The 24th Colloque Médecine et Recherche in the Neurosciences Series of the Fondation Ipsen: “Genome editing in neurosciences”
A new method for making precise changes in selected genes is taking the world of biomedical research by storm. Known by the rather inelegant name of CRISPR-Cas9, it is a rapid, efficient, versatile and relatively cheap tool for dissecting the molecular pathways that are the basis of life, as well as for investigating and potentially rectifying faults in these pathways that result in disease. During this Colloque Médecine et Recherche in Neurosciences organized by the Fondation Ipsen, an international panel of speakers reviewed how this and other genome editing techniques are advancing understanding of the development and functioning of the nervous system. A special focus has been on the combination of genome editing with recent developments in stem cell technology, which is proving particularly powerful for uncovering the mechanisms of, and developing treatments for, a range of neurological disorders. The scientific committee included Rudolf Jaenisch (MIT, Cambridge, USA), Feng Zhang (MIT, Cambridge, USA), Fred Gage (Salk Institute for Biological Studies, La Jolla, USA) and Yves Christen (Fondation Ipsen, Paris, France).
Genes are the blueprints for making proteins, the complex molecules that provide both the structural and functional organisation of all forms of life. A mutation in a gene may result in the protein being misshapen, shortened or absent, causing a hiccup in a biological process that may cause disease or death. The roles of healthy or mutated proteins have been investigated for many years by studying what happens in the organism when single genes are silenced or their activity enhanced. Although used extensively and productively, these methods are cumbersome, expensive and not very reliable. In the past five years, a new generation of techniques have been developed that use enzymes known as endonucleases to make precisely positioned cuts in DNA. Harnessing the natural mechanisms for repairing breaks in DNA found in every cell, these ‘molecular scissors’ can be used to remove, alter or replace small sequences of DNA; the changes resulting from the operation can be examined either in single cells in culture or in whole organisms. The most effective of these editing tools, known as CRISPR-Cas9, is derived from a natural immune defence mechanism found in bacteria and in the past two years has been adapted for use in a variety of organisms and with wide applications in research, medicine and crop breeding (Emmanuelle Charpentier, Max Planck Institute, Berlin, Germany). It provides a rapid way to examine the sea of variations in gene sequences between individuals and to identify those that cause problems, which will be of fundamental importance in personalised medicine (Zhang).
The rest of the presentations focused on the applications of CRISPR-Cas9 and other editing methods in nervous system development, function and disease. In development, gene editing is enabling the study of the dynamics of gene regulation in real-time in single cells as they become differentiated into specific functional types (Jaenisch). Rapid genomic screening of neural stem cells is giving an insight into vulnerability to mental illness: genes associated with establishing neural connections and synaptic function contain breaking regions in the DNA that are susceptible to stress (Frederick Alt, Children’s Hospital, Harvard Medical School, Boston, USA). The study of fish brains is contributing to understanding how nervous systems regenerate. Because they grow throughout life, these brains contain populations of active stem cells, which can be manipulated with tools such as CRISPR-Cas9 to provide information about the conditions controlling cell division in the generation of new neurons (Jean-Stéphane Joly, CNRS/INRA, University Paris-Saclay, Gif-sur-Yvette, France).
Much has already be learned about synaptic function with the now-old-fashioned methods of gene silencing but use of CRIPSR-Cas 9 is allowing a far more refined dissection of molecular mechanisms. Molecules previously thought to be active only when synaptic function changes during memory formation are now being found also to have an essential role in the on-going maintenance of the synapses of some neurons (Salvatore Incontro, University of California, San Francisco, USA). The CRISPR-Cas 9 method is also being applied on the whole-cell level in zebra fish to study how neural circuits become hooked-up during development. Specific types of neurons can be identified by genetic targeting of protein markers, which can be visualised in real time as the fish larva are almost transparent (Filippo del Bene, Institut Curie, Paris, France).
