2016年度「邵逸夫獎」 The Shaw Prize 2016
「邵逸夫獎」為國際性獎項，得獎者應仍從事於有關的學術領域，在學術研究、科學 研究及應用上有傑出貢獻，或在近期獲得突破性的成果，或在其他領域有卓越之成 就。評選的原則主要考慮候選人之專業貢獻能推動社會進步，提高人類生活質素， 豐富人類精神文明。
「邵逸夫獎」設有三個獎項，分別為天文學獎、生命科學與醫學獎和數學科學獎， 每項獎金一百二十萬美元。除獎金外，各得獎者還獲頒獎章及證書一份。提名及評 審程序於每年九月開始，翌年夏季宣佈得獎人名單，並於同年秋季舉行頒獎典禮。 邵逸夫獎獎章 「邵逸夫獎」是按邵逸夫先生的意願而設，於2002年11月宣告成立，以表彰在學術及科學研 The Shaw Prize medal 獎章正面的肖像是此獎項的創立人邵逸夫 究或應用上獲得突破成果，和該成果對人類生活產生意義深遠影響的科學家，原則 先生，背面則刻上得獎年份、獎項類別、得獎 是不論得獎者的種族、國籍、性別和宗教信仰。 者的姓名及在右上方的「制天命而用之」的印 鑑。印鑑上是中國戰國時代思想家荀子（公元 前313至公元前238）的命題，意思是人類能 「邵逸夫獎」由邵逸夫獎基金會管理及執行。各獎項的評審委員會由國際知名科學 掌握及運用自然法則。 家組成，負責評審工作。 The front of the medal displays a portrait of Mr Run Run Shaw, the founder of this award. The Shaw Prize is an international award to honour individuals who are currently active in On the reverse, the medal shows the award category, the relevant year and the name of the their respective fields and who have recently achieved distinguished and significant laureate, and an imprint of a seal of the Chinese advances, who have made outstanding contributions in academic and scientific research phrase ”制天命而用之” on the upper right corner. It is quoted from Xun Zi – a thinker in the or applications, or who in other domains have achieved excellence. The award is Warring States period of Chinese history in 313 - 238 B.C.E., meaning “Grasp the law of nature dedicated to furthering societal progress, enhancing quality of life, and enriching and make use of it”. humanity’s spiritual civilisation.
The Shaw Prize consists of three annual awards: the Prize in Astronomy, the Prize in Life Science and Medicine, and the Prize in Mathematical Sciences. Each prize carries a monetary award of one million two hundred thousand US dollars and each winner receives a medal and a certificate. The nomination process begins in September. The winners are announced in the summer and the prizes are presented in autumn in the following year.
Established under the auspices of Mr Run Run Shaw in November 2002, the Prize honours individuals, regardless of race, nationality, gender and religious belief, who have achieved significant breakthroughs in academic and scientific research or applications and whose work has resulted in a positive and profound impact on mankind.
The Shaw Prize is managed and administered by The Shaw Prize Foundation based in Hong Kong. The important role of adjudication of candidates for the prizes is undertaken by an international team of reputable scientists who serve on the Selection Committees.
SHAW16-01-INTRO 2016年度邵逸夫天文學獎 The Shaw Prize in Astronomy 2016
2016年度「邵逸夫天文學獎」平均頒予羅奈爾特·德雷弗（Ronald W P Drever）、基普·索恩（Kip S Thorne）和 雷納·韋斯（Rainer Weiss），以表彰他們對「激光干涉儀重力波觀測站」LIGO的構思和設計。LIGO最近首次直接觀測 到重力波，為天文探索開創了一個新方法，而首先偵測到的非凡事例為兩個星級質量的黑洞合併。 The Shaw Prize in Astronomy 2016 is awarded in equal shares to Ronald W P Drever, Kip S Thorne and Rainer Weiss for conceiving and designing the Laser Interferometer Gravitational-Wave Observatory (LIGO), whose recent direct detection of gravitational waves opens a new window in astronomy, with the first remarkable discovery being the merger of a pair of stellar mass black holes.
