Aimera.Gutierrezdıaz.2017.Pdf (6.190Mb)

Total Page:16

File Type:pdf, Size:1020Kb

Aimera.Gutierrezdıaz.2017.Pdf (6.190Mb) Detecci´onautomatizada de peque~nos fragmentos derivados de RNAs no-codificantes expresados diferencialmente frente a la infecci´ondel virus Dengue Aimer Alonso Guti´errezD´ıaz Universidad Nacional de Colombia Facultad de Ingenier´ıa,Departamento de Ingenier´ıade Sistemas e Industrial Maestr´ıaen Bioinform´atica Bogot´aD.C., Colombia A~no2017 Detecci´onautomatizada de peque~nos fragmentos derivados de RNAs no-codificantes expresados diferencialmente frente a la infecci´ondel virus Dengue Aimer Alonso Guti´errezD´ıaz Tesis presentada como requisito parcial para optar al t´ıtulode: Magister en Bioinform´atica Directora: Ph.D. Clara Isabel Berm´udezSantana Departamento de Biolog´ıa,Universidad Nacional de Colombia. Co-Director: Ph.D. Steve Hoffmann Friedrich Schiller University Jena, Alemania L´ıneade Investigaci´on: Transcript´omicade RNA no codificantes Grupo de Investigaci´on: Grupo RNomica te´oricay computacional Universidad Nacional de Colombia Facultad de Ingenier´ıa,Departamento de Ingenier´ıade Sistemas e Industrial Bogot´aD.C., Colombia A~no2017 Lema "... Gene differences do not cause evolutionary changes in populations, they (just) register those changes." S. J. Gould (2002). "... La meta m´asdif´ıcil de alcanzar no es la riqueza ni el poder. No se trata de algo material, no es ning´unt´ıtulo de la universidad, no est´a en buscar, est´aen el ser". "Libre". Paradoxus luporum, 2014 Agradecimientos A la vida, que me ha permitido indagar en uno de sus tantos secretos. A la direcci´onde la profesora Clara Isabel Berm´udezSantana y el profesor Steve Hoffman, quienes me acompa~naron,apoyaron y orientaron permanentemente en un viaje a trav´esde un mar de datos. Al profesor Juan Carlos Gallego G´omezy Diego Alejandro Alvarez del grupo de Medici- na Molecular y de Translaci´on,por sus valioso aporte te´orico-conceptual,experimental y ´etico. A Carlos Andr´esRodriguez Salazar y al profesor Jhon Carlos Casta~noOsorio del Grupo de Inmunolog´ıaMolecular de la Facultad Ciencias de la Salud de la Universidad del Quind´ıo,quienes contribuyeron en el diagn´osticoy colecci´onde las muestras de sangre empleadas en el presente estudio. Al servicio de intercambio acad´emicoAlem´anDAAD, por la donaci´onde la infraes- tructura computacional donde se ejecut´oel presente proyecto A Jens Steuck por su noble y ejemplar gesti´ondel servidor A Luis Alfonso Mej´ıaMu~noz,Gloria Ines Agudelo Roa, Luis Alfonso Mej´ıaAgudelo y Laura Alejandra Mej´ıaAgudelo quienes me apoyaron y acogieron como un miembro m´asde su familia. A mis compa~nerosy amigos del lab: Andres Puerta Gonzalez, Jenny Ortega Rojas, Oscar Javier Escobar, Cristian Arley Velandia, Alejandro Cer´on,Ernesto Parra Rinc´on, Tatiana Garcia y Luz Stefany Botero, por compartir un espacio de formaci´onpersonal y profesional. A la nueva generaci´onde RNOmicos:´ Gabriel Hernandez, Valeria Cadena, Valentina Cobo, Astrid Olave, Edna Romero y Laura Nova. A mis amigos: Cristian Cortes, Ricardo Barrera, Axl Stivel, Mauro Adr´ıany Daniel Arias, por tantos buenos momentos. Resumen En los ´ultimosa~nos,el uso cada vez mayor de las tecnolog´ıasde secuenciaci´onde nueva gene- raci´onpara el estudio del transcriptoma ha llevado al descubrimiento de un nuevo fen´omeno biol´ogicollamado fragmentaci´onpostranscripcional funcional de ncRNAs. Varios estudios han identificado un amplio n´umerode peque~nosfragmentos derivados del procesamiento al- ternativo de ncRNAs (sfd-RNA) que var´ıanentre 16 y 40nt, cuyas fuentes son principalmente tRNAs y snoRNAs. El inter´esen los sfd-RNA se debe a su parecido estructural y funcional con los micro RNAs (miRNAs). Por ejemplo, ambos tipos de mol´eculaspueden cargarse en