2015, he served as

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1210-469: The Program Manager of Genomics at GNF in 2000, and remained there until 2004. During his time there, he accomplished the compilation of the complete human transcriptome, and also the mRNA characterization of the human, mouse, and rat transcriptomes. These highly cited works, together cited over 3700 times, have been influential in the field of genome biology. Hogenesch then brought together his work on

1265-439: The Royal Society has been described by The Guardian as "the equivalent of a lifetime achievement Oscar " with several institutions celebrating their announcement each year. Up to 60 new Fellows (FRS), honorary (HonFRS) and foreign members (ForMemRS) are elected annually in late April or early May, from a pool of around 700 proposed candidates each year. New Fellows can only be nominated by existing Fellows for one of

1320-1395: The Society, the oldest known scientific academy in continuous existence, is a significant honour. It has been awarded to many eminent scientists throughout history, including Isaac Newton (1672), Benjamin Franklin (1756), Charles Babbage (1816), Michael Faraday (1824), Charles Darwin (1839), Ernest Rutherford (1903), Srinivasa Ramanujan (1918), Jagadish Chandra Bose (1920), Albert Einstein (1921), Paul Dirac (1930), Winston Churchill (1941), Subrahmanyan Chandrasekhar (1944), Prasanta Chandra Mahalanobis (1945), Dorothy Hodgkin (1947), Alan Turing (1951), Lise Meitner (1955), Satyendra Nath Bose (1958), and Francis Crick (1959). More recently, fellowship has been awarded to Stephen Hawking (1974), David Attenborough (1983), Tim Hunt (1991), Elizabeth Blackburn (1992), Raghunath Mashelkar (1998), Tim Berners-Lee (2001), Venki Ramakrishnan (2003), Atta-ur-Rahman (2006), Andre Geim (2007), Bai Chunli (2014), James Dyson (2015), Ajay Kumar Sood (2015), Subhash Khot (2017), Elon Musk (2018), Elaine Fuchs (2019) and around 8,000 others in total, including over 280 Nobel Laureates since 1900. As of October 2018 , there are approximately 1,689 living Fellows, Foreign and Honorary Members, of whom 85 are Nobel Laureates. Fellowship of

1375-655: The Society, we shall be free from this Obligation for the future". Since 2014, portraits of Fellows at the admissions ceremony have been published without copyright restrictions in Wikimedia Commons under a more permissive Creative Commons license which allows wider re-use. In addition to the main fellowships of the Royal Society (FRS, ForMemRS & HonFRS), other fellowships are available which are applied for by individuals, rather than through election. These fellowships are research grant awards and holders are known as Royal Society Research Fellows . In addition to

1430-581: The award of Fellowship (FRS, HonFRS & ForMemRS) and the Research Fellowships described above, several other awards, lectures and medals of the Royal Society are also given. John B. Hogenesch Hogenesch was born on May 29, 1967, in Rotterdam , Netherlands. He was raised in Gainesville, Florida , by his father Thieo E. Hogen-Esch and his mother Cheryl H. St. George. His parents both work at

1485-597: The cause of science, but do not have the kind of scientific achievements required of Fellows or Foreign Members. Honorary Fellows include the World Health Organization's Director-General Tedros Adhanom Ghebreyesus (2022), Bill Bryson (2013), Melvyn Bragg (2010), Robin Saxby (2015), David Sainsbury, Baron Sainsbury of Turville (2008), Onora O'Neill (2007), John Maddox (2000), Patrick Moore (2001) and Lisa Jardine (2015). Honorary Fellows are entitled to use

1540-466: The ccg of heads and bodies separately. Kay began his extensive research on mice in 1999 at the Genomics Institute of the Novartis Research Foundation , with a primary focus on melanopsin (Opn4) and visual photoreceptors. It was here, with the use of automation and large-scale genomics technology, that Kay and collaborating colleagues found that the mammalian clock consisted of more than just one feedback loop. In 2002, Kay and his team were able to show

1595-773: The circadian clock such as ARNTL , as well as pages about chronobiologists like Ingeborg Beling . He has also been instrumental in creating the Gene Atlas. This project uses a database run by Hogenesch called the Circa database that lists time of activity of genes in different tissues. As an open source database, it allows biologists and pharmaceutical researchers to determine the peak time of different genes and mRNA which can then be used to target drug treatments. In October 2014, Hogenesch's discovery that many proteins targeted by drugs experience circadian fluctuations made strides towards chronotherapy treatment. Further research has focused on

1650-435: The circadian regulation loop. He also profiled clock controlled genes (ccg) in Arabidopsis with several technologies and identified key pathways temporally controlled by circadian clock . His work on functional analyses of core clock genes, as well as ccg, successfully connected circadian rhythm with the control of development, like seedling, growth and flowering. His work on these clock genes contributed significantly to