得獎人簡介 Biographical Notes of Laureates
羅奈爾特．德雷弗 基普．索恩 雷納．韋斯 Ronald W P Drever Kip S Thorne Rainer Weiss
羅奈爾特．德雷弗（Ronald W P Drever） 基普．索恩（Kip S Thorne）1940年出生於美國 雷納．韋斯（Rainer Weiss）1932年出生於德國 1931年出生於英國格拉斯哥，為美國加州理工 猶他州洛根市，為美國加州理工學院費曼理論 柏林，現為美國麻省理工學院物理學榮休教 學院物理學榮休教授。1953年於英國格拉斯哥 物理學榮休教授。1962年於加州理工學院取 授。1955年和1962年分別於美國麻省理工學 大學取得理學士學位，並於1958年於該校取得 得物理學學士學位，並於1965年於美國普林 院取得物理學學士和物理學博士學位。他曾於 自然哲學博士學位。他在加州理工學院分別擔 斯頓大學取得物理學博士學位。1966年回到 美國塔夫茨大學分別擔任導師（1960–1961） 任客座硏究員（1977）、教授（1979–2002）和 加州理工學院，最初擔任研究員，1967年至 和物理學助理教授（1961–1962），之後於 榮休教授（2002–）。他是美國人文與科學院 1970年為副教授，1970年為理論物理學教 1962年至1964年期間在美國普林斯頓大學擔任 院士及愛丁堡皇家學會院士。 授，1981年至1991年為威廉．凱南講座教 物理學研究員。隨後，他加入美國麻省理工學 授，1991年至2009年為費曼理論物理學講座 院物理系任教，於1964年至1967年為助理教 Ronald W P Drever was born in 1931 in Bishopton, Glasgow, UK and is Professor of 教授，自2009年起為費曼理論物理學榮休講 授，1967年至1973年為副教授，1973年至2001 Physics, Emeritus, at the California Institute of 座教授。他是美國國家科學院院士及美國人文 年為教授，自2001年起為榮休教授。他是美國 Technology (Caltech), USA. He received his 與科學院院士。 國家科學院院士及美國人文與科學院院士。 Bachelor of Science in 1953 and his PhD in Kip S Thorne was born in 1940 in Logan, Utah, Rainer Weiss was born in 1932 in Berlin, Germany Natural Philosophy in 1958 from the University of USA and is the Feynman Professor of Theoretical and is currently Professor Emeritus in Physics at the Glasgow, UK. He served as a Visiting Associate in Physics, Emeritus, at the California Institute of Massachusetts Institute of Technology (MIT), USA. 1977 and was successively Professor (1979–2002) Technology (Caltech), USA. He received his He received his Bachelor of Science in Physics in and Professor Emeritus (2002–) at Caltech. He is a Bachelor of Science in Physics from Caltech in 1962 1955 and his PhD in Physics in 1962 from MIT. He Fellow of the American Academy of Arts and and his PhD in Physics from Princeton University, was an Instructor and Assistant Professor of Physics Sciences and the Royal Society of Edinburgh. USA in 1965. He returned to Caltech, first as a at Tufts University, USA from 1960 to 1961 and Research Fellow (1966–1967), and then from 1961 to 1962 respectively. He served as successively as Associate Professor (1967–1970), Research Associate in Physics at Princeton Professor in Theoretical Physics in 1970, the University, USA from 1962 to 1964. He then joined William R Kenan, Jr. Professor (1981–1991), the MIT, where in the Department of Physics he was Feynman Professor of Theoretical Physics successively Assistant Professor (1964–1967), (1991–2009), and the Feynman Professor of Associate Professor (1967–1973), Professor Theoretical Physics, Emeritus (2009–). He is a (1973–2001) and Professor Emeritus (2001–). He member of the US National Academy of Sciences is a member of the US National Academy of Sciences and the American Academy of Arts and Sciences. and the American Academy of Arts and Sciences.
SHAW16-02-AST 突破性的發現 The Revolutionary Discovery
2015年9月14日，激光干涉儀重力波觀測站（LIGO）的兩個探測器同時觀測到一個重力波信號。該信號的波形，與 廣義相對論預測一對黑洞合併所產生的重力波形吻合。科學家估計合併前的黑洞質量分別約為太陽的29和36倍， 合併在13億年前發生。約三倍太陽質量的物質，在瞬間轉化成重力波。觀察結果表明與恆星質量相約的雙黑洞系 統確實存在，這亦是首次直接探測到重力波及首次觀察到雙黑洞合併。
羅奈爾特．德雷弗、基普．索恩及雷納．韋斯是負責構思和設計LIGO的核心人物。LIGO最近直接探測到重力波， 為物理學開創了一個新方法，去研究極強引力下的現象，當中巨大質量的天體以接近光速運動，在時空中產生非 線性波動。
LIGO的發現被譽為天文學上最重要的發現之一，其重要性可從多個角度說明。簡而言之，以往只能通過電磁輻射 或高能粒子觀察宇宙，現在LIGO卻提供了第三個方法。因此，LIGO創建了一個全新的天文學分支，在完全缺乏其 他天文信號的情況下，都能讓我們觀察和研究天文現象。這項新方法帶來革命性的影響，猶如射電天文學當年出 現，脈衝星和類星體才跟着被發現。
廣義相對論的一個基本預測是重力波的存在，而如今LIGO直接觀測到重力波，證明這種基於因果律的預測是正確 的。然而，LIGO的發現的重要性不在於證實時空會呈現微弱波動，因為通過雙星系統內脈衝星軌道所呈現的衰 減，這早已被間接地證實。其真正的意義在於：透過追蹤強大和隨時間變化的重力波來源，可揭示黑洞的特性。
On 14 September 2015, the two detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) simultaneously observed a gravitational-wave signal. The signal matches the waveform predicted by general relativity for the merger of a pair of black holes. Scientists estimate that the black holes for this event were about 29 and 36 times the mass of the Sun, and the 黑洞合併時所產生的時空漣漪 event took place 1.3 billion years ago. About three times the mass of the Sun was converted into gravitational waves in a （計算模擬）。 Ripples in spacetime created by merging fraction of a second. These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first black holes (numerical simulation). direct detection of gravitational waves and the first observation of a binary black hole merger.
Ronald Drever, Kip S Thorne and Rainer Weiss are the primary figures responsible for the conception and design of LIGO. LIGO’s recent direct detection of gravitational waves represents the first probe of physics in the limit of strong gravity, where massive objects moving at velocities close to that of light drive nonlinear waves in spacetime.
