DOCSLIB.ORG

Department of Computational and Systems Biology Department of COMPUTATIONAL & SYSTEMS BIOLOGY

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Department of Computational and Systems Biology Department of COMPUTATIONAL & SYSTEMS BIOLOGY Annual Report, FY16 2 Department of Computational and Systems Biology Department of COMPUTATIONAL & SYSTEMS BIOLOGY School of Medicine University of Pittsburgh Ivet Bahar, Ph.D. Distinguished Professor and John K. Vries Chair Fiscal Year 2016 Section I : General Description (Activities and Mission) 4 Section II : Research and Other Scholarly Activities 9 Section III : Teaching Activities 64 Section IV : Faculty Data 78 Section V : Three-Year Bibliography 92 Section VI : Financial Plan for Fiscal Year 2016 118 (2001-2016) Annual Report, FY16 Department of Computational and Systems Biology 3 Section I General Description Computational and Systems Biology – Who We Are The Department of Computational and Systems Biology (CSB) has continued to be a leader in the field. Our increasing focus on multi-scale interactions in biological systems enabled us to tackle more research at an integrated, Systems level. The post-genomic and big data era has brought a new excitement to science. With this excitement also comes new challenges that require new and innovative approaches with which to tackle them. CSB continues to play a leading role in driving discovery through continued interdisciplinary efforts to answer the research challenges of today and define the new approaches to address the questions of tomorrow. Concomitant, with our research foci, we also make concerted efforts in educating the next generation of scientists, who will continue this work. The unique, hands-on research opportunities that we provide to students at the graduate, undergraduate, and even high school levels provide these students with the necessary interdisciplinary and hands-on training to prepare them for careers in these fields. At the same time, these efforts provide numerous opportunities for our postdoctoral fellows and junior faculty to serve as mentors for our scientists-in-training, especially those at the undergraduate and high school level. These early experiences in mentoring are valuable opportunities that allow these scientists to hone their mentoring skills, while working together with some of the best and brightest in the next generation. A Brief History Computational biology was established as a research discipline at the University of Pittsburgh with the vision of the Senior Vice Chancellor, Dr. Arthur S. Levine, who recruited Dr. Bahar to create a new Center for Computational Biology and Bioinformatics in March 2001, which soon became a highly visible center. The creation of the Department of Computational Biology within the School of Medicine followed in October 2004. Built on the premise of the founding Center for Computational Biology and Bioinformatics, the department was created with Dr. Ivet Bahar as the Founding Chair, to establish a home uniquely welcoming to highly interdisciplinary faculty, and to firmly establish the University of Pittsburgh in a nationally recognized leadership role in a field of tremendous growth and excitement. The department name was changed to Department of Computational and Systems Biology in 2009, to reflect the expansion in research and educational goals and activities of the department. In 2016, the contributions of our Faculty were highlighted by various awards and promotions. Within our department: Dr. Panagiotis Benos was promoted to Professor; Jianhua Xing was promoted to Associate Professor with Tenure; S. Chakra Chennubhotla was promoted to Associate Professor with Tenure; Dr. Joseph Ayoob was promoted to Associate Professor; Dr. Bing Liu was promoted to Research Assistant Professor; Dr. Anne-Ruxandra Carvunis was recruited as an Assistant Professor in the Tenure stream and will join the department in October; and Dr. Zuckerman was selected as the 2015-2016 DISTINGUISHED MENTOR in the School of Medicine. Dr. Clark was featured in Pitt Med highlighting his work in gene evolution and the Center for Causal Discovery (PI: Cooper, Bahar and Berg) was the cover story for the Winter 2016 issue. Dr. Jeremy Berg will be reducing his role in the Department as he moves on taking the position of Editor in Chief of Science for a 5-year term. Dr. Berg is the 20th Editor in Chief since the journal’s inception in 1880. We are committed to providing a home that welcomes highly interdisciplinary faculty, and that firmly establishes the University of Pittsburgh in nationally recognized leadership roles in rapidly growing and evolving fields that are driving the next wave of scientific discovery. CSB Research – Leading the Field with Cutting-edge Science Increasingly complex biological problems and extremely large biological data sets have necessitated new approaches