prote´ınasArgonauta, quienes han sido vinculadas al fen´omenode interferencia mediada por RNA. A la fecha existen diferentes pipelines y herramientas computacionales dirigidas a anotar y evaluar expresi´ondiferencial (DE) de miRNAs; no obstante, su extensi´onpara el estudio de sfd-RNAs no es del todo adecuada, debido a que la fuente de los sfd-RNAs es a su vez una secuencia de ncRNA con una funci´onalternativa, lo que implica una biog´enesisdiferente y por ende requiere estrategias computacionales propias. En particular, para el an´alisisde expresi´ondiferencial de sfd-RNAs, a diferencia de los miRNAs, existen problemas asocia- dos a la detecci´on, anotaci´ony cuantificaci´onde las lecturas asociadas al ncRNA, que en t´erminosestad´ısticos,impactan el n´umerode variables y el tama~node muestra; por ende, se requiere una estrategia de anotaci´onpropia para sfd-RNA capaz de afrontar dos compli- caciones de orden bioinform´atico.La primera de ellas reside en que las mol´eculasfuente de sfd-RNAs presentan un mayor n´umerode copias id´enticas en el genoma con respecto a los miRNAs, a pesar de ello, del conjunto de loci repetitivos no todos necesariamente se trans- criben o no todos los transcritos generados se procesan de manera alternativa para generar fragmentos funcionales. La segunda dificultad yace en discriminar las lecturas derivadas del secuenciamiento de RNAs peque~nosque evidencian la expresi´onde un fragmento funcional a la expresi´ondel ncRNA fuente; debido a que el conjunto de lecturas de un sfd-RNA est´a completamente auto-contenido en el conjunto de secuencias asignado al ncRNA fuente. Las metodolog´ıasrecientes destinadas al estudio de los sfd-RNA se centran exclusivamente en un tipo de fuente de ncRNA (principalmente tRNA) y adolecen de una baja reprodu- cibilidad en sus predicciones, dado a la omis´onde los sezgos de la alineaci´ono por el uso de m´etodos de normalizaci´ondise~nadospara genes codificantes, los cuales son m´aslargos y menos repetitivos. Con el fin de abordar las dificultades previamente descritas para la detecci´ony discriminaci´onde los patrones de expresi´onasociados con sfd-RNAs, y teniendo en cuenta que las herramientas actuales se ocupan de uno de los dos problemas o se centran exclusivamente en una especie de ncRNA, en el presente trabajo se ha dise~nado una nueva estrategia para abordar los dos problemas simult´aneamente. En primer lugar, para evaluar viii diferentes tipos de ncRNAs, se realiz´ola integraci´onde las diferentes familias a trav´esdel solapamiento entre coordenadas de ncRNAs provenientes de bases de datos como UCSC, miRBase, snoRNAbase y RNAcentral, generando un listado de coordenadas de ncRNAs no- redundantes totales, en el que se resaltan solapamientos intra e inter familias. En segundo lugar, adaptando la aproximaci´ondise~nadaen el programa BlockBuster, se utilizaron las coordenadas gen´omicasunificadas como referencia para detectar fragmentos de sfd-RNAs. Para ello, se clasificaron y organizaron las lecturas alineadas a los loci unificados teniendo en cuenta la media o coordenada central de cada lectura. Posterior a su ordenamiento por tama~nose emplearon los valores de media y desviaci´onde la primera lectura para generar una distribuci´onnormal, que es alimentada con la subsecuentes lecturas, bajo la condici´onde que su valor central pertenezca al rango de simetr´ıade la distribuci´onnormal aproximada. Los subgrupos de lecturas generadas fueron definidos como bloques de expresi´onde sfdRNAs sobre los que se evalu´oexpresi´ondiferencial. El estudio de expresi´ondiferencial de sfdRNAs y miRNAs se realiz´obasado en diecis´eisestrategias computacionales que combinan cuatro algoritmos de alineamiento y cuatro m´etodos de normalizaci´oncon el prop´ositode evaluar la reproducibilidad de una predicci´onindependientemente