LIGO’s discovery ranks among the most significant ever made in astronomy, and its importance can be viewed from a number of distinct perspectives. Most simply, LIGO has provided a third strand to the means by which we can observe the universe, in addition to electromagnetic radiation or energetic particles. LIGO has thus established an entirely new branch of astronomy, allowing us to study phenomena where signals from existing astronomical messengers are entirely lacking. The impact of this new tool seems likely to be as revolutionary as, for example, the opening up of radio Credit: R. Hurt/Caltech-JPL astronomy and the subsequent discovery of pulsars and quasars.
The direct observation of gravitational radiation validates a basic prediction of general relativity, showing such fundamental expectations based on causality to be correct. However, LIGO’s results go much beyond the weak spacetime fluctuations already inferred from the orbital decay of pulsars in binary systems. By probing the region of strong and time-dependent gravitational fields from which the waves originate, they reveal remarkable properties of black holes.
Credit: Caltech/MIT/LIGO Lab
激光干涉儀重力波觀測站（LIGO） 的L形探測器 The L-shaped detector of the Laser Interferometer Gravitational-Wave Observatory
SHAW16-03-AST 什麼是重力波？ What Are Gravitational Waves?
1916年，愛因斯坦在廣義相對論中首次預測重力波 ─ 時空漣漪的存在。重力波以光速傳播。當巨大質量的天體 互相圍繞運行或碰撞時，它們會擾亂周圍的時空，就像石頭扔進一潭靜水般。通過研究這些波，天文學家希望了 解產生它們的天文現象，這些往往是由看不到的天體（如黑洞）所引致。重力波傳播到觀測站時，已經變得極為 微弱，所以極難探測。
In 1916, Albert Einstein in his general theory of relativity first predicted the existence of gravitational waves — ripples in the fabric of spacetime. Gravitational waves travel at the speed of light. When massive objects move around or collide with one another, they disturb the surrounding spacetime like a pebble tossed into a still pond. By studying these waves, astronomers hope to learn about the cosmic phenomena that create them, which are often “invisible” objects such as black holes. The gravitational waves are extremely weak when they reach us, so are very difficult to detect.
LIGO運作原理 How LIGO Works
當重力波經過時空，會令物體的位置產生極輕微但可被探測的變動。LIGO的設計 就是利用了這個原理：它的兩個檢測器每個具有雙臂，形成直角，共設有三面反射 鏡，雙臂的盡頭各設一面，而另一面則安裝在雙臂的相交位置。雙臂長度相同，激 光由鏡子反射到光電探測器。正常情況下，激光在雙臂運行的距離相同，LIGO的 設定讓激光在中心相遇時，它們的光波的相位剛好相反，因而互相抵消，沒有光到 達光電探測器。當重力波穿過檢測器時，其中一臂將變得稍長，而另一臂將變得稍 短，於是通過雙臂運行的兩束光會出現相位差。當兩束激光相遇，這樣的相位差便 形成干涉圖案，揭示了重力波的存在。
檢測器的雙臂越長，激光所走的距離越遠，儀器對長度的改變便越敏感。LIGO的 目標是測量雙臂長度少於質子大小10,000倍的變化。它臂長四公里，激光來回反射 約280次，才與來自另一臂的激光匯合，這樣可使激光行走的距離增至1,120公 里，顯著提高檢測器的靈敏度。兩個相同的探測站分別設於美國華盛頓州漢福德和 路易斯安那州利文斯頓，等待由雙星系統或超新星爆炸所造成的重力波。兩站相距 超過3,000公里，以確保局部地區的震動，例如小型地震所產生的震動，不會被誤
以為是由重力波所引起。 LIGO的干涉儀 The interferometer of LIGO Gravitational waves cause incredibly small but detectable distortions in the positions of objects in the spacetime through which they pass. LIGO's design takes advantage of this fact: Its two L-shaped detectors have three mirrors, one at the end of each arm and one at the point where the arms meet. The two arms are the same length. Laser beams bounce off the mirrors back to a photo detector. LIGO is set up so that normally, when both laser beams travel the same distance, their light waves are exactly out of phase and cancel out each other when they meet at the centre and no light hits the photo detector. If a gravitational wave passes through the detector, however, one arm will become slightly longer whereas the other arm will get slightly shorter, causing the light travelling through the two arms to have a phase difference. Such a mismatch creates an interference pattern when the two laser beams meet, thus revealing the gravitational wave's presence.
The longer the arms, the farther the laser travels, and the more sensitive to length changes the instrument becomes. LIGO attempts to measure a change in arm length 10,000 times smaller than a proton. Its arms are 4 km long. By bouncing the laser beam about 280 times before it finally merges with the beam from the other arm, the distance travelled by each laser beam is increased to 1,120 km and the sensitivity of the detector is dramatically increased. Twin facilities, one in Hanford, Washington, and the other in Livingston, Louisiana, USA, wait for gravitational waves caused by binary systems or supernovae. The two sites are located more than 3,000 km apart to ensure that local vibrations, such as that caused by a micro-earthquake, are not mistaken for signals from gravitational waves.
正常運作時（黃色），分別來自LIGO兩條管道的兩束光相 遇，兩組光波互相抵消，結合起來變成黑暗。如果重力 波改變了兩條管道的相對長度（藍色），兩組光波將會有 所不同，結合起來將會顯示探測到信號。 During normal operations, when the beams from the two arms of LIGO recombine (yellow), the waves should cancel each LIGO技術人員檢查其中一個 other out, rendering the resultant beam dark. If a gravitational 干涉儀的鏡子。 wave changes the relative length of the arms (blue), the waves LIGO technician inspects one of will not match up, and the combined beams will reveal signals. Credit: Caltech/MIT/LIGO Lab the interferometer's mirrors.