to answer many of today’s current research challenges. As one of the fields in what are now being called the “New Biologies”, Computational and Systems Biology encompasses an interdisciplinary approach to harness the power of computation to tackle the emerging big data challenges and to answer questions in biology not amenable to traditional approaches. Thus, to rise to these challenges and to continue to be a leader in this newly emerging field, CSB has set our research mission to: Advance the scientific understanding of biological systems through computational tools and theoretical approaches based on the fundamental principles of physical sciences. Annual Report, FY16 4 Department of Computational and Systems Biology Design new computational/mathematical models and methods for simulating complex biological processes and for extracting useful information from accumulating data. CSB investigators pursue this mission by investigating leading questions in biology and medicine in four major areas of specialization/growth in the field: 1. Bioinformatics and Computational Genomics and Proteomics 2. Cell and Systems Biology 3. Molecular Structural Biology 4. Pharmacology and Drug Discovery Bioinformatics and Computational Genomics and Proteomics The genomics and proteomics fields are primarily based on computer science and statistics and aim to digest the daunting quantity of “-omics” data now available by systematic development and application of probability and statistics theories, information technologies and data mining techniques. Within Genomics there are three main categories: functional genomics, structural genomics, and comparative genomics. Functional genomics generally refers to the high throughput determination of gene functions. Structural genomics is the systematic effort to gain a complete structural description of a defined set of molecules, ultimately for an organism’s entire proteome. Comparative genomics uses evolutionary relationships between various organisms to understand the structure and function of the genome. Proteomics aims at quantifying the expression levels of the complete protein complement (the proteome) in a cell at any given time. While proteomics research was initially focused on two-dimensional gel electrophoresis for protein separation and identification, proteomics now refers to any procedure that characterizes the function of large sets of proteins. Proteomics may be considered as a subset of functional genomics. Cell and Systems Biology Systems biology seeks to integrate different levels of information to understand how biological systems function at multiple scales, with the goal of developing an understandable model of a whole system. This is accomplished by studying the relationships and interactions between various parts of the particular system of interest, which could range over orders of magnitude, from molecular assemblies to subcellular -, multicellular-, and tissue-level systems. Molecular Structural Biology Studying the architecture, shape, and dynamics of biological macromolecules is paramount to understanding the basic mechanisms that drive the essential processes of all life. Macromolecules such as proteins and nucleic acids carry out most of the functions of a cell, and are able to perform these functions by adopting ensembles of structures under native state conditions. Structural biology is concerned with the driving forces and interactions that determine the three-dimensional shapes and dynamics of biomolecules. Moreover, by applying the fundamental principles of the physical sciences, we are beginning to establish sequence-structure-dynamics-function relationships that enable deeper levels of discoveries, and summon the possibility of de novo structural and functional predictions at the proteome level. Pharmacology and Drug Discovery Computational and theoretical approaches are revolutionizing Pharmacology and Drug Discovery. Predicting, modeling, and simulating potential therapeutic agents and their interactions with target molecules is a powerful new first step in the drug discovery process. This in silico approach streamlines the often laborious, expensive, and slow process of identifying and testing lead compounds for use as treatments. Combining these advances with high-throughput and high-content cellular- and systems- level pharmacological and poly-pharmacological approaches is profoundly impacting medical science. The UPDDI is committing major efforts in "Quantitative Systems Pharmacology" (QSP) alongside "Chemistry and Molecular Biophysics", while all technical areas of drug discovery and development will continue to be employed and extended in our programs. While the four areas may appear distinct, there is considerable overlap, and they all share a common goal: quantitative evaluation/prediction of biological data/processes. Traditionally, these areas have been advanced by researchers specialized