de los m´etodos de alineaci´ony de normalizaci´onempleados. La pipeline desarrollada fue probada con bibliotecas de small-RNAseq derivadas de l´ıneas celulares humanas infectadas por Dengue y muestras de sangre de pacientes humanos con fiebre del dengue y otros estadios febriles con el fin de dar luces a dos problemas biol´ogicosre- lacionados, los determinantes causales del dengue severo y el diagn´osticode las enfermedades febriles agudas inespec´ıficas,respectivamente. Finalmente, el enfoque desarrollado permiti´o abordar tanto los conflictos de anotaci´onde los ncRNAs como tambi´enel correcto uso es- tad´ısticode las lecturas con m´ultiplesalineamientos. Como resultado se encontr´oque ciertos loci detectados como sfd-RNAs hab´ıansido previamente reportados en otras categor´ıascomo piRNAs, adem´as177 fragmentos derivados de tRNAs y 69 snoRNAs est´anambiguamente reportados como miRNAs, piRNAs o siRNAs. Adicionalmente, en el presente trabajo se de- tect´oexpresi´ondiferencial simult´aneamente en miRNAs y sfd-RNA, algunos de estos ´ultimos descritos previamente en la infecci´onviral en humanos por el virus de la hepatitis C. Final- mente, se hall´oexpresi´ondiferencial en miRNAs y sfd-RNAs, los cuales est´anasociados con algunos genes blanco de regulaci´onespec´ıficopara s´ındromesfebriles que pueden ser ´utiles como biomarcadores de s´ındromesfebriles agudos. Palabras clave: Expresi´ondiferencial, Peque~nosncRNAs, anotaci´onde ncRNAs, Bio- marcadores s´ındromefebril, Dengue, Fragmentaci´onpostranscripcional funciona. RESUMEN ix Abstract In recent years, the increasing use of new generation sequencing technologies for trans- criptome study has led to discover a new biological phenomenon called functional post- transcriptional fragmentation of ncRNAs. Several studies have identified a large set of small ncRNA-derived fragments (sfd-RNA) with a length variation between 16 and 40nt, and which main source are tRNAs and snoRNAs. The interest in sfd-RNA is due to its structural and functional similarity with microRNAs (miRNAs). For example, both types of molecules can
Recommended publications
  • Jeremy Farrar
    FEATURE The BMJ THE BMJ INTERVIEW BMJ: first published as 10.1136/bmj.n459 on 19 February 2021. Downloaded from [email protected] Cite this as: BMJ 2021;372:n459 http://dx.doi.org/10.1136/bmj.n459 Jeremy Farrar: Make vaccine available to other countries as soon as Published: 19 February 2021 our most vulnerable people have received it The SAGE adviser and Wellcome Trust director tells Mun-Keat Looi how the UK government acted too slowly against the pandemic, about the perils of vaccine nationalism, and why he is bullish about controlling covid variants Mun-Keat Looi international features editor “Once the UK has vaccinated our most vulnerable among healthcare workers. We had no human communities and healthcare workers we should make immunity, no diagnostics, no treatment, and no vaccines available to other countries,” insists the vaccines. infectious disease expert Jeremy Farrar. This could Every country should have acted then. Singapore, avert further public health and economic disaster, China, and South Korea did. Yet most of Europe and he says, describing it as “enlightened self-interest, North America waited until the middle of March, and as well as the right ethical thing to do.” that defined the first wave. Countries including the In April 2020, soon after the first UK lockdown began, UK were unwilling to act early, before they felt Farrar predicted that the UK would have one of the comfortable; were unwilling to go deeper than they worst covid-19 death rates in Europe. As a member thought they had to; and were unwilling to keep of the Scientific Advisory Group for Emergencies restrictions in place for as long as was needed.