SHAW16-04-AST 2016年度邵逸夫生命科學與醫學獎 The Shaw Prize in Life Science and Medicine 2016
2016年度「邵逸夫生命科學與醫學獎」平均頒予艾德里安•伯德（Adrian P Bird）和胡達•佐格比（Huda Y Zoghbi）， 以表彰他們發現一類基因和蛋白，這些蛋白能夠確認染色體脫氧核醣核酸一種可以影響基因調控的化學改變；並確立 這基因的突變是發育障礙疾病蕾特氏症的主要成因。 The Shaw Prize in Life Science and Medicine 2016 is awarded in equal shares to Adrian P Bird and Huda Y Zoghbi for their discovery of the genes and the encoded proteins that recognise one chemical modification of the DNA of chromosomes that influences gene control as the basis of the developmental disorder Rett syndrome.
得獎人簡介 Biographical Notes of Laureates
艾德里安．伯德 胡達．佐格比 Adrian P Bird Huda Y Zoghbi
艾德里安．伯德（Adrian P Bird）1947年於英 胡達．佐格比（Huda Y Zoghbi）1954年於黎 國伍爾弗漢普頓出生，現為英國愛丁堡大學布 巴嫩貝魯特出生，現為美國貝勒醫學院兒科及 坎南遺傳學講座教授。1970年於蘇塞克斯大學 分子與人類遺傳學教授、德克薩斯兒童醫院珍 取得生物化學理學士學位，並於1972年於愛丁 與丹．鄧肯神經科學研究院主任，及美國霍華 堡大學取得生物化學博士學位。他曾在耶魯大 德休斯醫學研究所研究員。1975年於黎巴嫩貝 學和蘇黎世大學擔任博士後研究員 魯特美國大學取得生物學理學士學位，並於 （1972–1975）。之後他加入MRC哺乳動物基 1979年於美國田納西州納什維爾之梅哈里醫學 因組研究中心（1975–1986），然後轉到維也 院取得醫學博士學位。於1979年至1982年 納分子病理學研究所擔任資深科學家 間，她在貝勒醫學院和德克薩斯兒童醫院擔任 （1987–1990）。自1990年起，他於愛丁堡大 駐院醫生，隨後在貝勒醫學院從事博士後研究 學擔任布坎南遺傳學講座教授。他在愛丁堡協 員（1982–1988）。之後她一直在貝勒醫學院 助創辦威康信託細胞生物學中心，並兼負中心 兒科系任教，由助理教授（1988–1991）至副 主任一職（1999–2011）。隨後，他成為威康 教授（1991–1994），自1994年起為教授。她 信託基金會理事（2000–2010），其間於2007 是美國國家科學院及美國國家醫學院院士。 年至2010年為副主席。他是英國倫敦皇家學 Huda Y Zoghbi was born in 1954 in Beirut, 會、愛丁堡皇家學會及英國醫學科學院院士。 Lebanon and is currently Professor of Pediatrics & Adrian P Bird was born in 1947 in Wolverhampton, Molecular and Human Genetics at Baylor College UK and is currently the Buchanan Professor of of Medicine, Director of Jan and Dan Duncan Genetics at the University of Edinburgh, UK. He Neurological Research Institute, Texas Children’s obtained his Bachelor of Science in Biochemistry Hospital and an Investigator of the Howard Hughes from the University of Sussex in 1970 and his PhD Medical Institute, USA. She obtained her Bachelor in Biochemistry from the University of Edinburgh in of Science in Biology from American University of 1972. He was a Postdoctoral Fellow at the Beirut, Lebanon in 1975 and her MD from Meharry University of Yale and University of Zurich Medical College, Nashville, Tennessee, USA in (1972–1975). He joined the MRC Mammalian 1979. She was a medical resident of Baylor College Genome Unit (1975–1986) and then moved to of Medicine and Texas Children’s Hospital Vienna, where he served as a Senior Scientist in (1979–1982) and then a Postdoctoral Fellow at the Research Institute for Molecular Pathology Baylor College of Medicine (1982–1988). From (1987–1990). He has held the Buchanan Chair of 1988, she was successively Assistant Professor Genetics at the University of Edinburgh since 1990. (1988–1991), Associate Professor (1991–1994) He helped create the Wellcome Trust Centre for and Professor (1994–) in the Department of Cell Biology in Edinburgh and became its Pediatrics of Baylor College of Medicine. She has Director (1999–2011). Subsequently, he served been elected to the US National Academy of as a Governor (2000–2010) of the Wellcome Sciences and the National Academy of Medicine, Trust including a term as Deputy Chairman USA. (2007–2010). He is a Fellow of the Royal Society of London and Edinburgh and the Academy of Medical Sciences, UK.
SHAW16-05-LIFE 什麼是蕾特氏症? What Is Re Syndrome?