Load more

Recommended publications
  • Opportunities and Challenges in Phenotypic Drug Discovery: an Industry Perspective
    PERSPECTIVES Nevertheless, there are still challenges in OPINION prospectively understanding the key success factors for modern PDD and how maximal Opportunities and challenges in value can be obtained. Articles published after the analysis by Swinney and Anthony have re-examined the contribution of PDD phenotypic drug discovery: an to new drug discovery6,7 and have refined the conditions for its successful application8. industry perspective Importantly, it is apparent on closer examination that the classification of drugs John G. Moffat, Fabien Vincent, Jonathan A. Lee, Jörg Eder and as ‘phenotypically discovered’ is somewhat Marco Prunotto inconsistent6,7 and that, in fact, the majority of successful drug discovery programmes Abstract | Phenotypic drug discovery (PDD) approaches do not rely on knowledge combine target knowledge and functional of the identity of a specific drug target or a hypothesis about its role in disease, in cellular assays to identify drug candidates contrast to the target-based strategies that have been widely used in the with the most advantageous molecular pharmaceutical industry in the past three decades. However, in recent years, there mechanism of action (MoA). Although there is clear evidence that phenotypic has been a resurgence in interest in PDD approaches based on their potential to screening can be an attractive proposition address the incompletely understood complexity of diseases and their promise for efficiently identifying functionally of delivering first-in-class drugs, as well as major advances in the tools for active hits that lead to first-in-class drugs, cell-based phenotypic screening. Nevertheless, PDD approaches also have the gap between a screening hit and an considerable challenges, such as hit validation and target deconvolution.
    [Show full text]
  • Current Screening Methodologies in Drug Discovery for Selected Human Diseases
    marine drugs Review Current Screening Methodologies in Drug Discovery for Selected Human Diseases Olga Maria Lage 1,2,*, María C. Ramos 3, Rita Calisto 1,2, Eduarda Almeida 1,2, Vitor Vasconcelos 1,2 ID and Francisca Vicente 3 1 Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/nº 4169-007 Porto, Portugal; [email protected] (R.C.); [email protected] (E.A.); [email protected] (V.V.) 2 CIIMAR/CIMAR–Centro Interdisciplinar de Investigação Marinha e Ambiental–Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal 3 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain; [email protected] (M.C.R.); [email protected] (F.V.) * Correspondence: [email protected]; Tel.: +351-22-0402724; Fax.: +351-22-0402799 Received: 7 August 2018; Accepted: 11 August 2018; Published: 14 August 2018 Abstract: The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered.
    [Show full text]
  • An Emerging Strategy for Rapid Target and Drug Discovery
    R E V I E W S CHEMOGENOMICS: AN EMERGING STRATEGY FOR RAPID TARGET AND DRUG DISCOVERY Markus Bredel*‡ and Edgar Jacoby§ Chemogenomics is an emerging discipline that combines the latest tools of genomics and chemistry and applies them to target and drug discovery. Its strength lies in eliminating the bottleneck that currently occurs in target identification by measuring the broad, conditional effects of chemical libraries on whole biological systems or by screening large chemical libraries quickly and efficiently against selected targets. The hope is that chemogenomics will concurrently identify and validate therapeutic targets and detect drug candidates to rapidly and effectively generate new treatments for many human diseases. Over the past five decades, pharmacological compounds however, that owing to the emergence of various sub- TRANSCRIPTIONAL PROFILING The study of the transcriptome have been identified that collectively target the products specialties of chemogenomics (discussed in the next — the complete set of RNA of ~400–500 genes in the human body; however, only section) and the involvement of several disciplines, it is transcripts that are produced by ~120 of these genes have reached the market as the tar- currently almost impossible to give a simple and com- the genome at any one time — gets of drugs1,2. The Human Genome Project3,4 has mon definition for this research discipline (BOX 1). using high-throughput methods, such as microarray made available many potential new targets for drug In chemogenomics-based drug discovery, large col- analysis. intervention: several thousand of the approximately lections of chemical products are screened for the paral- 30,000–40,000 estimated human genes4 could be associ- lel identification of biological targets and biologically ated with disease and, similarly, several thousand active compounds.
