Time filter

Source Type

Polishchuk E.V.,Telethon Institute of Genetics and Medicine | Concilli M.,Telethon Institute of Genetics and Medicine | Iacobacci S.,Telethon Institute of Genetics and Medicine | Chesi G.,Telethon Institute of Genetics and Medicine | And 25 more authors.
Developmental Cell | Year: 2014

Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease. © 2014 The Authors.


News Article | December 22, 2016
Site: www.eurekalert.org

An international team of scientists has discovered that the gene, OGDHL, a key protein required for normal function of the mitochondria -- the energy-producing factory of the cell -- and its chaperone, nardilysin (NRD1) are linked to progressive loss of neurological function in humans. Working with the fruit fly, an experimental animal model in the lab, the scientists found a mechanism by which misregulation of mitochondrial function leads to neurodegeneration. The results appear in Neuron. "In our research we look for genes whose loss of function results in deterioration of neurological functions in the fruit fly Drosophila melanogaster," said first author Dr. Wan Hee Yoon, postdoctoral fellow in the laboratory of Dr. Hugo Bellen, professor at Baylor College of Medicine, investigator at the Howard Hughes Medical Institute, and senior author of the paper. "In the fly we found that loss of function of nardilysinled to a slow, progressive neurodegeneration." Yoon and colleagues discovered that nardilysin helps the folding of an important protein, an enzyme called OGDH, present in mitochondria. Loss of nardilysin function results in loss of OGDH and a build-up of a compound called a-ketoglutarate (a-KG). High levels of a-KG increase a cellular response mechanism called mTOR that normally provides clearance of cellular components such as proteins and organelles. Yoon observed that mutation of nardilysin leads to abnormal build-up of a-KG followed by mTOR activation and eventually to slow accumulation of cellular trash. Importantly, a drug named rapamycin suppresses the neurodegenerative conditions caused by this accumulation of cellular garbage. In 2009, a group led by Dr. Eiichiro Nishi in Japan genetically engineered a mouse to lack nardilysin.The mice developed neurological problems with motor coordination, balance and memory issues, findings which at the time were not known to be linked to the mechanism described above in the fruit fly. The team led by Bellen realized that the results in fruit flies and in mice might suggest a role for nardilysin and its target protein OGDH in neurological problems in humans. At the same time that Yoon was investigating nardilysinand its target protein OGDH, across the street co-author Dr. Ender Karaca, a postdoctoral fellow in the laboratory of Dr. James R. Lupski's group at Baylor, was working to solve a rare disease by sequencing the patient's genome through the Baylor-Hopkins Center for Mendelian Genomics (BHCMG). Karaca had discovered a 16-year-old patient with a rare variant in OGDHL who was unable to walk, was bound to a wheelchair and whose head had not grown normally. Yoon and Karaca connected and realized that the mechanism in flies that Yoon was working on might explain the undiagnosed patient of Karaca. "We realized that Ender had identified OGDHL as the top candidate gene for his patient at the same time that we were identifying OGDHL as a target of nardilysin," said Yoon. "After we saw a patient with a severe disorder and variants in OGDHL, we wondered about nardilysin," said Bellen. The researchers then widened their search for similar patients by posting the information of the disease-causing variants of nardilysinin GeneMatcher, a web tool for rare disease researchers developed by the BHCMG team at Johns Hopkins University. Researchers looking for patients carrying rare disease genes post the gene in GeneMatcher. If another researcher around the world has a patient with a matching gene, the teams can contact each other to share the information and collaborate. By posting nardilysinin GeneMatcher, Yoon and colleagues identified a patient whose DNA had been sequenced at the University of California in Los Angeles Clinical Genomics Center. The patient is a 15-year-old boy who presents with symptoms that are remarkably similar to those present in the patient identified by Karaca. "We knew then that these two patients had a very similar disorder, but we had to prove that the genetic variants were causing their conditions," said Yoon and Bellen. Using flies to study how human disease genes work The data from the two patients were strong evidence that the variants in nardilysin and OGDHL are linked to neurodegenerative disease in humans. However, to establish that the disease variants can cause the condition, the researchers turned back to the flies where they could use genetic technology to test the variants. "We can test a human gene side by side with a copy containing a variant from a patient in flies," said co-author Dr. Michael F. Wangler, assistant professor of molecular and human genetics at Baylor. Using this technology, Yoon showed that mutant flies carrying a normal copy of the human gene show normal development and neuronal function. However, flies carrying genes with deleterious variants found in patients failed to rescue the loss of the genes in flies. This suggests that the mutations found in patients are indeed deleterious. "These studies show how valuable the fruit fly model is to uncover and test genes linked to human conditions, and to work out how mutations may cause diseases," said Bellen. Other contributors to this work include Hector Sandoval, Sonal Nagarkar-Jaiswal, Manish Jaiswal, Shinya Yamamoto, Nele A. Haelterman, Nagireddy Putluri, Vasanta Putluri, Arun Sreekumar, Tulay Tos, Ayse Aksoy, Taraka Donti, Brett H. Graham, Mikiko Ohno, Eiichiro Nishi, Jill Hunter, Donna M. Muzny, Jason Carmichael, Joseph Shen, Valerie A. Arboleda, Stanley F. Nelson. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children's Hospital, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases (Turkey), Kyoto University, Valley Children's Hospital at Madera and the University of California at Los Angeles. This study was supported by grants from the National Institutes of Health (NIH R01GM067858, NIH T32 NS043124-11) and the Research Education and Career Horizon Institutional Research and Academic Career Development Award Fellowship 5K12GM084897, the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, the CPRIT Metabolomics Core Facility Support Award RP120092, NCI/ 2P30CA125123-09 Shared Resources Metabolomics core, Dan L. Duncan Comprehensive Cancer Center (DLDCC), Alkek Center for Molecular Discovery, Mass Spectrometry COE by Agilent and the NIH R01GM098387. Further support came from research grants 26293068, 26670139 and 26116715 and a research program of the P-Direct from the MEXT of Japan and the NIH K08NS076547 funded by National Institute of Neurological Disorders and Stroke. The authors acknowledge the support of the NIH (1RC4GM096355), the Robert A. and Renee E. Belfer Family Foundation, the Huffington Foundation and Target ALS and the Howard Hughes Medical Institute. This work was also supported in part by a grant from the National institute of Neurological Disease and Stroke (R01NS058529), the Baylor-Hopkins Center for Mendelian Genomics, the US National Human Genome Research Institute, National Heart Lung and Blood Institute grant U54HG006542. J.R.L. has stock ownership in 23andMe and Lasergen, is a paid consultant for Regeneron Pharmaceuticals and is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases and bacterial genomic fingerprinting. The Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Baylor Genetics Laboratory.