蕾特氏症是一種罕見的遺傳性X染色體連鎖神經發育疾病，患者通常為女性，發生率約為一萬分之一。病童初期能正常發育，一般 在半歲至一歲後開始發病，逐漸出現溝通技巧、活動能力、語言表達及手部運動技巧嚴重退化和下列症狀。患者壽命視乎發病時間和症狀的嚴重性。一般而 言，大部分患者可存活至40至50歲。目前，此症尚無根治方法，治療的主要目標是透過物理治療、職業治療及語言治療等，以舒緩症狀。
Rett syndrome is a rare genetic disease in the development of neurons, with an incidence of 1 in 10,000. It is an X-linked disease that affects females almost exclusively. Patients can usually develop normally until half to one year old, then gradually lose the communication capability, locomotion capability, speech capability and purposeful use of hand, and develop the symptoms as listed below. Life expectancy depends on when symptoms first begin and their severity. On average, most patients may survive into their 40s or 50s. Currently, there is no cure for Rett syndrome. Treatments, such as physical therapy, occupational therapy and speech therapy, etc, are targeted to relieve the symptoms.
The clinical symptoms and progression stages of Rett syndrome:
年齡 Age 發展停滯期 1 Developmental stagnation （6-18 個月 months） 1 急性退化期 • 發展停滯 2 Growth arrest Rapid regression （1-3 歲 years old） • 頭部發育減緩 Decreasing head growth 2 • 出現類自閉症行為 • 對遊戲和環境失去興趣 With autistic-like features Loss of interests in games and surroundings • 喪失手部使用功能、語言及社交能力 • 肌肉張力低，表徵如需要很大的力氣 Loss of hand skills, speech and social 才能維持身體直立 interaction Hypotonia, requiring extra effort to hold 3 the body upright • 癲癇 Seizures • 手部出現重覆性動作(如擰、、洗 、拍 敲) Start stereotypic hand movements 4 (e.g. wringing, washing, clapping, tapping) • 出現不規則呼吸 Have breathing irregularities • 畸形小頭 Abnormal small head 5 正常大小的頭部 Normal head size 假性穩定期 3 畸形小頭 Pseudostationary stage Abnormal small head （2-10 歲 years old） 6 • 行為問題有所改善，如對環境感興趣、 類自閉症行為減少及具較好的溝通能力 Has improvements in behaviour, with more interests in surroundings, less autistic-like 7 features and better communication skills • 脊柱側彎 Scoliosis • 自主神經功能障礙 8 Autonomic dysfunction 部分患者症狀停留在此階段， 並停止惡化。 Some patients’ symptoms retain in this stage and stop deteriorating. 9
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運動惡化後期 4 Late motor deterioration 11 （10 歲以後 After 10 years old）
• 抽搐頻率減少 Reduced seizures 12 • 減少或失去移動能力，需坐輪椅 Decrease or loss of mobility, wheelchair-bound • 出現柏金遜症症狀 13 Develop Parkinsonian features
SHAW16-06-LIFE 艾德里安．伯德的貢獻 Contributions of Adrian P Bird
發現MeCP2蛋白 ─ 一種能辨識神經細胞的基因「播放清單」的蛋白 Discovery of MeCP2 protein – a protein that recognises the “playlist” of genes in neuron cells
細胞 Cell 人體裏每一個細胞均具有一套完整的遺傳信息，約有30,000個基因；而不同的基 細胞核 Nucleus 因會按精確次序被開啟或關閉，以發育成為不同的細胞種類。比方說，人體細胞 染色體 Chromosome 是一部音樂播放器，它儲存了30,000首歌曲（基因）。當它要發育成一個神經細 胞時，它就會按一張特定的「播放清單」播放歌曲 （基因），這清單會標記着那首 染色質 Chromatin 歌曲（基因）會被播放及其播放的次序。若這「播放清單」出錯了，這細胞便不能 8個組蛋白 Histones 發育成正常的神經細胞。 核小體 Nucleosome 要製作這「播放清單」，其中一種方法是在脫氧核醣核酸（DNA）上或基因調控蛋 甲基連接在胞嘧啶 乙醯基連接在組蛋白 （關閉基因的標記） 基因 Gene （開啟基因的標記） 白上加上或去除小化學標記。艾德里安．伯德的研究團隊設計了一套方法來追蹤 Binding of methyl group on Binding of acetyl group on histones cytosine residues (A marker to turn on the gene) 其中一種稱為甲基（紅色五邊形）的化學標記。當甲基連接在DNA的胞嘧啶時， (A marker to turn off the gene) 基因 Gene 便標誌着要關閉這基因。另一種化學標記是乙醯基 （綠色六邊形），當它連接在組 蛋白時，便標誌着要開啟這基因。 在二十世紀九十年代，伯德的研究團隊發現了五種蛋白，它們能辨識甲基胞嘧 乙醯基 Acetyl group (-COCH3) 啶，並關閉被標記的基因。當中的MeCP2蛋白更能與酶結合成複合體，除去組 甲基 Methyl group 蛋白上的乙醯基。這兩種標記（甲基胞嘧啶和缺乙醯基組蛋白）同時存在成為關閉 (-CH3) 基因的強烈信號。
DNA在染色體內的組織及化學標記對 Every human cell contains a complete set of genetic information (around 30,000 genes), while different genes are turned on and 啟動基因的影響 off in a precise order during the development into different cell types. As an analogue, the human cell is a music player containing Organisation of DNA in chromosome and the effect of chemical tags on gene files of 30,000 songs (genes). To develop into a normal neuron cell, a specific “playlist” is made to determine which songs (genes) activation are “played” and in what order. If the “playlist” is wrong, the cell is going to develop into an abnormal neuron cell. One way to make such “playlists” is by adding and removing small chemical tags to DNA or 機制 Mechanism 1 proteins that can regulate gene function. The 連接在胞嘧啶的甲基 research group of Adrian Bird devised a method Methyl group binding on cytosine residues for tracing an important chemical tag, namely 關閉 Off methyl group (the red pentagon), that can modify MeCP2 the cytosine residues in DNA and serves to mark some genes to be turned off. Another chemical tag, acetyl group (the green hexagon) on histones, 基因 Gene serves to mark some genes to be turned on. In the 1990s, Bird’s research group uncovered five 機制 Mechanism 2 different proteins that recognise the methyl-C and 在組蛋白上的乙醯基 Acetyl group on histones work to turn off the gene. One of which, MeCP2 MeCP2 protein, further forms complex with enzymes to 開啟 On MeCP2 remove the acetyl groups from histones. These 關閉 Off two tags (methyl-C in DNA and the absence of acetyl groups on histones) cooperate to reinforce 基因 Gene an “off” signal on genes.