    [Show full text]
  • Council for Scientific and Industrial Research
    ANNUAL 2018/19 PO Box 395, Pretoria, 0001, South Africa Published by: CSIR Communication Enquiries: Tel +27 12 841 2911 • Email: [email protected] ISBN-13 978-0-7988-5643-0 “The objects of the CSIR are, through directed and particularly multi-disciplinary research and technological innovation, to foster, in the national interest and in fields which in its opinion should receive preference, industrial and scientific development, either by itself or in co-operation with principals from the private or public sectors, and thereby to contribute to the improvement of the quality of life of the people of the Republic, and to perform any other functions that may be assigned to the CSIR by or under this Act.” (Scientific Research Council Act 46 of 1988, as amended by Act 27 of 2014) CONTENTS The CSIR at a glance ......................................................2 From our leadership .......................................................6 Organisational highlights .............................................. 24 Financial sustainability and governance .......................... 66 Executive report ........................................................... 87 Consolidated financial statements ................................ 101 Knowledge dissemination ............................................ 148 Abbreviations ............................................................ 175 1 INTRODUCTION THE CSIR AT A GLANCE 2 342 TOTAL STAFF BASE 1 608 1 610 1 041 *SET BASE BLACK SOUTH FEMALE SOUTH AFRICANS AFRICANS *Science, engineering and technology
    [Show full text]
  • High Content Phenotypic Profiling in Oesophageal Adenocarcinoma Identifies Selectively
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.20.912212; this version posted January 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. High Content Phenotypic Profiling in Oesophageal Adenocarcinoma Identifies Selectively Active Pharmacological Classes of Drugs for Repurposing and Chemical Starting Points for Novel Drug Discovery Rebecca E Hughes1, Richard J R Elliott1, Alison F Munro1, Ashraff Makda1, J Robert O’Neill2, Ted Hupp1, Neil O Carragher1 Affiliations 1MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XR 2Cambridge Oesophagogastric Unit, Cambridge University Hospitals Foundation Trust, Cambridge, CB2 2QQ. Corresponding Author: Professor Neil Carragher Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR United Kingdom Email: [email protected] Keywords: Oesophageal Adenocarcinoma, Phenotypic, High-content, Mechanism-of- Action, Machine Learning bioRxiv preprint doi: https://doi.org/10.1101/2020.01.20.912212; this version posted January 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Oesophageal adenocarcinoma (OAC) is a highly heterogeneous disease, dominated by large-scale genomic rearrangements and copy number alterations. Such characteristics have hampered conventional target-directed drug discovery and personalized medicine strategies contributing to poor outcomes for patients diagnosed with OAC.
    [Show full text]
  • Improving Impact Through Licensing and Ventures FOREWORD
    ScienceScopewww.csir.co.za PUBLICATION OF THE CSIR | VOLUME 6 | NUMBER 3 | FEBRUARY 2013 SOUTH AFRICA’S COUNCIL FOR SCIENTIFIC AND INDUSTRIAL RESEARCH Improving impact through licensing and ventures FOREWORD THE CSIR’S OPERATING UNITS, NATIONAL RESEARCH CENTRES AND SERVICES Improving impact through licensing > CSIR Biosciences Pretoria 012 841-3260 > CSIR Built Environment and venture creation Pretoria 012 841-3871 Stellenbosch 021 888-2508 > CSIR Defence, Peace, Safety Beyond the CSIR’s significant contribution to the global knowledge base, we are determined to ensure and Security that our work has quantifiable economic, environmental and social benefits. One of the ways to attain Pretoria 012 841-2780 > CSIR Materials Science and this is to improve our transfer of technology and innovations to third parties. Manufacturing Pretoria 012 841-4392 We recognise that innovation have arisen from the collective There are many examples of to national imperatives such CSIR Licensing and ventures Johannesburg 011 482-1300 implies dissemination and efforts of our multidisciplinary technologies and services with as the creation of decent Port Elizabeth 041 508-3200 Pretoria 012 841 4212 [email protected] uptake and that for an invention competence base. In all of these CSIR roots that have been employment through inclusive Cape Town 021 685-4329 to become an innovation, it cases the technology readiness transformed as technologies economic growth, poverty > CSIR Modelling and Digital Science needs to be implemented or is at an advanced stage. In some merged and grew. The CSIR reduction and the development Compiled by Pretoria 012 841-3298 used by the market and society.