    [Show full text]
  • Financing Vaccines for Global Health Security
    NBER WORKING PAPER SERIES FINANCING VACCINES FOR GLOBAL HEALTH SECURITY Jonathan T. Vu Benjamin K. Kaplan Shomesh Chaudhuri Monique K. Mansoura Andrew W. Lo Working Paper 27212 http://www.nber.org/papers/w27212 NATIONAL BUREAU OF ECONOMIC RESEARCH 1050 Massachusetts Avenue Cambridge, MA 02138 May 2020 We thank Ellen Carlin, Doug Criscitello, Margaret Crotty, Narges Dorratoltaj, Per Etholm, Jeremy Farrar, Nimah Farzan, Mark Feinberg, Jose-Maria Fernandez, John Grabenstein, Peter Hale, Richard Hatchett, Peter Hotez, Daniel Kaniewski, Adel Mahmoud, Mike Osterholm, May 2020 Farrar, Nimah Kevin Outterson, Chi Heem Wong, CEPI leadership, and two reviewers and the editor for helpful comments and discussion, and Jayna Cummings for editorial assistance. Research support from the MIT Laboratory for Financial Engineering and the Warren Alpert Medical School of Brown University is gratefully acknowledged. The views and opinions expressed in this article are those of the authors only, and do not necessarily represent the views and opinions of any institution or agency, any of their affiliates or employees, any of the individuals acknowledged above, or the National Bureau of Economic Research. Funding support from the MIT Laboratory for Financial Engineering is gratefully acknowledged, but no direct funding was received for this study and no funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of this manuscript. The authors were personally salaried by their institutions during the period of writing (though no specific salary was set aside or given for the writing of this manuscript). At least one co-author has disclosed a financial relationship of potential relevance for this research.
    [Show full text]
  • Oxford Medicine
    Oxford Medicine THE NEWSLETTER OF THE OXFORD MEDICAL ALUMNI OXFORD MEDICINE • DECEMBER 2019 Courtesy of Ludwig Cancer Research of Ludwig Cancer Courtesy The Regius Professor Sir Tingewick is Does reflects on Peter Ratcliffe 80! Developmental 45 years in FRS, Nobel Dyslexia Really medicine Laureate Exist? 2 / OXFORD MEDICINE DECEMBER 2019 President’s Piece Welcome to the December Sir William Osler’s Centenary commemorations will issue of Oxford Medicine, the continue throughout the year in Oxford and beyond. newsletter for Oxford Medical The Osler Club is the first of a number of thriving Alumni (OMA) who have postgraduate Oxford medical societies we plan to feature. trained, taught, or worked at Professor Terence Ryan summarises this year’s five Osler Oxford. Professor John Morris, Club seminars exploring the Oslerian theme ‘For Health OMA president for the past and Wellbeing, Science and Humanities are one’. six years, handed the baton Tingewick is 80 this year. In 2019, as in 1939, Tingewick to me in September. It is a Dr Lyn Williamson, is still the most inclusive Oxford clinical student society. OMA President daunting task to take over from This year, every first year clinical student took part - someone so beloved and so that is 165! The show was a triumph of teamwork and respected, who has taught anatomy to generations talent. The legacy of camaraderie will last a lifetime - as of Oxford students and postgraduates, and shaped witnessed by the 80th anniversary celebrations. Dr Derek the preclinical school for many years. With his Roskell, Senior Tingewick Member for 25 years adds his characteristic kindness and wisdom, he said: ‘You will be fine - and I will be there to advise you’.