Le Breakthrough Prize in Life Sciences 2017 est décerné à Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi et Huda Yahya Zoghbi Le Breakthrough Prize in Fundamental Physics 2017 est décerné à Joseph Polchinski, Andrew Strominger et Cumrun Vafa Le Breakthrough Prize in Mathematics 2017 est décerné à Jean Bourgain Le prix New Horizons in Physics est décerné à Asimina Arvanitaki, Peter W. Graham et Surjeet Rajendran ; Simone Giombi et Xi Yin ; et Frans Pretorius Le prix New Horizons in Mathematics est décerné à Mohammad Abouzaid, Hugo Duminil-Copin, et Benjamin Elias et Geordie Williamson Le deuxième Breakthrough Junior Challenge annuel est remporté par les étudiantes Antonella Masini, 18 ans (Pérou) et Deanna See, 17 ans (Singapour) Le Special Breakthrough Prize in Fundamental Physics 2016 a été décerné en mai aux fondateurs et aux membres de l'équipe de LIGO, et attribué à Kip Thorne, Rainer Weiss et à la famille de Ronald Drever Les lauréats seront récompensés lors d'un brillant gala de remise des prix présenté par Morgan Freeman, qui verra un spectacle en direct d'Alicia Keys et des interventions de Daniel Ek (PDG de Spotify), Jeremy Irons, Mark et Scott Kelly, Hiroshi Mikitani (PDG de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (PDG de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (PDG deYouTube) et des fondateurs des Breakthrough Prize SAN FRANCISCO, 5 décembre 2016 /PRNewswire/ -- Le Breakthrough Prize et ses fondateurs Sergey Brin et Anne Wojcicki, Yuri et Julia Milner, Mark Zuckerberg et Priscilla Chan, ont annoncé ce soir les lauréats des Breakthrough Prizes 2017, qui marquent le cinquième anniversaire de cette organisation reconnaissant les meilleures réussites en sciences de la vie, physique fondamentale et mathématiques. Ce sont au total 25 millions de dollars qui ont été décernés lors de la cérémonie de gala qui a eu lieu dans la Silicon Valley et a été présentée par Morgan Freeman. Chaque Breakthrough Prize représente un montant de 3 millions de dollars, ce qui en fait la récompense monétaire individuelle la plus élevée dans le domaine de la science. Cette année, un total de sept prix a été décerné à neuf personnes, alors que le Special Breakthrough Prize in Fundamental Physics, d'une valeur de 3 millions de dollars, a été divisé entre les trois fondateurs et les quelque mille membres de l'équipe de LIGO. Par ailleurs, trois prix New Horizons in Physics d'un montant de 100 000 USD ont été décernés à six physiciens en début de carrière, et trois autres prix New Horizons in Mathematics de 100 000 dollars ont été attribués à quatre jeunes mathématiciens. Et cette année il y a eu deux gagnantes du Breakthrough Junior Challenge, et chaque lauréate a reçu jusqu'à 400 000 dollars en prix destiné à la formation, pour elles-mêmes, pour leur professeur respectif et leur école. Depuis sa création en 2012, le Breakthrough Prize a attribué près de 200 millions de dollars pour récompenser des recherches qui bousculent les paradigmes de la physique fondamentale, des sciences de la vie et des mathématiques. « Il n'y a jamais eu d'époque plus importante pour soutenir les sciences », a déclaré le fondateur de Facebook, Mark Zuckerberg. « Les lauréats du Breakthrough Prize 2017 représentent les leaders de la recherche scientifique en physique, mathématiques et sciences de la vie. Leurs avancées vont ouvrir de nouvelles possibilités et contribuer à faire du monde un endroit meilleur pour tout le monde. » Le Breakthrough Prize in Life Sciences 2017 a été décerné à Stephen J. Elledge (École de médecine de Harvard) ; Harry F. Noller (Université de Californie, Santa Cruz) ; Roeland Nusse (Université Stanford) ; Yoshinori Ohsumi (Institut de Technologie de Tokyo) ; Huda Yahya Zoghbi (Baylor College of Medicine). Le Breakthrough Prize in Fundamental Physics 2017 a été décerné à Joseph Polchinski (Université de Californie, Santa Barbara) ; Andrew Strominger (Université de Harvard) et Cumrun Vafa (Université de Harvard). Les trois lauréats ont rejoint ceux du Special Prize in Fundamental Physics précédemment annoncé et attribué en mai 2016. Ronald Drever (Institut de Technologie de Californie, Pasadena), Kip Thorne (Institut de Technologie de Californie, Pasadena) et Rainer Weiss (Institut de technologie du Massachusetts) ont été reconnus en mai pour leur détection des vagues gravitationnelles, ce qui ouvre de nouveaux horizons en astronomie et en physique. Les trois gagnants du Prix spécial se partageront un montant d'un million de dollars, et les 1 012 membres de l'équipe de LIGO se partageront 2 millions de dollars. Le Breakthrough Prize in Mathematics 2017 a été décerné à Jean Bourgain (Institute for Advanced Study). La cérémonie de cette année marquera le cinquième anniversaire de l'organisation, et les lauréats seront sur le devant de la scène ce soir lors d'un gala exclusif organisé conjointement par les fondateurs Sergey Brin et Anne Wojcicki, Yuri et Julia Milner, Mark Zuckerberg et Priscilla Chan, et par le rédacteur en chef de Vanity Fair, Graydon Carter. L'acteur qui a remporté un Award® de l'Académie, Morgan Freeman, présentera le gala, qui verra un spectacle de l'actrice quinze fois primée par les Grammy Award®, Alicia Keys, et les interventions de personnalités comme Jeremy Irons, Mark et Scott Kelly, Hiroshi Mikitani (PDG de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (PDG de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (PDG de YouTube), ainsi que des fondateurs du Breakthrough Prize. La soirée sera placée sous le thème de « la portée universelle des idées ». « La science est universelle », a déclaré Yuri Milner. « Ce soir elle a rassemblé certains des plus grands acteurs, sportifs, musiciens, universitaires, entrepreneurs, astronautes et, bien entendu, scientifiques du monde entier, pour célébrer ce que l'esprit humain est capable de faire. Et cela a attiré un public venu des quatre points de la planète. » L'un des moments forts sera les discours prononcés par les deux étudiantes qui ont remporté le Breakthrough Junior Challenge, Antonella Masini, 18 ans (Pérou) et Deanna See, 17 ans (Singapour). Le Breakthrough Junior Challenge est un concours mondial de vidéos scientifiques conçu pour inspirer la pensée créative sur les concepts fondamentaux en sciences de la vie, physique ou mathématiques. En reconnaissance de leurs candidatures gagnantes, les deux étudiantes ont reçu jusqu'à 400 000 dollars en prix pour la formation, dont une bourse d'une valeur de 250 000 dollars, 50 000 dollars pour les professeurs qui les ont respectivement inspirées, ainsi qu'un laboratoire de pointe évalué à 100 000 dollars. Des candidatures venant de 146 pays ont été reçues pour l'édition 2016 du concours mondial, qui a démarré le 1er septembre 2016. Le Breakthrough Junior Challenge a été fondé par Mark Zuckerberg et Priscilla Chan, Yuri et Julia Milner, à travers la Breakthrough Prize Foundation, et se fonde sur une bourse provenant du fonds de Mark Zuckerberg à la Silicon Valley Community Foundation, et sur une bourse de Milner Global Foundation. « Le Breakthrough Junior Challenge encourage les étudiants à mieux comprendre les mondes des sciences et des mathématiques et à trouver du plaisir à les explorer », a déclaré la cofondatrice du Breakthrough Prize, la Dr Priscilla Chan. « Antonella et Deanna ont toutes les deux un brillant avenir dans les sciences et je suis ravie de récompenser leur travail. Ce sont aussi de grandes oratrices, dont les capacités à exprimer ces idées complexes d'une façon accessible et captivante est une vraie source d'inspiration. J'ai vraiment hâte de voir comment elles vont changer le monde. » Par ailleurs, six prix New Horizons – un prix annuel doté de de 100 000 dollars, qui reconnait les réussites de physiciens et de mathématiciens en début de carrière, ont été attribués. Le prix New Horizons in Physics a été décerné à : Le prix New Horizons in Mathematics a été décerné à : La cérémonie sera réalisée et produite, pour la quatrième fois, par Don Mischer, aux côtés des producteurs exécutifs Charlie Haykel et Juliane Hare de Don Mischer Productions. La cérémonie sera intégralement diffusée en direct sur NATIONAL GEOGRAPHIC à 10 h, heure de l'Est américain et 9 h, heure du centre, le dimanche 4 décembre. Un montage d'une heure de la cérémonie sera également retransmis sur FOX le dimanche 18 décembre, à 19 heures, heure de l'Est et 20 heures, heure du Pacifique, et à l'échelle mondiale sur NATIONAL GEOGRAPHIC dans 171 pays et en 45 langues. Le Breakthrough Prize in Life Sciences récompense des avancées qui transforment la compréhension des systèmes vivants et de l'extension de la vie humaine, avec un prix consacré au travail contribuant à la compréhension des maladies neurologiques. Chacun des cinq lauréats des prix de Sciences de la vie a reçu une récompense de 3 millions de dollars. Stephen J. Elledge, professeur de génétique et de médecine, titulaire de la chaire Gregor Mendel, au département de génétique à l'École de médecine de Harvard et de la division de génétique au Brigham and Women's Hospital et chercheur au Howard Hughes Medical Institute, pour expliciter la façon dont les cellules eucaryotes sentent et répondent aux dommages faits dans leur ADN et pour donner des informations sur le développement et le traitement du cancer. Harry F. Noller, directeur du Center for Molecular Biology of RNA (Centre de la biologie moléculaire de l'ARN), Robert L. Sinsheimer, professeur de biologie moléculaire et professeur émérite de biologie moléculaire, cellulaire et du développement à l'Université de Californie, Santa Cruz, pour avoir découvert le rôle central de l'ARN dans la formation des centres actifs du ribosome, la machinerie fondamentale de la synthèse des protéines dans toutes les cellules, connectant ainsi la biologie moderne à l'origine de la vie et expliquant également combien d'antibiotiques naturels perturbent la synthèse des protéines. Roeland Nusse, professeur de biologie du développement à l'université Stanford et chercheur au Howard Hughes Medical Institute, pour sa recherche pionnière sur la voie des protéines Wnt, l'un des systèmes de signalement intercellulaire fondamentaux dans le développement, le cancer et la biologie des cellules souche. Yoshinori Ohsumi, professeur honoraire, Institut de la recherche innovante de l'Institut de technologie de Tokyo pour élucider l'autophagie, le système de recyclage que les cellules utilisent pour générer des substances nutritives provenant de leurs composants non essentiels ou endommagés. Huda Yahya Zoghbi, professeur du département de pédiatrie, de génétique moléculaire et humaine, de neurologie et de neurosciences au Baylor College of Medicine, chercheur au Howard Hughes Medical Institute et directeur du Jan and Dan Duncan Neurological Research Institute (NRI) à l'Hôpital pour enfants du Texas, pour ses découvertes sur les causes génétiques et les mécanismes biochimiques de l'ataxie spinocérébelleuse et du syndrome de Rett, découvertes qui ont ouvert des fenêtres sur la pathogénèse des maladies neurodégénératives et neurologiques. Le Breakthrough Prize in Fundamental Physics reconnait les plus grandes idées sur les questions les plus profondes que nous pose l'univers. Les trois gagnants, qui se partagent un prix de 3 millions de dollars, sont : Joseph Polchinski, professeur au département de physique et membre du Kavli Institute for Theoretical Physics à l'Université de Californie, Santa Barbara ; Andrew Strominger, directeur du Center for the Fundamental Laws of Nature de l'université Harvard ; et, Cumrun Vafa, professeur de sciences, titulaire de la chaire Donner, au département de physique de l'université Harvard. Tous les trois ont reçu le prix pour les avancées transformatrices en théorie quantique des champs, théorie des cordes et gravité quantique. Le Breakthrough Prize in Mathematics récompense les meilleurs mathématiciens au monde qui ont contribué à des avancées majeures dans ce domaine. Jean Bourgain, professeur de mathématiques, titulaire de la chaire IBM von Neumann, à l'École de mathématiques de l'Institute for Advanced Study, Princeton, New Jersey, pour ses multiples contributions qui transforment l'analyse, la combinatoire, les équations différentielles partielles, la géométrie hautement dimensionnelle et la théorie des numéros. Le New Horizons in Physics Prize est décerné à de prometteurs chercheurs en début de carrière qui ont déjà produit un travail important en physique fondamentale. Le prix New Horizons in Mathematics est décerné à de prometteurs chercheurs en début de carrière qui ont déjà produit un travail important en mathématiques. Le deuxième Breakthrough Junior Challenge annuel reconnaît deux vainqueurs cette année - Antonella Masini, 18 ans, du Pérou, et Deanna See, 17 ans, de Singapour. Antonella et Deanna recevront chacune jusqu'à 400 000 dollars en prix pour la formation. La vidéo d'Antonella, présentée dans la catégorie « physique », est axée sur l'intrication quantique. La vidéo de sciences de la vie de Deanna, intitulée « Superbugs! And Our Race against Resistance » (Superbactéries ! Et notre course contre la résistance) abordait la résistance aux antibiotiques. Les images et les vidéos choisies du gala du Breakthrough Prize 2017 – tapis rouge et cérémonie – peuvent être téléchargées à des fins d'utilisation par la presse sur : Pour la cinquième année consécutive, les Breakthrough Prizes vont reconnaître les meilleurs scientifiques au monde. Chaque prix a une valeur de 3 millions de dollars et récompense dans les domaines des sciences de la vie (jusqu'à cinq prix par an), de la physique fondamentale (un prix par an) et des mathématiques (un prix par an). Par ailleurs, jusqu'à trois prix New Horizons in Physics et jusqu'à trois prix New Horizons in Mathematics sont décernés à de jeunes chercheurs chaque année. Les lauréats participent à une cérémonie de remise des prix télévisée conçue pour célébrer leurs réussites et pour inspirer la nouvelle génération de scientifiques. Dans le cadre de l'agenda de la cérémonie, ils participent aussi à un programme de conférences et de débats. Les Breakthrough Prizes ont été fondés par Sergey Brin et Anne Wojcicki, Mark Zuckerberg et Priscilla Chan, Yuri et Julia Milner. Des comités de sélection composés de précédents lauréats du Breakthrough Prize choisissent les vainqueurs. Vous trouverez des informations sur les Breakthrough Prizes en cliquant sur www.breakthroughprize.org.


