DOCSLIB.ORG

Sackler Faculty of Medicine Preclinical Research 2020 Sections

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sackler Faculty of Medicine Preclinical Research 2020 Sections Sackler Faculty of Medicine Preclinical Research 2020 Sections Cancer and Molecular Therapies 8 Cardiovascular Research and Diseases 44 Dental Health and Medicine 56 Diabetes, Metabolic and Endocrine Diseases 65 Genomics & Personalized Medicine 78 Hearing, Language & Speech Sciences and Disorders 99 Infectious Diseases 120 Inflammatory and Autoimmune Diseases 139 Medical Education and Ethics 150 Nervous System and Brain Disorders 158 Nursing, Occupational and Physical Therapy 208 Public Health 248 Reproduction, Development and Evolution 277 Stem Cells, Regenerative Medicine and Aging 298 Cover images (from bottom left, clockwise): Image 1: Human embryonic stem cell derived cardiomyocytes stained with fluorescent antibodies. The cardiac marker alpha-actinin (green), calcium channel modulator, Ahnak1 (red) – Shimrit Oz, Nathan Dascal. Image 2: Islet of Langerhans containing insulin-producing beta-cells (green) and glucagon- producing alpha-cells (red) – Daria Baer, Limor Landsman. Image 3: β-catenin in C. elegans vulva – Michal Caspi, Limor Broday, Rina Rosin-Arbesfeld. Image 4: Stereocilia of a sensory outer hair cell from a mouse inner ear – Shaked Shivatzki, Karen Avraham. Image 5: Electron scanning micrograph of middle ear ossicles from a mouse ear stained with pseudo colors – Shaked Shivatski, Karen Avraham. Image 6: Resistin-like molecule alpha (red), eosinophil major basic protein (green) and DAPI (blue) staining of asthmatic mice – Danielle Karo-Atar, Ariel Munitz. © All rights reserved Editor: Prof. Karen Avraham Graphic design: Michal Semo Kovetz, TAU Graphic Design Studio October 2020 Sackler Faculty of Medicine Research 2020 2 The Sackler Faculty of Medicine The Sackler Faculty of Medicine is Israel’s largest diabetes, neurodegenerative diseases, infectious medical research and training complex. The Sackler diseases and genetic diseases, including but not Faculty of Medicine of Tel Aviv University (TAU) was imited to Alzheimer’s disease, Parkinson’s disease founded in 1964 following the generous contributions and HIV/AIDS. Physicians in 181 Sacker affiliated of renowned U.S. doctors and philanthropists departments and institutes in 17 hospitals hold Raymond, and the late Mortimer and Arthur Sackler. academic appointments at TAU. The Gitter-Smolarz Research at the Sackler Faculty of Medicine is Life Sciences and Medicine Library serves students multidisciplinary, as scientists and clinicians combine and staff and is the center of a consortium of 15 efforts in basic and translational research. Research hospital libraries. is conducted in the laboratories on the TAU campus, The student body is made up of 750 Israeli students and in the clinical facilities affiliated to the Faculty. enrolled in the 6-year M.D. degree program, 300 The Faculty of Medicine includes the Sackler School American and Canadian students enrolled in a of Medicine, the School of Health Professions, the 4-year M.D. program chartered by the State of School of Public Health, and the School of Dental New York and accredited by the State of Israel, Medicine. Education takes place in all these schools and a 4-year program for Israeli students for the and in the Graduate School of Medicine, School of Continuing Medical Education, the New York M.D. degree, with 260 students. Approximately State American Program and the B.Sc. Program in 200 students study dental