    [Show full text]
  • Trustees' Annual Report and Financial Statements 31 March 2016
    THE FRANCIS CRICK INSTITUTE LIMITED A COMPANY LIMITED BY SHARES TRUSTEES’ ANNUAL REPORT AND FINANCIAL STATEMENTS 31 MARCH 2016 Charity registration number: 1140062 Company registration number: 6885462 The Francis Crick Institute Accounts 2016 CONTENTS INSIDE THIS REPORT Trustees’ report (incorporating the Strategic report and Directors’ report) 1 Independent auditor’s report 12 Consolidated statement of financial activities 13 Balance sheets 14 Cash flow statements 15 Notes to the financial statements 16 1 TRUSTEES’ REPORT (INCORPORATING THE STRATEGIC REPORT AND DIRECTORS’ REPORT) The trustees present their annual directors’ report together with the consolidated financial statements for the charity and its subsidiary (together, ‘the Group’) for the year ended 31 March 2016, which are prepared to meet the requirements for a directors’ report and financial statements for Companies Act purposes. The financial statements comply with the Charities Act 2011, the Companies Act 2006, and the Statement of Recommended Practice applicable to charities preparing their accounts in accordance with the Financial Reporting Standard applicable in the UK (FRS102) effective 1 January 2015 (Charity SORP). The trustees’ report includes the additional content required of larger charities. REFERENCE AND ADMINISTRATIVE DETAILS The Francis Crick Institute Limited (‘the charity’, ‘the Institute’ or ‘the Crick) is registered with the Charity Commission, charity number 1140062. The charity has operated and continues to operate under the name of the Francis Crick
    [Show full text]
  • COVID-19 Vaccine Development, Strategy and Implementation
    Symposium: Vaccines and Global Health: COVID-19 Vaccine Development, Strategy and Implementation The Program in Vaccine Education at the Columbia University Vagelos College of Physicians & Surgeons’ mission is to educate medical students and to inform health care professionals, public health experts, academic, government and industry researchers, policy makers, global health non-governmental organizations, journalists, and the general public as to the cutting-edge advances and challenges in modern vaccine development. The Columbia University convenors are Drs. Lawrence Stanberry (Co-Director, PVE), Philip LaRussa (Co-Director, PVE), Wilmot James (Associate Director, PVE), and Marc Grodman (Special Advisor, PVE). We have put together a group of 25 outstanding speakers who have been intimately involved with all aspects of COVID-19 vaccine development, strategy, and implementation. We are delighted to present this five-day virtual symposium at the cusp of the world’s transition to controlling the COVID-19 pandemic. Monday, February 22 National, Regional and Global Response to an Unprecedented Challenge 12:00-12:10 Welcome: Lee Bollinger, JD – President, Columbia University 12:10-12:15 Moderator: Lawrence R. Stanberry, MD, PhD – Director of the Programs in Global Health, Columbia University Vagelos College of Physicians and Surgeons 12:15-12:45 Keynote: Sir Jeremy Farrar, BSc, MBBS, PhD – Director, Wellcome Trust The Role of the Wellcome Trust in COVID-19 Vaccine Preparedness 12:45-1:30 Speakers: - Shabir Madhi, MBChB, MMed, FCPaeds PhD – Professor of Vaccinology, University of the Witwatersrand – A South African perspective on vaccine preparedness and availability. - Nancy Messonnier, MD – Director, National Center for Immunization and Respiratory Diseases, US CDC – A US CDC perspective on vaccine preparedness and availability.