-       Breakthrough Prize celebra su 5 aniversario con los principales logros en ciencias y otorga premios por 25 millones de dólares en una ceremonia de gala celebrada en Silicon Valley New Horizons in Physics Prize otorgado a Asimina Arvanitaki, Peter W. Graham y Surjeet Rajendran; Simone Giombi y Xi Yin y Frans Pretorius New Horizons in Mathematics Prize otorgado a Mohammad Abouzaid, Hugo Duminil-Copin y Benjamin Elias y Geordie Williamson La segunda edición anual del International Breakthrough Junior Challenge se ha otorgado a las estudiantes femeninas Antonella Masini, 18 (Perú) y Deanna See, 17 (Singapur) 2016 Special Breakthrough Prize in Fundamental Physics, otorgado en mayo a los fundadores y miembros del equipo de LIGO, otorgado a Kip Thorne, Rainer Weiss y la familia de Ronald Drever Los premiados serán galardonados en la resplandeciente gala de premios hospedada por medio Morgan Freeman, con actuaciones en directo de Alicia Keys y presentaciones a cabo de Daniel Ek (consejero delegado de Spotify), Jeremy Irons, Mark y Scott Kelly, Hiroshi Mikitani (consejero delegado de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (consejero delegado de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (consejera delegada de YouTube) y los fundadores del Breakthrough Prize SAN FRANCISCO, 9 de diciembre de 2016 /PRNewswire/ -- El Breakthrough Prize y los fundadores Sergey Brin y Anne Wojcicki, Yuri y Julia Milner, y Mark Zuckerberg y Priscilla Chan, anunciaron anoche a los receptores de los 2017 Breakthrough Prizes, marcando así el 5 aniversario de la organización que reconoce los logros principales en Ciencias de la Vida, Física Fundamental y Matemáticas. Una cifra combinada total de 25 millones de dólares se otorgó en la ceremonia de gala en Silicon Valley, hospedada por medio de Morgan Freeman. Cada uno de los Breakthrough Prizes tiene un valor de 3 millones de dólares, el premio en metálico individual más grande dentro de la ciencia. Este año, se han otorgado un total de siete premios a nueve personas, junto con un Special Breakthrough Prize in Fundamental Physics de 3 millones de dólares, que se dividió entre los tres fundadores y más de 1.000 miembros del equipo LIGO. Además, se otorgaron tres New Horizons in Physics Prizes de 100.000 dólares para seis físicos en sus inicios de carrera, y otros tres New Horizons in Mathematics Prizes de 100.000 dólares otorgados a cuatro jóvenes matemáticos. Y este año, hubo dos ganadores del Breakthrough Junior Challenge, recibiendo cada uno de ellos hasta 400.000 dólares en premios de formación para ellos, su profesor y su escuela. Desde su creación en el año 2012, el Breakthrough Prize ha otorgado cerca de 200 millones de dólares para honrar el avance de la investigación del paradigma en los campos de la física fundamental, ciencias de la vida y matemáticas. "Nunca ha habido un momento más importante en el que apoyar la ciencia", destacó el fundador de Facebook, Mark Zuckerberg. "Los premiados con el 2017 Breakthrough Prize representan a los líderes en los campos de la investigación científica en física, matemáticas y ciencias de la vida. Sus descubrimientos desvelarán nuevas posibilidades y ayudarán a conseguir que el mundo sea un lugar mejor para todos". El 2017 Breakthrough Prize in Life Sciences fue otorgado a Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Tokyo Institute of Technology); Huda Yahya Zoghbi (Baylor College of Medicine). El 2017 Breakthrough Prize in Fundamental Physics fue otorgado a Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University) y Cumrun Vafa (Harvard University). Los tres premiados se unieron a los receptores del Special Prize in Fundamental Physics anunciados anteriormente, lanzado en mayo de 2016. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) y Rainer Weiss (Massachusetts Institute of Technology), fueron reconocidos en mayo por su detección de las olas gravitacionales, abriendo con ello nuevos horizontes en astronomía y física. Los tres ganadores del Special Prize compartirán un premio de 1 millón de dólares, y los 1.012 miembros del equipo LIGO compartirán 2 millones de dólares. El 2017 Breakthrough Prize in Mathematics fue otorgado a Jean Bourgain (Institute for Advanced Study). La ceremonia de este año marcará el 5 aniversario de la organización, y los premiados tomarán el escenario esta noche durante una gala exclusiva celebrada de forma conjunta con los fundadores Sergey Brin y Anne Wojcicki, Yuri y Julia Milner, Mark Zuckerberg y Priscilla Chan, además del editor de Vanity Fair, Graydon Carter. El actor ganador del Academy Award®, Morgan Freeman, hospedará el show, que contará con la actuación de la ganadora de 15 Grammy Award®, Alicia Keys, y los famosos presetadores Jeremy Irons, Mark y Scott Kelly, Hiroshi Mikitani (consejero delegado de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (consejero delegado de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (consejera delegada de YouTube), además de los fundadores del Breakthrough Prize. El tema de la noche será "the universal reach of ideas". "La ciencia es universal", destacó Yuri Milner. "Esta noche ha reunido a algunos de los mejores actores, deportistas, músicos, académicos, empresarios, astronautas y finalmente pero no por ello menos importante, científicos, para celebrar lo que la mente humana puede conseguir. Y lo ha hecho por medio de un evento en directo emitido en todo el planeta". Uno de estos puntos álgidos serán los discursos de dos estudiantes femeninas que han ganado el Breakthrough Junior Challenge, Antonella Masini, 18 (Perú) y Deanna See, 17 (Singapur). El Breakthrough Junior Challenge es una competición de video de ciencias de nivel mundial diseñado para inspirar el pensamiento creativo acerca de los conceptos fundamentales en las ciencias de la vida, física o matemáticas. Como reconocimiento a sus envíos ganadores, ambas estudiantes recibieron hasta 400.000 dólares en premios de formación, incluyendo una beca con un valor de 250.000 dólares, 50.000 dólares para un profesor inspirador y un laboratorio de última tecnología valorado en 100.000 dólares. Las participaciones procedentes de 146 países fueron recibidas en la entrega de 2016 de la competición final, que se puso en marcha el 1 de septiembre de 2016. El Breakthrough Junior Challenge cuenta con los fondos Mark Zuckerberg y Priscilla Chan, y Yuri y Julia Milner, a través de la Breakthrough Prize Foundation, basándose en una beca del fondo de Mark Zuckerberg en la Silicon Valley Community Foundation, además de una beca de la Milner Global Foundation. "El Breakthrough Junior Challenge insta a los estudiantes a comprender mejor los mundos de la ciencia y las matemáticas y divertirse durante ese viaje", destacó la cofundadora del Breakthrough Prize, la doctora Priscilla Chan. "Antonella y Deanna cuentan ambas con un futuro brillante en ciencias, y estoy emocionada de honrar su trabajo. Se trata además de dos increíbles contadoras de historias, cuya capacidad para capturar estas ideas complejas de forma accesible y emocionante es realmente inspiradora. No encuentro el momento de ver cómo van a cambiar el mundo". Además, se han otorgado seis premios New Horizons – un premio anual de 100.000 dólares cada uno, que reconocen los logros de los médicos de carrera primaria y matemáticos. El New Horizons in Physics Prize fue otorgado a: El New Horizons in Mathematics Prize fue otorgado a: La ceremonia estará dirigida y producida, por cuarta ocasión, por medio de Don Mischer junto a los productores ejecutivos Charlie Haykel y Juliane Hare de Don Mischer Productions. La emisión en directo corre a cargo de NATIONAL GEOGRAPHIC a las 10/9c del domingo 4 de diciembre, con una versión editada de una hora de la ceremonia emitida además por medio de FOX el domingo 18 de diciembre a las 7:00-8:00 PM ET/PT y a nivel mundial en NATIONAL GEOGRAPHIC en 171 países y 45 idiomas. El Breakthrough Prize in Life Sciences honora los avances transformadores hacia el conocimiento de los sistemas de vida y ampliación de la vida humana, con un premio dedicado al trabajo que contribuye al conocimiento de cara a las enfermedades neurológicas. Cada uno de los cinco ganadores de Life Science recibió un premio de 3 millones de dólares. Stephen J. Elledge, profesor Gregor Mendel de Genética y Medicina del Departamento de Genética de la Harvard Medical School y de la División de Genética del Brigham and Women's Hospital e investigador del Howard Hughes Medical Institute, por esclarecer cómo las células eucariotas sienten y responden a los daños en su ADN y proporcionar visiones sobre el desarrollo y tratamiento del cáncer. Harry F. Noller, director del Center for Molecular Biology of RNA, profesor Robert L. Sinsheimer de Biología Molecular y Profesor Emérito de Biología MCD de la University of California, Santa Cruz, por descubrir la centralidad del ARN en la formación de centros activos del ribosoma, la maquinaria fundamental de síntesis de proteína en todas las células, conectando con ello la biología moderna al origen de la vida y explicando además cómo muchos de los antibióticos naturales interrumpen la síntesis de proteínas. Roeland Nusse, profesor de Biología de Desarrollo de la Stanford University e investigador del Howard Hughes Medical Institute, por ser pionero en la investigación de la ruta Wnt, uno de los sistemas de señalización intercelular más importantes en la biología de desarrollo, cáncer y células madre. Yoshinori Ohsumi, profesor honorario del Institute of Innovative Research del Tokyo Institute of Technology por descubrir la autofagia, sistema de reciclaje que usan las células para generar nutrientes por sí mismas en componentes esenciales o dañados. Huda Yahya Zoghbi, profesor de los Departamentos de Pediatría, Molecular y genetic Humana, Neurología y Neurociencias del Baylor College of Medicine, investigador del Howard Hughes Medical Institute y director del Jan and Dan Duncan Neurological Research Institute (NRI) del Texas Children's Hospital, por sus descubrimientos de las causas genéticas y mecanismos bioquímicos de la ataxia espinocerebral y síndrome Rett, descubrimientos que han proporcionado visión dentro de la patogénesis de las enfermedades neurodegenerativas y neurológicas. El Breakthrough Prize in Fundamental Physics reconoce las mayores visiones dentro de las preguntas más profundas acerca del universo. Los tres ganadores, que comparten el premio de 3 millones de dólares, son: Joseph Polchinski, profesor del Departamento de Física y Miembro del Kavli Institute for Theoretical Physics de la University of California, Santa Bárbara; Andrew Strominger, director del Center for the Fundamental Laws of Nature de la Harvard University; y, Cumrun Vafa, profesor donner de Ciencias del Departamento de Física de la Harvard University, Los tres recibieron el premio por los avances transformadores en la teoría del campo cuántico, teoría de cuerdas y gravedad cuántica. El Breakthrough Prize in Mathematics honra a los mejores matemáticos del mundo, que han contribuido de cara a los avances más importantes en el campo. Jean Bourgain, profesor IBM von Neumann en la Escuela de Matemáticas del Institute for Advanced Study, Princeton, Nueva Jersey, por sus múltiples contribuciones de transformación para el análisis, combinatoria, ecuaciones diferenciales parciales, geometría de alta dimensión y teoría de números. El New Horizons in Physics Prize se otorga a los investigadores prometedores que empiezan sus carreras que yah an producido un trabajo importante en la física fundamental. El New Horizons in Mathematics Prize se concede a los investigadores prometedores en el principio de sus carreras que ya han producido importantes trabajos en matemáticas. La segunda edición anual del Breakthrough Junior Challenge reconoce a dos ganadores este año - Antonella Masini, 18, de Perú, y Deanna See, 17, de Singapur. Antonella y Deanna recibirán cada una hasta 400.000 dólares en premios de formación. El video de Antonella, enviado en la categoría de física, se centra en la implicación cuántica. El video de las ciencias de la vida de Deanna, titulado "Superbugs! And Our Race against Resistance", hace frente a la resistencia a los antibióticos. Las imágenes y video seleccionado de la 2017 Breakthrough Prize Gala – alfombra roja y ceremonia – se pueden descargar para su uso de medios a través de: Por quinto año, los premios Breakthrough Prize darán su reconocimiento a los mejores científicos del mundo. Cada premio tiene una dotación de 3 millones de dólares y se presenta en las áreas de Ciencias de la Vida (hasta cinco por año), Física Fundamental (máximo uno por año) y Matemáticas (máximo uno por año). Además, cada año se entregan hasta tres premios New Horizons de Física y hasta tres New Horizons de Matemáticas a jóvenes investigadores. Los ganadores asisten a una ceremonia de entrega de premios que se emite por televisor pensada para celebrar sus logros e inspirar a la nueva generación de científicos. Como parte de la programación de la ceremonia, también entran en un programa de ponencias y debates. Los premios al descubrimiento fueron fundados por Sergey Brin y Anne Wojcicki, Mark Zuckerberg y Priscilla Chan, y Yuri y Julia Milner. Los comités de selección están compuestos por ganadores anteriores de los premios Breakthrough Prize y quienes eligen a los ganadores. Información acerca de los Breakthrough Prizes disponible a través de www.breakthroughprize.org.