    [Show full text]
  • High Throughput Rna Interference Based Screen for the Identification of Genes Implicated in Listeria Monocytogenes Infection
    HIGH THROUGHPUT RNA INTERFERENCE BASED SCREEN FOR THE IDENTIFICATION OF GENES IMPLICATED IN LISTERIA MONOCYTOGENES INFECTION By Student: Asongwe Lionel Ateh Tantoh Student number: TNTASO001 Thesis Presented for the Degree of DOCTOR OF PHILOSOPHY In the Department of Medicine UNIVERSITYTown OF CAPE TOWN FEBRUARY 2014 SupervisorsCape of Prof. FRANK BROMBACHER Division of Immunology, Institute of Infectious Diseases and Molecular Medicine & International Centre for Genetic Engineering and Biotechnology (ICGEB) University of Cape Town Medical School. 7925 University Dr. NEIL EMANS Persomics (PTY) LTD, Barinor’s Vineyards North. The vineyards office Etate, 99 Jip de Jager. 7530 The copyright of this thesis vests in the author. No quotation from it or information derived from it is to be published without full acknowledgementTown of the source. The thesis is to be used for private study or non- commercial research purposes only. Cape Published by the University ofof Cape Town (UCT) in terms of the non-exclusive license granted to UCT by the author. University DEDICATION This thesis is primarily dedicated to the Almighty God for the strength, comfort, protection and the uncounted blessings He showered upon my feeble shoulders during this period. This thesis is also dedicated to my parents; Monica Mangwi Tantoh and Sylvester Tantoh who through their relentless moral support, incredible motivation and inspiration and financial support, I was able to accomplish this difficult journey. Also, this thesis is dedicated to my late grandmother mama Beatrice Nanga Asongwe, who once said to me, “Life is a battlefield and as long as we are alive, we have to keep fighting”. Finally, I dedicate this thesis to my siblings, Doris, Clarisse, Valerie, Ferdinand, Jervis, Kelly, Ateh and to my nephew and nieces Lionel, Pashukeni, Titi and Ngwe for all the joy they brought into my life during this period.
    [Show full text]
  • Seventy Years
    ScienceScope SCIENCESCOPE | VOLUME 8 | NUMBER 2 OF 2015 SOUTH AFRICA’S COUNCILFORSCIENTIFICANDINDUSTRIALRESEARCH SOUTH AFRICA’S OFTHECSIR|VOLUME8NUMBER2 PUBLICATION 1959 1962 1963 1965 1967 SEVENTY YEARS 1970 1979 1981 1982 1997 1999 2001 WORK IDEAS THAT 2003 2009 OF 2 IN TE 2015 RN A T I O N A L Y E A R O F L I G H 15 T CSIR UNITS > CSIR Biosciences Pretoria 012 841-3260 > CSIR Built Environment Pretoria 012 841-3871 Stellenbosch 021 888-2508 > CSIR Defence, Peace, Safety and Security Pretoria 012 841-2780 > CSIR Materials Science and Manufacturing Pretoria 012 841-4392 Cover artwork: Sizakele Shingange Johannesburg 011 482-1300 Port Elizabeth 042 508-3200 Cape Town 021 685-4329 > CSIR Meraka Institute Pretoria 012 841-3028 Cape Town (Centre for High Performance Computing) 021 658-2740 > CSIR Modelling and Digital Science Pretoria 012 841-3298 > CSIR National Laser Centre Pretoria 012 841-4188 > CSIR Natural Resources and the Environment Pretoria 012 841-4005 Stellenbosch 021 658-2766 Durban 031 242-2300 Pietermaritzburg 033 260-5446 Nelspruit 013 759-8036 > CSIR Implementation Unit Pretoria 012 841 3332 Stellenbosch 021 658 6582/2776 Cape Town 021 658 2761 Port Elizabeth 041 508 3220 Durban 031 242 2441/2300/2393 Cottesloe 011 482 1300 Kloppersbos 012 841 2247 Compiled by CSIR Strategic Communication [email protected] Photography Kaimara Shutterstock Printed on Hansol Hi Q TitanTM art paper. Manufactured from TCF (Totally Chlorine Design and production Free) and ECF (Elemental Chlorine Free) pulp. Only wood from sustainable forests Creative Vision – 082 338 3742 is used.