    [Show full text]
  • Meeting Schedule/Structure
    Special isirv-AVG Virtual Conference on ‘Therapeutics for COVID-19’ Tuesday 6th - Thursday 8th October 2020 (12.00-16.00 GMT daily) Programme Tuesday 6 October 12:00-12:15 Welcome Alan Hay, Francis Crick Institute, London, UK & Frederick Hayden, University of Virginia School of Medicine, Charlottesville, VA, USA Introduction Jeremy Farrar, Wellcome Trust, London, UK Chairs TBC 12:15-12:40 COVID-19 Clinical Spectrum, Complications, and Coinfections Bin Cao, China-Japan Friendship Hospital, Beijing, China 12:40-13:00 COVID-19 Viral Replication Kinetics Malik Peiris, University of Hong Kong, HK SAR, China 13:00-13:20 COVID-19 Autopsy Findings Xiuwu Bian, China (TBC) 13:20-13:40 Immunopathogenesis of COVID-19 Peter Openshaw, Imperial College London, UK 13:40-14:00 Pathogenesis and Management of ARDS – Richard Wunderink, Northwestern University, Evanston, IL, USA 14:00-14:10 Comfort Break 14:10-15:10 Chairs TBC Oral Abstract Session 1 4 x 15 minute presentations (including Q&A) 15:10-15:20 Close of Day 1 Poster Viewing Page 1 of 3 Wednesday 7 October Chairs TBC 12:00-12:20 SARS-CoV-2 Antiviral Targets Mark Denison (accepted in principle) 12:20-12:40 Pre-clinical Models for Downselecting Candidates Andres Pizzorno, International Center for Research in Infectious Diseases, Lyon, France 12:40-13:10 RECOVERY Trial and Strategies for Rapid Clinical Testing Peter Horby, Oxford, UK 13:10-13:30 Convalescent Plasma and Polyclonal Antibodies - Michael Joyner, Mayo Clinic, MN, USA 13:30-13:50 Monoclonal Antibodies Erica Saphire, La Jolla Institute for
    [Show full text]
  • World Economic Forum Annual Meeting 2017 Programme
    Global Agenda World Economic Forum Annual Meeting 2017 Programme Davos-Klosters, Switzerland 17-20 January Programme Pillars Programme Icons Programme Co- Chairs Experience Webcast Session Frans van Houten, President and Chief Executive Officer, Royal Philips, Netherlands Immersive experiences across time, space and emotions made memorable by Interpretation Brian T. Moynihan, Chairman of the inspiring interactions and thought- Board and Chief Executive Officer, provoking settings On the record Bank of America Corporation, USA Sharmeen Obaid-Chinoy, Discover Sign-up required Documentary Filmmaker, SOC Films, Pakistan; Young Global Leader Engaging explorations of the conceptual breakthroughs of our time and their Helle Thorning-Schmidt, Chief transformative impact on society, industry Executive Officer, Save the Children and policy International, United Kingdom Meg Whitman, President and Chief Debate Executive Officer, Hewlett Packard Enterprise, USA Insightful exchanges bringing together diverse opinions and ideas on today's most relevant economic, scientific and political issues Collaborate Hands-on sessions where leaders from all backgrounds come together to shape solutions to the world's most pressing challenges World Economic Forum Annual Meeting 2017 - Programme 2 Sunday 15 January 06.00 - 01.00 Registration - Mühlestrasse 6 - 7260 Davos Dorf 1 registration Registration Opens Pick up your badge as of Sunday 15 January at 06.00 at Registration located at Mühlestrasse 6. Please note that the Congress Centre opens on Monday 16 January
    [Show full text]
  • Research Bodies Vow to Share Data on Zika
    BMJ 2016;352:i877 doi: 10.1136/bmj.i877 (Published 11 February 2016) Page 1 of 1 News BMJ: first published as 10.1136/bmj.i877 on 11 February 2016. Downloaded from NEWS Research bodies vow to share data on Zika Zosia Kmietowicz The BMJ Academic journals, charities, research funders, and institutes available to all, free of charge, as soon as is feasibly possible. have committed themselves to sharing data and results relevant Journal signatories have said that doing this would not preclude to the current Zika virus outbreak and future public health researchers from subsequently publishing papers in their titles. emergencies as rapidly and openly as possible. Jeremy Farrar, director of the Wellcome Trust and a signatory The organisations, including the Bill and Melinda Gates to the statement, said, “Research is an essential part of the Foundation, Médecins Sans Frontières, the US National response to any global health emergency. This is particularly Institutes of Health, and the UK health research charity the true for Zika, where so much is still unknown about the virus, Wellcome Trust, along with leading academic journals such as how it is spread, and the possible link with microcephaly. The BMJ, Nature, Science, and the New England Journal of “It’s critical that as results become available they are shared Medicine, have signed a joint declaration and hope that other rapidly in a way that is equitable, ethical, and transparent. This bodies will add their names to the statement in the coming will ensure that the knowledge gained is turned quickly into weeks. health interventions that can have an impact on the epidemic.” The statement is intended to ensure that any information that http://www.bmj.com/ might have value in combating the Zika outbreak is made on 27 September 2021 by guest.