2017 Breakthrough Prize in Life Sciences an Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi und Huda Yahya Zoghbi verliehen 2017 Breakthrough Prize in Grundlagenphysik geht an Joseph Polchinski, Andrew Strominger und Cumrun Vafa New Horizons in Physics Prize an Asimina Arvanitaki, Peter W. Graham und Surjeet Rajendran; Simone Giombi und Xi Yin sowie Frans Pretorius verliehen New Horizons in Mathematics Prize geht an Mohammad Abouzaid, Hugo Duminil-Copin sowie Benjamin Elias und Geordie Williamson Zweiter jährlich verliehener International Breakthrough Junior Challenge von zwei Schülerinnen gewonnen Antonella Masini, 18 (Peru) und Deanna See, 17 (Singapur) Im Mai 2016 an Gründer und Teammitglieder von LIGO verliehener Special Breakthrough Prize in Grundlagenphysik an Kip Thorne, Rainer Weiss und die Familie von Ronald Drever überreicht Ehrung der Preisträger mit glanzvoller, von Morgan Freeman moderierter Awards Gala mit Live-Auftritt von Alicia Keys und Preisübergabe durch Daniel Ek (CEO von Spotify), Jeremy Irons, Mark und Scott Kelly, Hiroshi Mikitani (CEO von Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO von Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO von YouTube) und die Gründer des Breakthrough Prize. SAN FRANCISCO, 6. Dezember 2016 /PRNewswire/ -- Der Breakthrough Prize und seine Begründer Sergey Brin und Anne Wojcicki, Yuri und Julia Milner sowie Mark Zuckerberg und Priscilla Chan haben am heutigen Abend die Empfänger der Breakthrough Prizes 2017 bekanntgegeben. Dies steht zugleich für den fünften Jahrestag der Organisation, die Spitzenleistungen in den Biowissenschaften, der Grundlagenphysik und der Mathematik würdigt. Insgesamt wurden auf der von Morgan Freeman moderierten Gala-Veranstaltung in Silicon Valley 25 Millionen USD vergeben. Jeder der der Breakthrough Prizes ist mit einer Summe von 3 Millionen USD dotiert, der finanziell höchstdotierte Einzelpreis im Bereich der Wissenschaften. Diesjährig wurden, neben einem mit 3 Millionen USD dotierten, zwischen drei Gründern und mehr als tausend Mitgliedern des LIGO Team aufgeteilten Special Breakthrough Prize in Grundlagenphysik, insgesamt sieben Preise an neun Personen verliehen. Zusätzlich wurden drei mit 100.000 USD ausgeschriebene „New Horizons in Physics"-Preise an sechs Physiker, die am Anfang ihrer Karriere stehen und weitere drei mit 100.000 USD dotierte „New Horizons in Mathematics"-Preise an vier junge Mathematiker vergeben. In diesem Jahr gab es zwei Gewinner des Breakthrough Junior Challenge, die jeder jeweils bis zu 400.000 USD in Bildungspreisen für sich selbst, ihre Lehrer und ihre Schulen in Empfang nehmen konnten. Der im Jahre 2012 ins Leben gerufene Breakthrough Prize hat annähernd 200 Millionen USD vergeben, um einen Paradigmenwechsel in den Bereichen Grundlagenphysik, Biowissenschaften und Mathematik zu würdigen. „Die Wissenschaft zu unterstützen ist so wichtig wie nie zuvor", erklärte Facebook-Gründer Mark Zuckerberg. „Die Preisträger des 2017 Breakthrough Prize stehen für die führende wissenschaftliche Forschung in Physik, Mathematik und Life Sciences. Ihre bahnbrechenden Erkenntnisse werden neue Möglichkeiten erschließen und zu einer für uns alle besseren Welt beitragen". Der 2017 Breakthrough Prize in Life Sciences ging an Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Technische Hochschule Tokio); Huda Yahya Zoghbi (Baylor College of Medicine). Der 2017 Breakthrough Prize in Grundlagenphysik wurde an Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University); und Cumrun Vafa (Harvard University) verliehen. Die drei Preisträger konnten sich den bereits im Mai 2016 bekanntgegebenen Empfängern des Sonderpreises in Grundlagenphysik anschließen. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) und Rainer Weiss (Massachusetts Institute of Technology) waren im Mai für den Nachweis von Gravitationswellen ausgezeichnet worden, der neue Horizonte in der Astronomie und Physik eröffnet. Die drei Preisträger des Special Prize teilen sich eine 1 Million USD an Preisgeld, zwei Millionen gehen zu gleichen Teilen an 1012 Mitglieder des LIGO-Teams. Der 2017 Breakthrough Prize in Mathematik wurde an Jean Bourgain (Institute for Advanced Study) vergeben. Die diesjährige Zeremonie steht für das fünfte Jubiläum der Organisation. Die Preisträger werden heute Abend im Rahmen von den Gründern Sergey Brin und Anne Wojcicki, Yuri und Julia Milner, Mark Zuckerberg und Priscilla Chan sowie Vanity Fair-Herausgeber Graydon Carter mitausgerichteten einer exklusiven Gala auf der Bühne stehen. Schauspieler und Academy Award®-Gewinner Morgan Freeman wird als Gastgeber der Veranstaltung fungieren, in deren Rahmen es einen Auftritt der mit 15 Grammy Awards® ausgezeichneten Alicia Keys geben wird. Als prominente Preisverleiher treten Jeremy Irons, Mark und Scott Kelly, Hiroshi Mikitani (CEO von Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO von Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO von YouTube) sowie die Begründer des Breakthrough Prize in Erscheinung. Der Abend wird unter dem Motto „die universelle Reichweite von Ideen" stehen. „Wissenschaft ist universell", sagte Yuri Milner. „Sie hat heute Abend einige der weltweit größten Schauspieler, Sportler, Musiker, Akademiker, Entrepreneure, Astronauten und, nicht zu vergessen, Wissenschaftler, zusammengebracht, um zu feiern, was der menschliche Geist erreichen kann. Und sie macht möglich, dass hier ein planetenweites Live-Publikum mit dabei ist". Eines der Highlights sind die Reden der beiden Schülerinnen, die den Breakthrough Junior Challenge gewonnen haben, Antonella Masini, 18 (Peru) und Deanna See, 17 (Singapur). Der Breakthrough Junior Challenge ist ein globaler Videowettbewerb im Bereich der Wissenschaften, der zu kreativem Denken hinsichtlich Grundkonzepten in den Biowissenschaften, der Physik oder der Mathematik anregen soll. In Anerkennung ihrer siegreichen Einreichungen erhielten beide Schülerinnen bis zu 400.000 USD in Bildungspreisen einschließlich eines Stipendiums im Wert von bis zu 250.000 USD, 50.000 USD für einen inspirierenden Lehrer und ein wissenschaftliches Labor auf dem neuestem Stand der Technik im Wert von 100.000 USD. Für die 2016 Ausgabe des globalen Wettbewerbs gingen mit Starttermin zum 1. September 2016 Beiträge aus 146 Ländern ein. Der Breakthrough Junior Challenge wird von Mark Zuckerberg und Priscilla Chan sowie Yuri und Julia Milner über die Breakthrough Prize Foundation mit einer Förderung durch Mark Zuckerbergs Fonds in der Silicon Valley Community Foundation und finanzieller Unterstützung der Milner Global Foundation finanziert. „Der Breakthrough Junior Challenge ermutigt die Schüler, die Welten von Wissenschaft und Mathematik besser zu verstehen und Spaß daran zu haben", erklärte Breakthrough Prize Mitbegründerin Dr. Priscilla Chan. „Antonella und Deanna haben beide beste Zukunftsaussichten in der Welt der Wissenschaften, und