    [Show full text]
  • Disruptive Approaches to Accelerate Drug Discovery and Development
    Business Dis rupti ve approac hes to acce lerate drug disco very and develop ment part 1: tools, tec hnolo gies and t he c ore model Tesla intends to implement and practise an ‘open source’ philosophy to its large patent portfolio and claims it would not pursue any legal action against anyone using them in good faith. This is a hard pill to swallow for the industry at-large. But, the pharmaceutical industry ought to seriously consider such an inclusive strategy to enhance the pace of drug discovery and development for the benefit of humanity’s welfare. he staggering failure rate of experimental content; Alibaba, the world’s most valuable retail - By Ibis Sánchez- drugs in clinical trials indicates that er owns no inventory; and Airbnb, the world’s Serrano, T despite huge investments in novel tech - largest hotelier, owns no real estate. Most recently, Dr Tom Pfeifer nologies, productivity gains in the pharmaceutical three large US corporations, Amazon, Berkshire and Dr Rathnam industry remain elusive. The pharmaceutical Hathaway and JPMorgan Chase, have announced Chaguturu industry is facing a serious innovation deficit. The the formation of an independent healthcare com - current biopharma model is therefore unsustain - pany for their employees in the United States to able and disruptive approaches are needed to rem - deal with the soaring cost of health insurance pre - edy the status quo. It is incumbent upon the miums and pharmaceuticals. In ‘The Evolution of biomedical research community to harness the collective intelligence of pharma, biotech, academia, governmental agencies, non-profit research foundations and patient advocacy groups “Tesla Motors was created to accelerate the advent of to accelerate innovation.
    [Show full text]
  • How Polypharmacologic Is Each Chemogenomics Library?
    Research Article For reprint orders, please contact: [email protected] How polypharmacologic is each chemogenomics library? Eric Ni1,2,3, Eehjoe Kwon1, Lauren M. Young2, Klara Felsovalyi2, Jennifer Fuller2 & Timothy Cardozo*,1 1NYU Langone Health, Department of Biochemistry & Molecular Pharmacology, New York, NY 10016, USA 2Genecentrix Inc, New York, NY 10014, USA 3Yale University, Department of Computational Biology & Bioinformatics, New Haven, CT 06520, USA *Author for correspondence: [email protected] Aim: High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a ‘polypharmacology index’ for broad chemogenomics screening libraries. Methods: All known targets of all the compounds in each library were plotted as a histogram and fitted to a Boltzmann distribution, whose linearized slope is indicative ofthe overall polypharmacology of the library. Results & conclusion: Comparison of libraries clearly distinguished the most target-specific library, which might be assumed to be more useful for target deconvolution ina phenotypic screen. First draft submitted: 28 October 2019; Accepted for publication: 16 December 2019; Published online: 5 February 2020 Keywords: chemogenomics • polypharmacology • target deconvolution High-throughput phenotypic screening (pHTS) is defined as direct application of perturbagens (usually drug-like small molecule compounds) to complex biological systems that exhibit complex phenotypes (usually cells, but commonly organoids and animals as well) [1]. This approach is based on the prioritization of drug candidate cellular bioactivity over drug mechanism of action (MoA).