Genome editing adds an extra layer of sophistication to another already powerful biomedical research tool, induced pluripotent stem cells (iPSCs have been the topic of two previous Fondation Ipsen meetings: Programmed cells : from basic neuroscience to therapy, Paris, April 2012 and Stem cells in neuroendocrinology, Paris, December 2015. Skin cells taken from a patient can be made to revert to undifferentiated stem cells in vitro and now CRISPR-Cas9 is being used to correct disease-related genetic defects before the stem cells undergo differentiation into particular cell types, with the ultimate goal of replacing the patient’s damaged cells. Such stem cells are being used for investigating the effects of specific, disease-related mutations by creating isogenic cell lines: colonies of cells with identical genomes except that one has the normal copy of the gene, the other the mutated one. Application include determining the effects of genes that increase the risk of developing Parkinson’s disease on neuron function (Jaenisch); examining the deficits in neuronal function related to mutations linked to autism (Neville Sanjana, Broad Institute, Cambridge, USA); investigating why myelin production is disrupted by the mutation that causes the fatal congenital Pelizaeus-Merzbacher disease (Marius Wernig, Institute for Stem Cell Biology and Regenerative Medicine, Stanford, USA); and determining why only certain types of neuron are susceptible to the mutant protein that causes Huntington’s disease (Lisa Ellerby, Buck Institute for Research on Aging, Novato, USA). Genetic screens of single cells are also being used to analyse how this mutant protein affects cell function (Myriam Heiman, MIT, Cambridge, USA).
A proof-of-principle experiment to bypass the gene defect causing Duchenne muscular dystrophy is having some success in mice, using a specially designed CRISPR-Cas9 to modify the mutant gene, a taste of future therapies for presently intractable genetic diseases (Amy Wagers, Joslin Diabetes Center, Harvard Medical School, Boston, USA). Bringing animal models closer to humans, the common marmoset, a primate that is both easy to breed and has close similarities to humans than the more commonly used macaque monkeys, is now being genetically modified to mimic symptoms of various human neurodevelopmental and neurodegenerative diseases (Hideyuki Okano, Keio University, Tokyo, Japan).
The meeting provided a snapshot of this fast growing field, a taste of the wide range of creative ways in which these genome-editing tools are being applied, and a look to their future use in the development of personalised medicine.
About the Fondation Ipsen
Established in 1983 under the aegis of the Fondation de France, the mission of the Fondation Ipsen is to contribute to the development and dissemination of scientific knowledge. The long-standing action of the Fondation Ipsen aims at fostering the interaction between researchers and clinical practitioners, which is indispensable due to the extreme specialization of these professions. The ambition of the Fondation Ipsen is to initiate a reflection about the major scientific issues of the forthcoming years. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Médecine et Recherche, dedicated to three main themes: neurosciences, endocrinology and cancer science. Moreover the Fondation Ipsen has started since 2007 several meetings in partnership with the Salk Institute, the Karolinska Institutet, the Massachusetts General Hospital, the Days of Molecular Medicine Global Foundation as well as with the science journals Nature, Cell and Science. The Fondation Ipsen produced several hundred publications; more than 250 scientists and biomedical researchers have been awarded prizes and research grants.
Isabelle de Segonzac,Tel. : +33 (0)1 53 70 74 70
E-mail : email@example.com
Om Business Wire
(c) 2018 Business Wire, Inc., All rights reserved.
Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.
Følg saker fra Business Wire
Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.
Siste saker fra Business Wire
WELL Building Standard Gaining Momentum in Europe18.5.2018 14:47 | Pressemelding
As Greenbuild Europe came to a close in Berlin, the International WELL Building Institute™ (IWBI™) used the occasion to highlight how the WELL Building Standard™ (WELL™) has elevated health and well-being to the forefront of sustainability conversations across Europe. WELL continues to advance the healthy building movement as the premier standard for buildings, interior spaces and communities seeking to implement, validate and measure features that promote human health and wellness. The resonance of the program has spurred innovations across the building, design and construction industries, providing projects with customizable approaches to address geographical and cultural health concerns. To date, WELL has enrolled more than 830 projects encompassing over 155 million square feet of real estate in 32 countries worldwide. In Europe nearly 190 projects across 13 countries are engaged with WELL, representing 25% of global WELL project square footage. The strong growth of WELL over the pa
Utimaco Announces Intent to Acquire Atalla from Micro Focus18.5.2018 09:03 | Pressemelding