ich bin hocherfreut, sie für ihre Arbeit derart würdigen zu können. Sie können darüber hinaus hervorragend Geschichten erzählen und besitzen eine Fähigkeit, diese komplexen Ideen zugänglich und aufregend zu erfassen und zu vermitteln, die wirklich inspirierend ist. Ich bin äußerst gespannt darauf, mitzuerleben, wie sie die Welt verändern werden". Zusätzlich wurden sechs New Horizons-Preise verliehen, eine jährlich vergebene und mit jeweils 100.000 USD dotierte Auszeichnung, die die Leistungen von Physikern und Mathematikern würdigen, die am Anfang ihrer Karriere stehen. Der New Horizons in Physics Prize ging an: Der New Horizons in Mathematics Prize ging an: Die Preisverleihung steht zum vierten Male unter der Leitung und Regie von Don Mischer, gemeinsam mit den ausführenden Produzenten Charlie Haykel und Juliane Hare von Don Mischer Productions. Die Gala wurde in vollem Umfang live auf NATIONAL GEOGRAPHIC am Sonntag, 4. Dezember um 22:00 Uhr/21:00 Uhr ET/CT übertragen. Eine auf eine Stunde editierte Version der Preisverleihung wird ebenfalls über FOX am Sonntag, 18. Dezember, von 19:00 Uhr - 20:00 Uhr ET/PT und global über NATIONAL GEOGRAPHIC in 171 Ländern und 45 Sprachen zu sehen sein. Der Breakthrough Prize in Life Sciences ehrt transformative Fortschritte zum Verständnis lebender Systeme und zur Verbesserung des menschlichen Lebens, wobei einer der Preise der Arbeit gewidmet ist, die zum Verständnis der neurologischen Erkrankungen beiträgt. Jeder der fünf Gewinner des Life Science-Preises hat 3 Millionen USD erhalten. Stephen J. Elledge, Gregor Mendel Professor für Genetik und Medizin in der Abteilung für Genetik an der Harvard Medical School und an der Abteilung für Genetik am Brigham and Women's Hospital und Investigator am Howard Hughes Medical Institute, für seine Darlegung, wie eukaryotische Zellen Schäden in ihrer DNA spüren und auf diese reagieren, und Erkenntnisse zur Entwicklung und Behandlung von Krebs. Harry F. Noller, Direktor des Zentrums für Molekularbiologie der RNA, Robert L. Sinsheimer Professor für Molekularbiologie und Professor Emeritus für MCD Biologie an der University of California, Santa Cruz, für die Entdeckung der zentralen Rolle, die RNA bei der Bildung der aktiven Zentren des Ribosoms zukommt, der grundlegenden Maschinerie der Proteinsynthese in allen Zellen, was die moderne Biologie mit dem Ursprung des Lebens verknüpft und auch erklärt, auf welche Weise viele natürliche Antibiotika die Proteinsynthese stören. Roeland Nusse, Professor für Entwicklungsbiologie an der Stanford University und Investigator am Howard Hughes Medical Institute, für Pionierforschung zum Wnt-Signalweg, eines der entscheidenden interzellulären Signalisierungssysteme in der Entwicklungs-, Krebs- und Stammzellbiologie. Yoshinori Ohsumi, Honorarprofessor am Institut für Innovative Forschung an der Technischen Hochschule Tokio, für die Darlegung der Autophagie, des Recycling-Systems, das Zellen verwenden, um Nährstoffe aus ihren eigenen unwesentlichen oder beschädigten Komponenten zu erzeugen. Huda Yahya Zoghbi, Professorin an den Abteilungen für Pädiatrie, Molekulare und Humangenetik, Neurologie und Neurowissenschaften am Baylor College of Medicine, Investigator am Howard Hughes Medical Institute und Direktorin des Jan and Dan Duncan Neurological Research Institute (NRI) am Texas Children's Hospital, für die Entdeckung der genetischen Ursachen und biochemischen Mechanismen der spinozerebellären Ataxie und des Rett-Syndroms, Erkenntnisse, die einen Einblick in die Pathogenese neurodegenerativer und neurologischer Erkrankungen gegeben haben. Der Breakthrough Prize in Fundamental Physics würdigt wichtige Erkenntnisse zu den tiefstgründigen Fragestellungen des Universums. Die drei Gewinner, die sich die Summe von 3 Millionen USD teilen, sind: Joseph Polchinski, Professor am Fachbereich für Physik und Mitglied des Kavli Institut für Theoretische Physik an der University of California, Santa Barbara; Andrew Strominger, Direktor des Center for the Fundamental Laws of Nature an der Harvard University; und, Cumrun Vafa, Donner Professor für Wissenschaft am Fachbereich für Physik an der Harvard University, Alle drei erhielten den Preis für transformative Fortschritte in der Quantenfeldtheorie, Stringtheorie und Quantengravitation. Der Breakthrough Prize in Mathematics ehrt die besten Mathematiker der Welt, die zu großen Fortschritten in diesem Bereich beigetragen haben. Jean Bourgain, IBM von Neumann Professor an der Fakultät für Mathematik am Institute for Advanced Study, Princeton, New Jersey, für mehrere transformative Beiträge zu Analyse, Kombinatorik, partiellen Differentialgleichungen, hochdimensionaler Geometrie und Zahlentheorie. Der New Horizons in Physics Prize wird vielversprechenden Forschern verliehen, die am Anfang ihrer Karriere stehen und bereits wichtige Arbeit in der Grundlagenphysik geleistet haben. The New Horizons in Mathematics Prize wird vielversprechenden Forschern verliehen, die am Anfang ihrer Karriere stehen und bereits wichtige Arbeit in der Mathematik geleistet haben. Der zweite, jährlich vergebene Breakthrough Junior Challenge würdigt in diesem Jahr zwei Gewinner - Antonella Masini, 18, aus Peru, und Deanna See, 17, aus Singapur. Antonella und Deanna erhalten jeweils bis zu 400.000 USD an Bildungspreisen. Das von Antonella in der Kategorie Physik eingereichte Video fokussiert sich auf Quantenverschränkung. Deannas Video für Life Sciences trägt den Titel „Superbugs! And Our Race against Resistance" (Superbugs! Unser Wettlauf mit der Resistenz) und beschäftigt sich mit Antibiotikaresistenz. Bilder und ausgewähltes Videomaterial der 2017 Breakthrough Prize Gala mit Begrüßung auf dem rotem Teppich und Preisverleihung können für Pressezwecke unter folgendem Link heruntergeladen werden: Die Breakthrough Prizes zeichnen mittlerweile im fünften Jahr die weltweit führenden Wissenschaftler aus. Jeder Preis ist mit einer Summe von 3 Millionen USD dotiert und wird für die Bereiche Life Sciences (bis zu fünf pro Jahr), Grundlagenphysik (ein Preis pro Jahr) und Mathematik (ein Preis pro Jahr) vergeben. Darüber hinaus werden jährlich bis zu drei „New Horizons"-Preise in Physik und bis zu drei „New Horizons"-Preise in Mathematik an vielversprechende junge Wissenschaftler verliehen. Die Preisträger nehmen an einer im Fernsehen übertragenen Award-Verleihung zur Anerkennung ihrer Verdienste teil, die auch die nächste Generation von Wissenschaftlern inspirieren soll. Im Rahmen der Feierlichkeit nehmen sie ebenfalls an einem Programm von Vorlesungen und Diskussionen teil. Begründer der Breakthrough Prizes waren Sergey Brin und Anne Wojcicki, Mark Zuckerberg und Priscilla Chan sowie Yuri und Julia Milner. Auswahlgremien, die sich aus früheren Preisträgern der Breakthrough Prizes zusammensetzen, wählen die Gewinner aus. Informationen über die Breakthrough Prizes erhalten Sie unter www.breakthroughprize.org.