MeCP2蛋白關閉基因的機制 The mechanisms of MeCP2 protein turning off genes
知多一點點 ⋯ Did you know ... 組蛋白 Histones 組蛋白是在細胞核裏的一種呈正極的蛋白。呈負極的DNA分 子會纏繞八個組蛋白1.65個圈形成核小體。一連串核小體排 列並壓縮成染色質，染色質再進一步壓縮為染色體。人體細 胞核中共有46條染色體。因此，組蛋白讓細胞可將長達1.8 米的DNA擠進細小的細胞核中。 Histones are a family of positively-charged proteins in the nucleus. The negatively-charged DNA strand winds up 1.65 times around eight histone proteins to form structural units called nucleosomes. Nucleosomes fold up to form chromatin fibers which are then folded and coiled into chromosomes. There are 46 chromosomes in the nucleus of a human cell. Therefore, histones play a key role in squeezing approximately 1.8 metres of DNA into a tiny nucleus.
SHAW16-07-LIFE 胡達．佐格比的貢獻 Contributions of Huda Y Zoghbi
證明MECP2基因突變是蕾特氏症的病因 Proved mutations in MECP2 gene being the primary cause of Rett syndrome
蕾特氏症的病因長久被爭議。由於患者通常是女性，因此胡達．佐格比懷疑此症是由X連鎖的基因突變所引致，這 突變發生在男性時則會致命。要找出蕾特氏症的遺傳機制是非常困難，因為此症只有極少的病例，及99%以上已知 的病例均是零星出現，即在整個家族中只有一位成員患病。 在1999年，佐格比從極之罕有的蕾特氏症家族病例中，證明了MECP2基因突變便是蕾特氏 症的病因。這突破性的發現成為了蕾特氏症研究的轉捩點，也令我們可使用簡單直接的基 因測試作分子診斷，不再只憑雜亂的症狀作臨牀診斷。目前，已知這突變基因會導致多種 神經失調，包括自閉症和兒童精神分裂症。 及後，佐格比和伯德的研究團隊均積極地研究MeCP2蛋白所控制的表觀遺傳機制，和不同 MECP2基因的突變點對蕾特氏症症狀發展的影響。兩個研究團隊也獨立地利用轉基因技 術，令老鼠的MECP2基因產生突變，並出現蕾特氏症的主要症狀。這些蕾特氏症老鼠成為 研究的重要部分，幫助剖析MeCP2蛋白調控網絡和測試新的蕾特氏症治療法。 The origin of Rett syndrome has long been debated. As it is mainly seen in females, Huda Zoghbi suspected it to be caused by an X-linked mutation that is lethal in males. It was difficult to identify the genetic basis due to the rare occurrence of Rett syndrome cases and the fact that more than 99% of the cases are sporadic (only one member in the family is affected with the disorder).
蕾特氏症老鼠成為研究的重要部分，幫 The turning point for Rett syndrome research came with the discovery by Zoghbi in 1999. Using information from rare familial 助剖析MeCP2蛋白調控網絡和測試新的 Rett syndrome cases, she discovered mutations in MECP2 gene are the primary cause of Rett syndrome. Her discovery allowed 蕾特氏症治療法。 Rett syndrome mice become an important a confusing set of symptoms to be turned into a straightforward diagnostic genetic test of the disease. Mutations in MECP2 part of the research for dissecting the gene are now known to cause a variety of neuropsychiatric features ranging from autism to juvenile-onset schizophrenia. MeCP2 protein-mediated networks and testing new Rett syndrome therapies. Later on, the Zoghbi and Bird groups carry out extensive studies to delineate the complicated epigenetic mechanisms controlled by MeCP2 proteins, and the effects of MECP2 mutations on the development of Rett syndrome. Both groups independently created transgenic mice with various mutations on MECP2 gene, and reproduced the major symptoms of Rett syndrome in mice. These Rett syndrome mice become an important part of the research in dissecting the MeCP2 protein-mediated networks and testing new Rett syndrome therapies.
知多一點點 ⋯ Did you know ... 表觀遺傳學 Epigenetics
表觀遺傳學主要是研究不涉及DNA序列改變的遺傳機制。它 主要是透過在染色體上添加化學標記，以編制特定的「基因 播放清單」來開啟或關閉各個基因。換言之，傳統的遺傳學 是探討將DNA序列遺傳到下一代的機制，而表觀遺傳學就是 探討將基因使用方法遺傳到下一代的機制。 Epigenetics is the study of inheritance by mechanisms other than the DNA sequences in genes. It mainly works through chemical tags added to chromosomes to make specific “gene playlists” in order to switch genes on or off. In other words, traditional genetics describes the way of DNA sequences in genes passing from parents to children, and epigenetics describes passing on the way the genes are used.