Utimaco, the global #2 in Hardware Security Modules (HSMs), today announced the intent to acquire the Atalla HSM and ESKM business lines from Micro Focus, which were previously owned by Hewlett Packard Enterprise (HPE) prior to the September 2017 merger of its Software business with Micro Focus. Germany-based Utimaco, active in the HSM market for over 35 years, is a global manufacturer of general purpose HSMs. Utimaco has built its market leading position focusing on indirect sales through OEM or channel business partners and selling its SecurityServer product line into industries as diverse as automotive, government, media & entertainment, smart metering, semiconductors, telecommunications and the banking and financial services sectors. Utimaco is traditionally strong in its German home market based on its longstanding German banking association certification (DK) and has recently achieved PCI accreditation for the SecurityServer product line. With the acquisition of Atalla, one of th
Janssen to Present New Data in Urothelial, Haematologic and Prostate Cancers at ASCO 2018, including Best of ASCO Selections18.5.2018 07:00 | Pressemelding
The Janssen Pharmaceutical Companies of Johnson & Johnson, today announced 21 company-sponsored abstracts will be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL on June 1-5. New data analyses in support of a portfolio of products, including the investigational treatments erdafitinib and apalutamide, as well as approved treatments Imbruvica® (ibrutinib), Darzalex® (daratumumab), and Zytiga® (abiraterone acetate) will be highlighted across urothelial, haematologic and prostate cancers. Notably, Phase 2 trial results for the investigational compound erdafitinib, which received U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation, will be presented during an oral presentation on Sunday, June 3 (Abstract #4503).1,2 For haematologic cancers, Phase 3 data from the iNNOVATE study will provide the first look at ibrutinib plus rituximab versus placebo plus rituximab in patients with newly diagnosed and relapsed/refractory Wald
Karisma Hotels & Resorts to Open Allure Palazzi Kotor Bay Hotel by Karisma in June 201818.5.2018 06:00 | Pressemelding
Karisma Hotels & Resorts, an award-winning luxury hotel collection which owns and manages properties in Latin America, the Caribbean and Europe, is pleased to announce the opening of Allure Palazzi Kotor Bay Hotel by Karisma in June 2018. Built from the ground up in Montenegro’s idyllic Dobrota, the exclusive five-star beachfront property seamlessly blends stunning architecture and design with its mountainous landscape, offering spellbinding views of Kotor Bay. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180517006456/en/ Rendering of Allure Palazzi Kotor Bay (Photo: Business Wire) Sitting on Kotor Bay’s only private beach, the resort features 89 premium guestrooms, 10 villas with private beachfront access, and three breathtaking penthouse suites, each with a balcony or terrace. Allure Palazzi Kotor Bay’s accommodations encompass sumptuous bedding, divine amenities, and carefully selected color palettes bringing the sunny
Siemens Financial Services Selects GTC’s @GlobalTrade Platform for Management of Export Documentary Credits18.5.2018 04:00 | Pressemelding
GlobalTrade Corporation (GTC) has announced today that Siemens Financial Services (SFS) has selected its @GlobalTrade Multi-bank Trade Finance Platform for management of its export documentary credits. The platform will be initially rolled out in Germany and thereafter expanded to Siemens entities globally. The system will electronically aggregate all incoming documentary credits in a global database, facilitate review and approval, assist in preparation of compliant documents and enable faster presentation of documents electronically to advising and issuing banks. Gerhard Heubeck, Head of Trade Finance Advisory at Siemens Financial Services, reasons the need for the new system implementation as follows: "After many years of using one of the first standard IT systems available for export documentary credits, the time has come to find a successor tool capable to meet the new requirements such as multi-client capability, processing of new SWIFT message formats, global accessibility, and
PayPal Significantly Expands Global Omnichannel Platform With Acquisition of iZettle17.5.2018 22:35 | Pressemelding
PayPal Holdings, Inc. (NASDAQ: PYPL) announced today that it has agreed to acquire iZettle, the leading small business commerce platform in Europe and Latin America, for $2.2 billion USD. The acquisition of iZettle significantly expands PayPal’s in-store presence, strengthening PayPal’s platform to help millions of small businesses around the world grow and thrive in an omnichannel retail environment. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180517006443/en/ Left to right: Jacob de Geer, CEO and Co-Founder of iZettle, Dan Schulman, President and CEO of PayPal, and Bill Ready, EVP, Chief Operating Officer of PayPal. (Photo: Business Wire) “Small businesses are the engine of the global economy and we are continuing to expand our platform to help them compete and win online, in-store and via mobile,” said PayPal President and CEO Dan Schulman. “iZettle and PayPal are a strategic fit, with a shared mission, values and cult