2017 Breakthrough Prize in Life Sciences Awarded to Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi, and Huda Yahya Zoghbi 2017 Breakthrough Prize in Fundamental Physics Awarded to Joseph Polchinski, Andrew Strominger, and Cumrun Vafa New Horizons in Physics Prize awarded to Asimina Arvanitaki, Peter W. Graham, and Surjeet Rajendran; Simone Giombi and Xi Yin; and Frans Pretorius New Horizons in Mathematics Prize awarded to Mohammad Abouzaid, Hugo Duminil-Copin, and Benjamin Elias and Geordie Williamson Second Annual, International Breakthrough Junior Challenge Won by Female Students Antonella Masini, 18 (Peru) and Deanna See, 17 (Singapore) 2016 Special Breakthrough Prize in Fundamental Physics, awarded in May to founders and team members of LIGO, awarded to Kip Thorne, Rainer Weiss and family of Ronald Drever Laureates to be honored at glittering awards gala hosted by Morgan Freeman, with live performance by Alicia Keys and presentations from Daniel Ek (CEO of Spotify), Jeremy Irons, Mark and Scott Kelly, Hiroshi Mikitani (CEO of Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO of Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO of YouTube) and the founders of the Breakthrough Prize SAN FRANCISCO, Dec. 5, 2016 /PRNewswire/ -- The Breakthrough Prize and founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan, tonight announced the recipients of the 2017 Breakthrough Prizes, marking the organization's fifth anniversary recognizing top achievements in Life Sciences, Fundamental Physics and Mathematics. A combined total of $25 million was awarded at the gala ceremony in Silicon Valley, hosted by Morgan Freeman. Each of the Breakthrough Prizes is worth $3 million, the largest individual monetary prize in science. This year, a total of seven of these prizes were awarded to nine individuals, along with a $3 million Special Breakthrough Prize in Fundamental Physics, which was split between three founders and more than a thousand members of the LIGO team. In addition, three $100,000 New Horizons in Physics Prizes were awarded to six early-career physicists, and a further three $100,000 New Horizons in Mathematics Prizes were awarded to four young mathematicians. And this year there were two winners of the Breakthrough Junior Challenge, each receiving up to $400,000 in educational prizes for them, their teacher and their school. Since its inception in 2012, the Breakthrough Prize has awarded close to $200 million to honor paradigm-shifting research in the fields of fundamental physics, life sciences, and mathematics. "There has never been a more important time to support science," said Facebook founder Mark Zuckerberg. "The 2017 Breakthrough Prize laureates represent the leaders in scientific research in physics, math and life sciences. Their breakthroughs will unlock new possibilities and help make the world a better place for everyone." The 2017 Breakthrough Prize in Life Sciences was awarded to Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Tokyo Institute of Technology); Huda Yahya Zoghbi (Baylor College of Medicine). The 2017 Breakthrough Prize in Fundamental Physics was awarded to Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University); and Cumrun Vafa (Harvard University). The three honorees joined the recipients of the previously announced Special Prize in Fundamental Physics, released in May 2016. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) and Rainer Weiss (Massachusetts Institute of Technology), were recognized in May for their detection of gravitational waves, opening new horizons in astronomy and physics. The three winners of the Special Prize will share a $1 million prize, and 1,012 LIGO team members will share $2 million. The 2017 Breakthrough Prize in Mathematics was awarded to Jean Bourgain (Institute for Advanced Study). This year's ceremony will mark the fifth anniversary of the organization, and laureates will take to the stage tonight at an exclusive gala co-hosted by founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, Mark Zuckerberg and Priscilla Chan, and Vanity Fair editor Graydon Carter. Academy Award®-winning actor Morgan Freeman will host the show, which will feature a performance by 15-time Grammy Award® winner Alicia Keys, and celebrity presenters Jeremy Irons, Mark and Scott Kelly, Hiroshi Mikitani (CEO of Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO of Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO of YouTube), as well as the founders of the Breakthrough Prize. The theme of the evening will be "the universal reach of ideas." "Science is universal," said Yuri Milner. "Tonight it brought together some of the world's greatest actors, sportsmen, musicians, academics, entrepreneurs, astronauts and, last but not least, scientists, to celebrate what the human mind can achieve. And it brought in a live audience from across the planet." One of the highlights will be the speeches by the two female students who won the Breakthrough Junior Challenge, Antonella Masini, 18 (Peru) and Deanna See, 17 (Singapore). The Breakthrough Junior Challenge is a global science video competition designed to inspire creative thinking about fundamental concepts in the life sciences, physics, or mathematics. In recognition of their winning submissions, both students received up to $400,000 in educational prizes, including a scholarship worth up to $250,000, $50,000 for an inspiring teacher, and a state-of-the-art science lab valued at $100,000. Entries from 146 countries were received in the 2016 installment of the global competition, which kicked off on September 1, 2016. The Breakthrough Junior Challenge is funded by Mark Zuckerberg and Priscilla Chan, and Yuri and Julia Milner, through the Breakthrough Prize Foundation, based on a grant from Mark Zuckerberg's fund at the Silicon Valley Community Foundation, and a grant from the Milner Global Foundation. "The Breakthrough Junior Challenge encourages students to better understand the worlds of science and mathematics and to have some fun along the way," said Breakthrough Prize co-founder Dr. Priscilla Chan. "Antonella and Deanna both have bright futures in science and I am so excited to honor their work. They are also incredible storytellers, whose ability to capture these complex ideas in accessible and exciting ways is truly inspiring. I cannot wait to see how they will change the world." In addition, six New Horizons prizes – an annual prize of $100,000 each, recognizing the achievements of early-career physicists and mathematicians – were awarded. The New Horizons in Physics Prize was awarded to: The New Horizons in Mathematics Prize was awarded to: The ceremony will be directed and produced, for the fourth time, by Don Mischer alongside executive producers Charlie Haykel and Juliane Hare of Don Mischer Productions. Broadcast live in its entirety on NATIONAL GEOGRAPHIC at 10/9c on Sunday, Dec. 4, an edited one-hour version of the ceremony will also air on FOX on Sunday, Dec. 18, at 7:00-8:00 PM ET/PT and globally on NATIONAL GEOGRAPHIC in 171 countries and 45 languages. The Breakthrough Prize in Life Sciences honors transformative advances towards understanding living systems and extending human life, with one prize dedicated to work that contributes to the understanding of neurological diseases. Each of the five Life Science winners received a $3 million prize. Stephen J. Elledge, Gregor Mendel Professor of Genetics and Medicine in the Department of Genetics at Harvard Medical School and in the Division of Genetics at the Brigham and Women's Hospital and Investigator with the Howard Hughes Medical Institute, for elucidating how eukaryotic cells sense and respond to damage in their DNA and providing insights into the development and treatment of cancer. Harry F. Noller, Director of the Center for Molecular Biology of RNA, Robert L. Sinsheimer Professor of Molecular Biology and Professor Emeritus of MCD Biology at the University of California, Santa Cruz, for discovering the centrality of RNA in forming the active centers of the ribosome, the fundamental machinery of protein synthesis in all cells, thereby connecting modern biology to the origin of life and also explaining how many natural antibiotics disrupt protein synthesis. Roeland Nusse, Professor of Developmental Biology at Stanford University and Investigator at Howard Hughes Medical Institute, for pioneering research on the Wnt pathway, one of the crucial intercellular signaling systems in development, cancer and stem cell biology. Yoshinori Ohsumi, Honorary Professor, Institute of Innovative Research at Tokyo Institute of Technology for elucidating autophagy, the recycling system that cells use to generate nutrients from their own inessential or damaged components. Huda Yahya Zoghbi, Professor in the Departments of Pediatrics, Molecular and Human Genetics, Neurology and Neuroscience at Baylor College of Medicine, Investigator at the Howard Hughes Medical Institute and Director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children's Hospital, for discoveries of the genetic causes and biochemical mechanisms of spinocerebellar ataxia and Rett syndrome, findings that have provided insight into the pathogenesis of neurodegenerative and neurological diseases. The Breakthrough Prize in Fundamental Physics recognizes major insights into the deepest questions of the universe. The three winners, sharing the $3 million prize, are: Joseph Polchinski, Professor in the Department of Physics and Member of the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara; Andrew Strominger, Director of the Center for the Fundamental Laws of Nature at Harvard University; and, Cumrun Vafa, Donner Professor of Science in the Department of Physics at Harvard University, All three received the Prize for transformative advances in quantum field theory, string theory, and quantum gravity. The Breakthrough Prize in Mathematics honors the world's best mathematicians who have contributed to major advances in the field. Jean Bourgain, IBM von Neumann Professor in the School of Mathematics at the Institute for Advanced Study, Princeton, New Jersey, for multiple transformative contributions to analysis, combinatorics, partial differential equations, high-dimensional geometry and number theory. The New Horizons in Physics Prize is awarded to promising early-career researchers who have already produced important work in fundamental physics. The New Horizons in Mathematics Prize is awarded to promising early-career researchers who have already produced important work in mathematics. The second annual Breakthrough Junior Challenge recognizes two winners this year - Antonella Masini, 18, from Peru, and Deanna See, 17, from Singapore. Antonella and Deanna will each receive up to $400,000 in educational prizes. Antonella's video, submitted in the physics category, focused on quantum entanglement. Deanna's life sciences video, titled "Superbugs! And Our Race against Resistance," tackled antibiotic resistance. Images and select video from the 2017 Breakthrough Prize Gala -red carpet and ceremony- can be downloaded for media use at: For the fifth year, the Breakthrough Prizes will recognize the world's top scientists. Each prize is $3 million and awarded in the fields of Life Sciences (up to five per year), Fundamental Physics (up to one per year) and Mathematics (up to one per year). In addition, up to three New Horizons in Physics and up to three New Horizons in Mathematics Prizes are given out to junior researchers each year. Laureates attend a televised awards ceremony designed to celebrate their achievements and inspire the next generation of scientists. As part of the ceremony schedule, they also engage in a program of lectures and discussions. The Breakthrough Prizes were founded by Sergey Brin and Anne Wojcicki, Mark Zuckerberg and Priscilla Chan, and Yuri and Julia Milner. Selection Committees composed of previous Breakthrough Prize laureates choose the winners. Information on the Breakthrough Prizes is available at www.breakthroughprize.org.