SHAW16-08-LIFE 治療新方向 New Directions to Develop Treatment
研究人員在蕾特氏症老鼠身上發現，缺乏MeCP2蛋白的神經細胞並不是永久受損。伯德的研究團隊將具正常功能 的MeCP2蛋白引入已成年的蕾特氏症老鼠，它們可恢復正常。他們更發現神經細胞含有大量的MeCP2蛋白，其 水平與組蛋白相若，因此只要MeCP2蛋白的功能略為改變，便會對腦部細胞的染色體結構造成深遠的影響。
佐格比的研究團隊發現MeCP2蛋白是多種神經細胞正常運作的關鍵，腦部對MeCP2蛋白水平的些微升降均很敏 感。如在老鼠引入雙倍水平的MeCP2蛋白，該老鼠會逐漸出現如蕾特氏症般的神經失調症狀。而她們更利用遺傳 工程技術，將患有MECP2複製綜合症的成年老鼠的MeCP2蛋白調回正常水平，使牠們回復正常。目前，已知約有 1%的智力障礙症和自閉症病例是由MECP2複製綜合症所引起，此症患者通常為男性。
以上的研究展示了表觀遺傳學對神經生物學的深遠影響，也為利用基因治療來根治蕾特氏症和MECP2複製綜合症 帶來曙光。這些互補的研究再次證明基礎科學是揭示人類發展和疾病因由的重要基礎。
Using Rett syndrome mice, it is found that MeCP2-deficient neurons are not permanently damaged. Bird’s group showed that the Rett syndrome mice could be restored to normal by reintroducing the functional MeCP2 proteins in adult animals, even though they were already symptomatic. His group also found that the MeCP2 protein is quite abundant in nerve cells, approaching the level of the major chromosome-binding histones. A change in MeCP2 function is thus likely to have a profound effect on chromosome structure in the brain.
Zoghbi’s group showed that MeCP2 protein is critical for the normal function of many different types of neurons and that the brain is sensitive to relatively modest increases or decreases in the levels of MeCP2 protein. In fact, doubling MeCP2 protein levels causes a progressive neurological syndrome in mice that is as severe as Rett syndrome. Her group was able to reverse this disorder in adult mice with duplication syndrome by using genetic engineering technique to normalise MeCP2 levels. MECP2 duplication syndrome, which primarily affects male children, is now known to account for about 1% of cases of intellectual disabilities and autism.
These discoveries showed the profound importance of epigenetics to neurobiology and shed light on a path to treat Rett syndrome and MECP2 duplication syndrome using gene therapy. These highly complementary studies show, once again, the power of basic science to uncover the fundamental basis of human development and diseases.
SHAW16-09-LIFE 2016年度邵逸夫數學科學獎 The Shaw Prize in Mathematical Sciences 2016
2016年度「邵逸夫數學科學獎」頒予奈傑爾·希欽（Nigel J Hitchin），以表彰他對幾何學、表示論和理論物理學作出 極重要貢獻。他引入了基本而優美的概念和技術，影響深遠。 The Shaw Prize in Mathematical Sciences 2016 is awarded to Nigel J Hitchin for his far-reaching contributions to geometry, representation theory and theoretical physics. The fundamental and elegant concepts and techniques that he has introduced have had wide impact and are of lasting importance.
得獎人簡介 Biographical Notes of Laureate
奈傑爾．希欽 Nigel J Hitchin
奈傑爾．希欽（Nigel J Hitchin）1946年於英國 德比郡霍爾布魯克出生，現為英國牛津大學 Savilian幾何學講座教授，1968年於牛津大學 耶穌學院取得數學文學士學位，及1972年於牛 津大學沃爾夫森學院取得數學博士學位。他分 別在美國普林斯頓高等研究院擔任研究助理 （1971–1973）和紐約大學擔任高朗研究所導師 （1973–1974）。之後他回到牛津大學沃爾夫森 學院擔任初級研究員（1974–1977）和研究員 （1977–1979）。於1979年他成為牛津大學聖 凱瑟琳學院的數學導師及於1990年被委任為英 國華威大學教授。他曾任英國劍橋大學勞斯玻 爾數學講座教授（1994–1997），自1997年 起，他返回牛津大學任職Savilian幾何學講座 教授。他是英國倫敦皇家學會院士。
Nigel Hitchin was born in 1946 in Holbrook, Derbyshire, UK and is currently the Savilian Professor of Geometry at the University of Oxford, UK. He obtained his Bachelor of Arts in Mathematics from Jesus College, Oxford University in 1968 and his PhD in Mathematics from Wolfson College, Oxford University in 1972. He was a Research Assistant at the Institute for Advanced Study, Princeton, USA (1971–1973) and a Courant Institute Instructor in New York University (1973–1974). He returned to Oxford University in 1974 and served as a Junior Research Fellow (1974–1977) and Research Fellow (1977–1979) at Wolfson College. He became Tutor in Mathematics at St. Catherine's College, Oxford University in 1979 and was appointed Professor at the University of Warwick in 1990. He served as the Rouse Ball Professor of Mathematics at the University of Cambridge (1994–1997) and then returned to Oxford University serving as the Savilian Professor of Geometry since 1997. He is a Fellow of the Royal Society of London.