1705-434: The clock controls downstream processes and holds clinical significance as a variety of diseases and biological processes are involved, such as aging, immune response, and metabolism. For instance, diabetes and the circadian clock may correlate based on the findings of circadian expression in the liver and glucose output. Using a cell-cased circadian phenotypic screen, Kay and a team of chronobiologist researchers identified

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1760-407: The course of his career, Hogenesch has made numerous contributions to the understanding of the core clock mechanisms. He discovered the key proteins Bmal1 ( Arntl ), and Bmal2 early in his career. He was also on the team that discovered Rora to be an important regulator of Bmal1 . Rora is currently under investigation for a possible connection to autism , which may relate to its function as

1815-481: The discovery and functional analysis of many photoreceptors , including phytochrome , cryptochrome , ZTL and LKP2 and their roles in circadian rhythms . Kay applied the first clock gene fusion, Per:luc, in Drosophila melanogaster which allows monitoring of its rhythm at the single animal level. Per:luc fusion also helped him understand the phase relationship in mRNA and protein oscillation. He further improved

1870-515: The fellowships described below: Every year, up to 52 new fellows are elected from the United Kingdom, the rest of the Commonwealth of Nations , and Ireland, which make up around 90% of the society. Each candidate is considered on their merits and can be proposed from any sector of the scientific community. Fellows are elected for life on the basis of excellence in science and are entitled to use

1925-427: The first short period mutant of TOC1 gene . TOC1 was proved to be a core clock gene in Arabidopsis and was cloned by Kay lab after a long period of time Kay also revealed the biochemical function of TOC1 and found that TOC1 and LHY/CCA1 reciprocally regulate each other, and further studied the mechanism of this regulation. Kay identified ELF3, GI, Lux, CHE and PRRs as core clock genes and studied their role in

1980-530: The good of the Royal Society of London for Improving Natural Knowledge, and to pursue the ends for which the same was founded; that we will carry out, as far as we are able, those actions requested of us in the name of the Council; and that we will observe the Statutes and Standing Orders of the said Society. Provided that, whensoever any of us shall signify to the President under our hands, that we desire to withdraw from

2035-537: The help of his student Andrew Millar , and subsequently identified TOC1 , the first clock gene identified in plants. He moved several times and became an associate professor in the biology department at the University of Virginia in 1996 where he joined the NSF Center for Biological Timing. 4 years later he moved to The Scripps Research Institute in La Jolla, Ca. There, Kay collaborated with Jeffrey C. Hall and discovered

2090-507: The human and mouse transcriptomes into a gene atlas, which he made available as a tool for other genome biologists. In addition to characterizing transciptomes present in various organisms, Hogenesch has also spent time throughout his career determining which genes were regulated on a circadian schedule. Working with his colleagues he has determined that mRNA in plants, flies, mice, and humans all shows extensive circadian regulation. In mammals up to 43% of all genes are regulated according to

2145-399: The laboratory of Christopher Bradfield, when he discovered five transcription factors in the basic helix-loop-helix-PAS (bHLH-PAS) domain superfamily during his thesis work. These transcription factors were initially named MOP1-5. Hogenesch’s later characterization of MOP3, better known as BMAL1 or ARNTL , revealed in 1998 that its role as a partner of the bHLH-PAS transcription factor CLOCK

2200-513: The light regulation of chlorophyll synthesis in plants. Kay learned that light changed gene expression, and that circadian clock was also regulating transcription on a daily basis. He would later spend more than two decades pursuing these circadian clocks. Following Griffiths' advice, Kay moved to the United States and worked as a postdoc in the Nam-Hai Chua lab at Rockefeller University. It

2255-420: The mathematical method of bioluminescence analysis and made the results quantified. In 1997, his Per promoter driven Green Fluorescent Protein (GFP) study suggested that Per is widely expressed throughout the fly body in a rhythmic pattern, and all body parts are capable of light perception. This is one of the first pieces of evidence for a peripheral self-sustaining circadian clock. In 1998, he proposed

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2310-509: The post nominal letters HonFRS . Statute 12 is a legacy mechanism for electing members before official honorary membership existed in 1997. Fellows elected under statute 12 include David Attenborough (1983) and John Palmer, 4th Earl of Selborne (1991). The Council of the Royal Society can recommend members of the British royal family for election as Royal Fellow of the Royal Society . As of 2023 there are four royal fellows: Elizabeth II

2365-546: The proposal is being made. There is no limit on the number of nominations made each year. In 2015, there were 654 candidates for election as Fellows and 106 candidates for Foreign Membership. The Council of the Royal Society oversees the selection process and appoints 10 subject area committees, known as Sectional Committees, to recommend the strongest candidates for election to the Fellowship. The final list of up to 52 Fellowship candidates and up to 10 Foreign Membership candidates