News Article | October 26, 2016
Site: www.eurekalert.org

People with Icelandic heritage are more likely to carry a novel rare mutation in the TM2D3 gene, which leads to greater risk for Alzheimer's disease, based on a new study published October 14th, 2016 in PLOS Genetics by Johanna Jakobsdottir of the Icelandic Heart Association, Sven van der Lee of Erasmus University in Rotterdam, and colleagues. Alzheimer's disease is the most common form of dementia, affecting about 30% of adults above the age of 85. While scientists have already identified many common genetic variants that contribute to the disease, rare mutations with significant effects in the population have been more difficult to discover, except in rather isolated families. To find such rare variations, a collaboration of Alzheimer's researchers throughout the U.S. and Europe performed an analysis covering more than 11,000 genes in 1,393 late-onset Alzheimer's disease patients. They identified a variant in the TM2D3 gene that is associated with both a higher risk and earlier age of onset of Alzheimer's disease. Interestingly, the TM2D3 genetic variant is about 10 times more common in Icelanders compared to the European population in general. Nevertheless, the variant remains quite rare and is present in fewer than 1% of the Icelandic population, and the prevalence of Alzheimer's disease in Iceland is comparable to that seen elsewhere in the world. The researchers also performed experiments in a fruit fly model, in which human TM2D3 was substituted for an equivalent fly gene, demonstrating that the discovered variant interferes with the Notch signaling pathway. Other Notch signaling factors have previously been shown to participate in the generation of amyloid plaque brain pathology in Alzheimer's disease. Jakobsdottir, van der Lee and colleagues have identified a rare genetic variant associated with Alzheimer's risk, and propose a possible function to explain its role in the disease. The TM2D3 gene has not previously been linked to Alzheimer's, and thus may have importance for understanding the mechanisms that contribute to the late-onset form of the disease. Johanna adds "We have found a rare variant in the TM2D3 gene that correlates with risk of late-onset Alzheimer's disease and showed that it likely interferes with the Notch signaling pathway, which has relevance for Alzheimer's disease as other Notch signaling factors play a role in amyloid plaque pathology. However, we have not proven causality and further study is needed, including additional experiments in the fly, DNA sequencing to identify additional variants, and RNA sequencing to study effects on gene expression." In your coverage please use this URL to provide access to the freely available article in PLOS Genetics: http://dx. Citation: Jakobsdottir J, van der Lee SJ, Bis JC, Chouraki V, Li-Kroeger D, Yamamoto S, et al. (2016) Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease. PLoS Genet 12(10): e1006327. doi:10.1371/journal.pgen.1006327 Funding: Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute (NHLBI, http://www. ) grant HL105756. Funding support for the CHARGE Consortium Exome Chip analyses is provided in part by the NHLBI grant HL120393. Support for centralized calling of the exome chip was provided by Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium through the National Institutes of Health (NIH, https:/ ) American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). The CHARGE consortium is a founding component of the Alzheimer's Disease Sequencing Project, and receives sequencing and analysis support through the grants from NIH: U01-AG049506, U01-AG049505, and U54-HG003273. AGES study is supported by the National Institute on Aging (NIA, https:/ ) contracts N01-AG-12100 and HHSN271201200022C with contributions from the National Eye Institute (NEI, https:/ ), National Institute on Deafness and Other Communication Disorders (NIDCD, https:/ ), NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). JMS was supported by grants from the NIH/NIA (R01-AG033193, R01-AG050631, C06-RR029965), the Alzheimer's Association, the American Federation for Aging Research, Huffington Foundation, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, and a Career Award for Medical Scientists from the Burroughs Wellcome Fund. The work was additionally supported by U54HD083092 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. SY was supported by the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and the Alzheimer's Association. HJB is a Howard Hughes Medical Institute Investigator and also received support from the Robert and Renee Belfer Family Foundation, the Huffington Foundation, and Target ALS. JS is supported by NIH GMR2556929. Detailed funding information for all studies that contributed to this work are provided in S1 Text Funding section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.