    [Show full text]
  • Drug Development for Neglected Tropical Diseases: Dndi and the Product Development Partnership (PDP) Model
    Drug Development for Neglected Tropical Diseases: DNDi and the Product Development Partnership (PDP) Model Julia Tuttle A thesis submitted to the Department of Global Health for honors Duke University Durham, North Carolina 2016 Drug Development for Neglected Tropical Diseases Julia Tuttle Table of Contents Abstract 3 Introduction 1. Background 1.1 Economics of Drug Development 1.2 NTDs: The remaining market failure 2. Exploring Solutions 2.1 Theories of Alternative Policy Action 2.2 Public-Private Partnerships 3. Case Study: DNDi 3.1 Organizational Overview 3.2 Therapeutic Advancements 3.3 Pipeline Progress 3.4 Current Operations 3.4.1 Target Product Profiles 3.4.2 Clinical Trial Platforms 3.4.3 Developing Drug Screens 3.4.4 Drug Discovery 3.4.5 Demonstration Project 3.4.6 Advocacy 4. Conclusion 4.1 Summary of DNDi 4.2 Analysis of Strengths Independence Health Systems Strengthening and Technical Capacity Technology Transfer Openness and Access Breadth of Impact Strong Partnerships Cost-efficiency 4.3 Analysis of Weaknesses Financial Limitations Political Context New Obstacles Moving Forward 4.4 Final Remarks Appendix 1- Chart of Product Development Partnerships (PDPs) Appendix 2- DNDi Organizational Overview Appendix 3- DNDi Demonstration Project Graphic Overview Appendix 4- List of DNDi Partners and Funders 2 Drug Development for Neglected Tropical Diseases Julia Tuttle Abstract Neglected tropical diseases (NTDs), including leishmaniasis, Chagas disease, sleeping sickness, dengue fever, and schistosomiasis to name a few, are endemic in 149 countries and impact 1.4 billion people- often the most vulnerable groups in the poorest countries (WHO 2016). Unfortunately, many of these diseases have no vaccines to prevent them, nonexistent or incredibly problematic treatments, and limited resources dedicated to monitoring, controlling, and improving the situation of those who are infected.
    [Show full text]
  • Auf Der Suche Nach Der Verlorenen Zeit
    © Jahrbuch des Vereins zum Schutz der Bergwelt (München), 85. Jahrgang 2020, S. 223–308 Auf der Suche nach der verlorenen Zeit. Was zu Beginn der Coronakrise versäumt worden ist und was wir daraus für die Klima- und Biodiversitätskrise lernen können. Ein Denkanstoß von Rudi Erlacher Keywords: Corona-Pandemie, Klima- und Biodiversitätskrise, Weltrisikogesellschaft, Krisenkultur, Ausnahmezustand Die Covid-19-Pandemie erschüttert die Welt. Nach dem Ausbruch des Virus im Januar 2020 in China, kam es im März/April 2020 im Westen zu einer ersten Infektionswelle. Mit einer drastischen Vorsorgepolitik mit Einschränkungen der Bewegungsfreiheit (Lockdown) akzeptierte man einen massiven wirtschaftlichen Einbruch. Die Politik zeigte einen Mut, der beispielgebend sein könnte gegen die Biodiversitäts- und die Klimakrise. Eine Analyse der Pandemie bis zur Ausrufung des „Ausnahmezustands“ durch den französischen Präsidenten Emmanuel Macron und die deutsche Bundeskanzlerin Angela Merkel (16.3. bzw. 18.3.2020) zeigt aber, dass zu Beginn entscheidende Fehler gemacht wurden. Man ließ das Virus bis ca. Mitte März gewähren. Entschlossen gehandelt wurde erst mit den Toten in Italien. Diese Verzögerung hatte ihren Grund in einer Krisenkultur, die verhaltensökonomisch orientiert, den Menschen in der Krise als hyperemotional und irrational deutet. Eine Risikovorsor- ge, die mit einem „Worst-Case“ kalkulieren müsste, war damit Tabu. Das hätte einen „globalen coronaviralen Angststurm“ provozieren können – so aber konnte man die eigene Taten losigkeit exkulpieren. Das Virus traf dann den Westen wie aus heiterem Himmel. Der Verlauf der Pandemie ist lehrreich. Seit Jahren engagiert sich der VzSB für ein ent- schiedeneres Handeln in der Biodiversitäts- und Klimakrise. Nun ergeben sich Hinweise, dass eine zur Pandemie analoge Krisenkultur zur Lähmung insbesondere in der Klima- krise führt: Eine „Apokalypsebremse“ in Berichterstattung und Politik soll verhindern, dass die Menschen von den Tatsachen überfordert werden und in ihrem Engagement gegen die Krisen nicht ermatten.