    [Show full text]
  • "Microscopy and Image Analysis"
    Microscopy and Image Analysis UNIT 4.4 George McNamara,1 Michael Difilippantonio,2 Thomas Ried,3 and Frederick R. Bieber4 1Biomedical Consultant, Baltimore, Maryland 2Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 3Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 4Brigham and Women’s Hospital, Boston, Massachusetts This unit provides an overview of light microscopy, including objectives, light sources, filters, film, and color photography for fluorescence microscopy and fluorescence in situ hybridization (FISH). We believe there are excellent oppor- tunities for cytogeneticists, pathologists, and other biomedical readers, to take advantage of specimen optical clearing techniques and expansion microscopy— we briefly point to these new opportunities. C 2017 by John Wiley & Sons, Inc. Keywords: light microscopy r digital imaging r fluorescence in situ hybridiza- tion r functional genomics How to cite this article: McNamara, G., Difilippantonio, M., Ried, T., & Bieber, F. R. (2017). Microscopy and image analysis. Current Protocols in Human Genetics, 94, 4.4.1–4.4.89. doi: 10.1002/cphg.42 INTRODUCTION by Ishikawa-Ankerhold, Ankerhold, & Drum- This unit provides an overview of light mi- men (2012), and Liu, Ahmed, & Wohland croscopy, including objectives, light sources, (2008). Scanning and transmission electron filters, and imaging for fluorescence mi- microscopy as well as confocal microscopy croscopy and fluorescence in situ hybridiza- and multi-photon excitation microscopy are tion (FISH). We encourage thinking outside not covered in this unit despite their useful- the usual magnification range of 10× to ness as invaluable tools for contemporary stud- 100× objective lenses, by ranging from sin- ies of biological systems; see Diaspro, 2001; gle molecules to whole mice and humans.
    [Show full text]
  • Register by June 12 and Save up to $600
    REGISTER BY JUNE 12 AND SAVE UP TO $600 Organized by Cambridge Healthtech The Industry’s Preeminent Event on Novel Drug Targets Institute 13th Annual September 21-24, 2015 Westin Boston Waterfront | Boston, MA SEPTEMBER 22 - 23 SEPTEMBER 23 - 24 n Targeting Epigenetic Readers and Chromatin Remodelers n Targeting Histone Methyltransferases and Demethylases n Targeting the Ubiquitin Proteasome System n Targeting the Unfolded Protein Response n Targeting the Microbiome n Kinase Inhibitor Discovery n GPCR-Based Drug Discovery - Part 1 n GPCR-Based Drug Discovery - Part 2 n Antibodies Against Membrane Protein Targets - Part 1 n Antibodies Against Membrane Protein Targets - Part 2 n RNAi for Functional Genomics Screening n New Frontiers in Gene Editing n Gene Therapy Breakthroughs n Quantitative Systems Pharmacology n Targeting Ocular Disorders SYMPOSIA Plenary Session Speakers SEPTEMBER 21 PLENARY KEYNOTE INTRODUCTION: Comprehensive Sponsored by n Next-Generation Histone Deacetylase Inhibitors Kinase and Epigenetic Compound Profiling n Strategies for Rare Diseases Kelvin Lam, Ph.D. SEPTEMBER 22 Director, Strategic Partnerships, Reaction Biology Corporation n Developing CRISPR-Based Therapies iPS Cell Technology, Gene Editing and Disease Research EVENT FEATURES Rudolf Jaenisch, M.D. Founding Member, Whitehead Institute for Biomedical Research; n 15 Conferences n 15 Short Courses Professor, Department of Biology, Massachusetts Institute of Technology n 3 Symposia n 65 Exhibitors n 130+ Posters n Plenary Keynote Speakers The Evolutionary Dynamics and Treatment of Cancer Martin Nowak, Ph.D., M.Sc. n 40+ Interactive Breakout Discussion Groups Professor, Biology and Mathematics and Director, Program for Evolutionary Dynamics, Harvard University DiscoveryOnTarget.com PREMIER SPONSORS CONFERENCE-AT-A-GLANCE *Separate registration required for Short Courses and Symposia Monday Tuesday - Wednesday a.m.
    [Show full text]