News Article | October 7, 2016
Site: www.rdmag.com

Taking a pill that prevents the accumulation of toxic molecules in the brain might someday help prevent or delay Alzheimer's disease, according to scientists at Baylor College of Medicine, Texas Children's Hospital and Johns Hopkins University School of Medicine. The study, published today in Cell Press journal Neuron, took a three-pronged approach to help subdue early events that occur in the brain long before symptoms of Alzheimer's disease are evident. The scientists were able to prevent those early events and the subsequent development of brain pathology in experimental animal models in the lab. "Common diseases like Parkinson's, Alzheimer's and dementia are caused in part by abnormal accumulation of certain proteins in the brain," said senior author Dr. Huda Zoghbi, professor of molecular and human genetics and of pediatrics - neurology and developmental neuroscience at Baylor and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. "Some proteins become toxic when they accumulate; they make the brain vulnerable to degeneration. Tau is one of those proteins involved in Alzheimer's disease and dementia." "Scientists in the field have been focusing mostly on the final stages of Alzheimer's disease," said first author Cristian Lasagna-Reeves, postdoctoral fellow in the Zoghbi lab. "Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later." The scientists reasoned that if they could find ways to prevent or reduce tau accumulation in the brain, they would uncover new possibilities for developing drug treatments for these diseases. Cells control the amount of their proteins with other proteins called enzymes. To find which enzymes affect tau accumulation, the scientists systematically inhibited enzymes called kinases. "We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau," said Zoghbi, who is also an investigator at the Howard Hughes Medical Institute. The scientists screened the enzymes in two different systems, cultured human cells and the laboratory fruit fly. Screening in the fruit fly allowed the scientists to assess the effects of inhibiting the enzymes in a functional nervous system in a living organism. "Screening hundreds of kinases in the fruit fly animal model was critical because we could assess degeneration caused by tau in the fly's nervous system and measure neuronal dysfunction. Screening such a large number cannot be done with other animal models like the mouse, and cultured cells cannot model complex nervous system functions," said co-senior author Juan Botas, Ph.D., professor of molecular and human genetics and of molecular and cellular biology at Baylor. "We found one enzyme, Nuak1, whose inhibition consistently resulted in lower levels of tau in both human cells and fruit flies," said Zoghbi. "Then we took this result to a mouse model of Alzheimer's disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improved the behavior of the mice and prevented brain degeneration." "Confirming in three independent systems – human cells, the fruit fly and the mouse – that Nuak1 inhibition results in reduced levels of tau and prevents brain abnormalities induced by tau accumulation, has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer's," said Zoghbi. "The next step is to develop drugs that will inhibit Nuak1 in hope that one day would be able to lower tau levels with low toxicity in individuals at risk for dementia due to tau accumulation." Scientific studies like this one that uncover basic biological mechanisms of disease make it possible to develop new strategies to prevent or treat diseases such as Alzheimer's, Parkinson's or dementia. In the future it might be possible to treat people at risk for Alzheimer's disease by keeping tau low. Think of how taking drugs that lower cholesterol has helped control the accumulation of cholesterol in blood vessels that leads to atherosclerosis and heart disease. "When people started taking drugs that lower cholesterol, they lived longer and healthier lives rather than dying earlier of heart disease," said Zoghbi. "Nobody has thought about Alzheimer's disease in that light. Tau in Alzheimer's can be compared to cholesterol in heart disease. Tau is a protein that when it accumulates as the person ages, increases the vulnerability of the brain to developing Alzheimer's. So maybe if we can find drugs that can keep tau at levels that are not toxic for the brain, then we would be able to prevent or delay the development of Alzheimer's and other diseases caused in part by toxic tau accumulation." "Just like people now take their cholesterol-lowering medications, people in the future could be taking medications to keep tau levels low and prevent the development of Alzheimer's disease," said Lasagna-Reeves.


News Article | October 25, 2016
Site: www.gizmag.com

Could we fight Alzheimer's with medication the way we fight high cholesterol? New research offers hope(Credit: Siphotography/ Depositphotos ) Nuak1. It sounds like it could be the name of an android or a distant moon in an upcoming sci-fi film. It is, in fact, an enzyme that recent research shows plays a key role in creating a protein in the brain that contributes to Alzheimer's disease. Manipulating Nuak1 to our advantage could eventually make treating the condition akin to fighting cholesterol with statins, say scientists. In a study published in the journal Neuron, researchers describe how they turned their attention to a protein called tau that becomes toxic to the brain when it builds up in excessive quantities, and has been linked to Alzheimer's and dementia. Limiting tau, they reasoned, might just limit the neurodegeneration that occurs with the diseases. And one way to limit tau is to find the enzyme that helps cells produce it. They hunted for the right compound by inhibiting 600 different enzymes called kinases in human cells and in fruit flies. They found that when they inhibited Nuak1, the levels of tau dropped. "Screening hundreds of kinases in the fruit fly animal model was critical because we could assess degeneration caused by tau in the fly's nervous system and measure neuronal dysfunction," said co-senior author Dr. Juan Botas, professor of molecular and human genetics and of molecular and cellular biology at Baylor College of Medicine. "Screening such a large number cannot be done with other animal models like the mouse, and cultured cells cannot model complex nervous system functions." Speaking of mice however, the research team's next step was to see if their discovery would hold in tests using the rodents. It did. "Inhibiting Nuak1 improved the behavior of the mice and prevented brain degeneration," said senior author Huda Zoghbi, a professor at Baylor and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. Because the researchers had positive results across three systems – human cells, fruit fly and mouse – they feel hopeful that drug treatment based on Nuak1 could help battle Alzheimer's and other types of dementia. In fact, says Zoghbi, the treatment could one day be as simple as taking a statin to fight high cholesterol is today. "When people started taking drugs that lower cholesterol, they lived longer and healthier lives rather than dying earlier of heart disease," she said. "Nobody has thought about Alzheimer's disease in that light. "Tau in Alzheimer's can be compared to cholesterol in heart disease. Tau is a protein that when it accumulates as the person ages, increases the vulnerability of the brain to developing Alzheimer's. So maybe if we can find drugs that can keep tau at levels that are not toxic for the brain, then we would be able to prevent or delay the development of Alzheimer's and other diseases caused in part by toxic tau accumulation."


News Article | October 24, 2016
Site: www.biosciencetechnology.com

Taking a pill that prevents the accumulation of toxic molecules in the brain might someday help prevent or delay Alzheimer's disease, according to scientists at Baylor College of Medicine, Texas Children's Hospital and Johns Hopkins University School of Medicine. The study, published today in Cell Press journal Neuron, took a three-pronged approach to help subdue early events that occur in the brain long before symptoms of Alzheimer's disease are evident. The scientists were able to prevent those early events and the subsequent development of brain pathology in experimental animal models in the lab. "Common diseases like Parkinson's, Alzheimer's and dementia are caused in part by abnormal accumulation of certain proteins in the brain," said senior author Dr. Huda Zoghbi, professor of molecular and human genetics and of pediatrics - neurology and developmental neuroscience at Baylor and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. "Some proteins become toxic when they accumulate; they make the brain vulnerable to degeneration. Tau is one of those proteins involved in Alzheimer's disease and dementia." "Scientists in the field have been focusing mostly on the final stages of Alzheimer's disease," said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow in the Zoghbi lab. "Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later." The scientists reasoned that if they could find ways to prevent or reduce tau accumulation in the brain, they would uncover new possibilities for developing drug treatments for these diseases. Cells control the amount of their proteins with other proteins called enzymes. To find which enzymes affect tau accumulation, the scientists systematically inhibited enzymes called kinases. "We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau," said Zoghbi, who is also an investigator at the Howard Hughes Medical Institute. The scientists screened the enzymes in two different systems, cultured human cells and the laboratory fruit fly. Screening in the fruit fly allowed the scientists to assess the effects of inhibiting the enzymes in a functional nervous system in a living organism. "Screening hundreds of kinases in the fruit fly animal model was critical because we could assess degeneration caused by tau in the fly's nervous system and measure neuronal dysfunction. Screening such a large number cannot be done with other animal models like the mouse, and cultured cells cannot model complex nervous system functions," said co-senior author Dr. Juan Botas, professor of molecular and human genetics and of molecular and cellular biology at Baylor. Brain section from mouse carrying the dementia-causing P301S mutation in human tau shows accumulation of tau neurofibrillary tangles (in dark brown, left). When Nuak1 levels are decreased by 50% (P301S/Nuak1+/-; right), fewer tau tangles accumulate. "We found one enzyme, Nuak1, whose inhibition consistently resulted in lower levels of tau in both human cells and fruit flies," said Zoghbi. "Then we took this result to a mouse model of Alzheimer's disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improved the behavior of the mice and prevented brain degeneration." "Confirming in three independent systems - human cells, the fruit fly and the mouse - that Nuak1 inhibition results in reduced levels of tau and prevents brain abnormalities induced by tau accumulation, has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer's," said Zoghbi. "The next step is to develop drugs that will inhibit Nuak1 in hope that one day would be able to lower tau levels with low toxicity in individuals at risk for dementia due to tau accumulation." Scientific studies like this one that uncover basic biological mechanisms of disease make it possible to develop new strategies to prevent or treat diseases such as Alzheimer's, Parkinson's or dementia. In the future it might be possible to treat people at risk for Alzheimer's disease by keeping tau low. Think of how taking drugs that lower cholesterol has helped control the accumulation of cholesterol in blood vessels that leads to atherosclerosis and heart disease. "When people started taking drugs that lower cholesterol, they lived longer and healthier lives rather than dying earlier of heart disease," said Zoghbi. "Nobody has thought about Alzheimer's disease in that light. Tau in Alzheimer's can be compared to cholesterol in heart disease. Tau is a protein that when it accumulates as the person ages, increases the vulnerability of the brain to developing Alzheimer's. So maybe if we can find drugs that can keep tau at levels that are not toxic for the brain, then we would be able to prevent or delay the development of Alzheimer's and other diseases caused in part by toxic tau accumulation." "Just like people now take their cholesterol-lowering medications, people in the future could be taking medications to keep tau levels low and prevent the development of Alzheimer's disease," said Lasagna-Reeves.

Loading Jan and Dan Duncan Neurological Research Institute collaborators
Loading Jan and Dan Duncan Neurological Research Institute collaborators