2420-470: The role of melanopsin , a photosensitive photopigment in retinal ganglion cells, in detecting light for the master circadian oscillator located in the suprachiasmatic nucleus (SCN) in the hypothalamus of the brain. Both melanopsin and visual photoreceptors , such as rods and cones, were required for entrainment . However, removing each individually did not result in total blindness in mice, as they retained non-visual photoreception. The enzyme luciferase

2475-604: The time of administration with respect to the circadian cycle. Fellow of the Royal Society Fellowship of the Royal Society ( FRS , ForMemRS and HonFRS ) is an award granted by the Fellows of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge , including mathematics , engineering science , and medical science ". Fellowship of

2530-463: The translational transcriptional feedback loop model of the circadian clock in flies, analogous to other labs that proposed a same model in mammals and fungi. Kay discovered that cryptochrome is the circadian photoreceptor that directly acts with and sequesters TIM in response to light. Kay did one of the pioneering microarray analyses to study clock controlled genes (ccg) , and revealed tissue-specific nature of circadian rhythms by analyzing

2585-481: The understanding of repression-based clock regulation loops in plants, which is distinct to the ones in animals that are composed of both positive and negative elements. Kay discovered the mechanism of seasonal time and day-length measurement and flowering time determination in Arabidopsis through the GI/FKF1-CO-FT pathway . Kay found evidence that there are multiple phototransduction pathways, and contributed to

2640-401: The visual photoreceptors. Kay's work, along with others in the field, on melanopsin was named one of "Science's" top 10 breakthroughs that year. Kay and Hogenesch also collaborated with Takahashi to define the mammalian circadian transcription and the large scale orchestration of gene expression by the circadian clocks in most tissues throughout the body. In 2001, Kay served as director for

2695-520: Was at the Nam-Hai Chua lab working with another postdoc named Ferenc Nagy that Kay stumbled upon the discovery that the chlorophyll binding gene CAB was regulated by a circadian clock. In 1989, Kay was appointed to his first faculty position as an assistant professor at Rockefeller University . While there, he collaborated with Michael W. Young to identify fly PER gene homologues, which did not exist. Kay then developed glowing Arabidopsis thaliana plants to screen for circadian rhythm mutants, with

2750-609: Was employed by the University of California at San Diego and the Scripps Research Institute , while Schultz was employed at the Scripps Research Institute and was founder and director of The Genomics Institute of the Novartis Research Foundation (GNF) in La Jolla , CA. Hogenesch started work on the human transcriptome and the mRNA characterization of the transcriptomes of humans, mice, and rats, which he would later continue as Director of Genomics at GNF. Hogenesch became

2805-559: Was essential to the function of the mammalian circadian clock. BMAL1 and CLOCK are now the two most well recognized bHLH-PAS domain transcription factors. Later work revealed that Bmal1 is the only clock gene without which the circadian clock fails to function in humans. BMAL1 functions as a positive element in the circadian clock. It forms a heterodimer with CLOCK to initiate transcription of target genes that contain E-box sequences, such as Period and Cryptochrome in mice. The BMAL1:CLOCK complex

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2860-501: Was mentored by Chris Bradfield, now a professor of oncology and the Director of the Molecular and Environmental Toxicology Graduate Program at the University of Wisconsin-Madison. He continued his research on functional genomics as a postdoctoral researcher with Dr. Steve A. Kay at the Genomics Institute of the Novartis Research Foundation . In March, 1997, Hogenesch was a neuroscience graduate student at Northwestern University in

2915-552: Was motivated to study a mouse mutant he co-discovered that modeled the disease his mother had. Thus, a tribute to his mother has led to the discovery of the gene Listerin, Ltn1, E3 ubiquitin ligase and its effect on motor and sensory neuron degeneration. In 1981, Steve Kay earned his bachelor's degree in Biochemistry at University of Bristol , UK. He stayed there in the Trevor Griffiths lab and received his PhD in 1985 exploring

2970-421: Was not a Royal Fellow, but provided her patronage to the society, as all reigning British monarchs have done since Charles II of England . Prince Philip, Duke of Edinburgh (1951) was elected under statute 12, not as a Royal Fellow. The election of new fellows is announced annually in May, after their nomination and a period of peer-reviewed selection. Each candidate for Fellowship or Foreign Membership

3025-571: Was utilized by Kay's lab to research clock gene expression in single culture cells and revealed that a variety of cells, including those of the liver and fibroblasts, demonstrate circadian rhythm . As time went on, these rhythms became increasingly out of phase as local oscillators desynchronized and each cell expressed their own pace. In 2007, these findings demonstrated the need to examine single-cell phenotypes along with behaviors of experimental clock mutants. In 2009, inspired by his mother's fatal motor neuron disease, Kay and some colleagues performed

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