    [Show full text]
  • A Map of the Alternative Biomedical R&D Landscape
    A map of the alternative biomedical R&D landscape ACKNOWLEDGEMENTS We would like to acknowledge all the engaged and active student leaders in UAEM who have supported, participated and activated around the critical global health issue of alternative biomedical R&D, the role of universities and ensuring access to medicines for all. Thanks as well as to the staff and board of UAEM. Special thanks to Els Torreele PhD, Director of the Open Society Public Health Program’s Access to Essential Medicines Initiative, for her advice, support and encouragement. And thanks to the team at signals.ca for providing us with their design talent and enthusiastically agreeing to complete this project in record time! AUTHOR BIOGRAPHIES Rachel Kiddell-Monroe LL.M is a humanitarian, a lawyer and an activist. She is Special Adviser to Universities Allied for Essential Medicines (UAEM) and served 6 years as President of the UAEM board of directors. She is also a member of the International Board of directors for Médecins Sans Frontières/Doctors Without Borders (MSF). She lives in Montreal and has worked in south east Asia with human rights and environmental grassroots activists as well as with MSF in Djibouti, Rwanda, the Democratic Republic of Congo and throughout Latin America. Rachel has also served as the Canadian director of MSF’s Access to Medicines Campaign. Rachel sits on the board of UAEM Europe, on the Advisory Council of UAEM Brazil and the board of the Young Professionals for Chronic Disease Network. Rachel is a Professor of Practice at McGill University, lectures on international development and is part of the Adult Clinical Ethics Committee at McGill University Health Centres.
    [Show full text]
  • Jeremy Farrar
    Jeremy farrar It is a great privilege and honor to present this ESICM citation Despite his numerous commitments, Jeremy Farrar remains of Honorary Membership to Professor Jeremy Farrar. Jeremy a very approachable clinician, who conducts daily clinical ward Farrar is an outstanding clinical scientist who has built a rounds in a hospital that provides care for several thousand reputation as one of the world's leading figures in the field of patients each year. He has established an extensive training infectious disease. He is Professor of Tropical Medicine and programme, which includes schools, undergraduate bSc and global Health at Oxford university, adjunct Professor at the MD students from asia and Latin america, through Masters, NuS of Singapore, global Scholar at Princeton university and PhD and post-doctoral opportunities for both scientists Director of the Wellcome Trust's Major Overseas Programme and clinicians. His career demonstrates a battle against in vietnam. Since October 1st, he has just joined the Wellcome the arbitrary and often damaging compartmentalisation of Trust to become its new Director. clinical medicine, basic science and public health, as he builds bridges across borders and with society at a time of increasing Professor Jeremy Farrar trained in Neurology in London, globalisation. Edinburgh, Melbourne and Oxford. He obtained a PhD in Immunology from Oxford university and uCSF, uSa. Since 1996, On a more personal standpoint, Professor Farrar is an he has been the Director of the Clinical Research unit in Ho Chi accomplished alpinist, who also plays rugby, cricket and Minh City (vietnam). From this hub, he has developed research hockey.
    [Show full text]