SHAW16-10-MATH 奈傑爾．希欽的貢獻 Contributions of Nigel J Hitchin
奈傑爾．希欽是近代最有影響力的幾何學家之一。他的研究工作為幾何學及與其相關的數學和物理學範疇帶來深 遠的影響。他多次發現幾何學中優美又自然的特點，這些特點至為關鍵，並激發了數學和物理學領域的研究工 作，扮演着重要的角色。通過探索幾何學中被忽略了的隅角，希欽曾多次發現未知的部分，改變了幾何學和相關 領域的發展，並影響了數學家們對這些問題的思考。
幾何學與數學的其他部分有着密不可分的聯繫，包括與研究對稱有關的表示論、微分方程與動力學、數論，並對 拓樸學有深遠的影響。長久以來它亦與物理學緊密連繫：愛因斯坦就是基於黎曼幾何並引入四維彎曲時空概念而 提出廣義相對論。近期經常談及的粒子物理學標準模型就是以規範理論的幾何學所制定，而許多標準模型以外的 理論高能物理都是按幾何學原理制定。
Nigel Hitchin is one of the most influential geometers of our time. The impact of his work on geometry and on many of the allied areas of mathematics and physics is deep and lasting. On numerous occasions, he has discovered elegant and natural facets of geometry that have proven to be of central importance. His ideas have turned out to be crucial in areas of mathematics and physics far removed from the context in which he first developed them. By exploring ignored corners of geometry, Hitchin has repeatedly uncovered the unknowns that have changed the course of developments in geometry and related areas, and changed the way mathematicians think about these subjects.
Geometry has close connections to other parts of mathematics such as representation theory, which is related to the study of symmetry, differential equations and dynamics, and number theory. It has had a profound impact on topology. Its connections to physics are long-standing as well: Einstein formulated general relativity in terms of the geometry of curved four-dimensional spacetime, essentially in the form that Riemann had introduced. More recently, the standard model of particle physics is formulated using the geometry of gauge theories, and much of theoretical high-energy physics beyond the standard model is formulated geometrically.
SHAW16-11-MATH 希欽的工作 - 希格斯叢和希欽纖維化 Work of Hitchin – Higgs Bundles and Hitchin Fibration
希欽在幾何學上提出了很多重要的概念和技術，當中最具影響力之一就是黎曼曲面上的希格斯叢的研究。
所有在固定曲面上的希格斯叢之參數空間就是在該曲面上的纖維叢。希欽在這些纖維叢上提出的自然函數能在該 空間產生一個在代數上完全可積的哈密頓系統，這就是在希格斯叢空間上的希欽纖維化，而這些空間能為超凱勒 流形提供基本的實例。但希欽纖維化的影響不僅限於希格斯叢和超凱勒流形，希欽纖維化和其量子化更是建構表 示論中一個重要現代分支 —「幾何朗蘭茲計劃」的基石。此外，最近吳寶珠獲頒菲爾茲獎，在其相關的自守形式 與數論工作中，希欽纖維化亦是其中的一個基本要素。
While Hitchin has introduced many important concepts and techniques in geometry, one of his most influential works is his study of Higgs bundles over a Riemann surface.
The parameter space of all Higgs bundles over a fixed surface is itself a fibre bundle over that surface. On these fibre bundles Hitchin defined a natural function that produces an algebraically completely integrable Hamiltonian system on the space. The result is what is now called the Hitchin fibration of the space of Higgs bundles. One aspect of these spaces is that they give fundamental examples of important objects known as hyperkahler manifolds. But the impact of Hitchin fibrations is not limited to Higgs bundles and hyperkahler manifolds. Hitchin fibrations and his quantisation of them are cornerstones of the construction of a modern branch of representation theory called 'the geometric Langlands programme'. In addition, they are a foundational ingredient in Ngo's recent Fields-Medal-winning work in the theory of automorphic forms and number theory.
希欽對相關科目研究的影響 Hitchin's Impact on Allied Subjects
希欽運用希欽纖維化於黎曼曲面的模空間上，構造出射影平坦聯絡，證實了威滕在分析陳-西蒙斯理論，即三維拓 撲量子場論時所作的預測。希欽纖維化開啟了物理學家對四維及六維量子場論的研究的大門，它亦是一個上佳例 證彰顯出希欽找尋具吸引力和自然的問題的能力，而這些問題往往於數學和物理學上具有根本的重要性但卻一直 被忽略。
希欽的工作對幾何學及與其相關的科目的應用帶來了深遠的影響。憑藉其多項卓越的成就讓他獲得邵逸夫數學科 學獎，獲獎是實至名歸。
Hitchin used Hitchin fibrations to construct projectively flat connections over the moduli spaces of Riemann surfaces, which had been predicted by Witten's analysis of Chern-Simons theory, a three-dimensional topological quantum field theory. Hitchin fibrations have also served as a point of departure for physicists in their studies of certain four- and six-dimensional quantum field theories. The story of Hitchin fibrations is a perfect example of Hitchin's ability to find appealing and natural questions that had been previously overlooked but whose answers are of fundamental importance across a wide spectrum of mathematics and physics.
The influence of Hitchin's work across the wide sweep of geometry and its applications to allied fields will be felt far into the future. His many achievements richly merit the award of the Shaw Prize in Mathematical Sciences.
SHAW16-12-MATH