medicine in a six-year Medical Life Sciences. This network of preclinical program where they are awarded the D.M.D. degree and clinical teams helps realize the ultimate goals and another 2,000 students are enrolled in the of the research: the basic understanding of human health professions programs where they will earn pathophysiology and the prevention, diagnosis and degrees in Communications Disorders, Nursing, treatment of disease. The research of Preclinical Physical Therapy and Occupational Therapy. faculty members from the Sackler School of Medicine Sackler’s Graduate School for Advanced Studies are featured in this research brochure. trains approximately 800 masters and doctoral level students in the biomedical disciplines, with a The Faculty of Medicine engages in joint teaching special emphasis on a multidisciplinary approach and and research programs with nearly every faculty at application of fundamental knowledge to important TAU, including the Wise Faculty of Life Sciences, biomedical problems. the Sagol School of Neuroscience, the Edmond J. Safra Bioinformatics Center, the TAU Center for The Sackler Faculty of Medicine is led by the Dean, Nanoscience and Nanotechnology, and the Edmond Professor Ehud Grossman; Vice Deans Prof. Karen J. Safra Center for Ethics, and multi-nationally with Avraham, Prof. Iris Barshack, Prof. Moshe Phillip, schools, hospitals and research centers throughout Prof. Anat Lowenstein, Prof. Ami Fishman, Prof. the world. The Sackler faculty is known for research Arnon Wiznitzer and Assistant to the Dean, Ms. in the following areas: cancer biology, stem cells, Michal Gilboa. Sackler Faculty of Medicine Research 2020 3 The Sackler Faculty of Medicine Table of Contents Cancer and Molecular Therapies 8 Dr. Uri Ben-David 9 Dr. Yaron Carmi, Ph.D. 12 Dr. Merav Cohen, Ph.D. 14 Prof. Neta Erez, Ph.D. 16 Prof. Zvi Fishelson, Ph.D. 19 Prof. Tamar Geiger, Ph.D. 21 Prof. Shai Izraeli, M.D 25 Prof. Yona Keisari, Ph.D. 29 Prof. Rafi Korenstein, Ph.D. 31 Prof. Rina Rosin-Arbesfeld, Ph.D. 33 Prof. Ronit Satchi-Fainaro, Ph.D. 35 Prof. Yosef Shiloh, Ph.D. 40 Prof. Ilan Tsarfaty, Ph.D. 42 Cardiovascular Research and Diseases 44 Prof. Bernard Attali, Ph.D. 45 Prof. Nathan Dascal, Ph.D. 47 Dr. Michal Katz-Leurer, Ph.D. 49 Prof. Daniel Khananshvili, Ph.D. 51 Prof. Jonathan Leor, M.D. 53 Dental Health and Medicine 56 Dr. Lihi Adler-Abramovich, Ph.D. 57 Prof. Tamar Brosh, Ph.D. 60 Prof. Ilana Eli, D.M.D. 62 Dr. Rachel Sarig, Ph.D., D.M.D. 63 Diabetes, Metabolic and Endocrine Diseases 65 Prof. Shimon Efrat, Ph.D. 66 Prof. Koret Hirschberg, Ph.D. 67 Dr. Limor Landsman, Ph.D. 69 Prof. Drorit Neumann, Ph.D. 71 Prof. Haim Werner, Ph.D. 73 Prof. Efrat Wertheimer, MD., PhD. 76 Genomics & Personalized Medicine 78 Prof. Gil Ast, Ph.D. 79 Prof. Karen B. Avraham, Ph.D. 81 Dr. Ran Elkon, Ph.D. 84 Prof. David Gurwitz, Ph.D. 86 Sackler Faculty of Medicine Research 2020 4 Table of Contents Prof. Carmit Levy, Ph.D. 89 Prof. Zvi (Gregory) Livshits, Ph.D. 91 Prof. Noam Shomron, Ph.D. 94 Hearing, Language & Speech Sciences and Disorders 99 Dr. Noam Amir, D.Sc. 100 Prof. Ofer Amir, Ph.D. 102 Dr. Daphne Ari-Even Roth, Ph.D. 104 Dr. Katy Borodkin, Ph.D. 106 Prof. Yael Henkin, Ph.D. 108 Prof. Minka Hildesheimer, Ph.D. 110 Prof. Liat Kishon-Rabin, Ph.D. 112 Prof. Tova Most, Ph.D. 115 Prof. Chava Muchnik, Ph.D. 117 Prof. Dorit Ravid, Ph.D. 118 Dr. Yael Zaltz, Ph.D. 119 Infectious Diseases 120 Prof. Elhanan Borenstein, Ph.D. 121 Dr. Natalia T. Freund, Ph.D. 124 Prof. Fuad Iraqi, Ph.D. 126 Dr. Oren Kobiler, M.D., Ph.D. 128 Prof. Nir Osherov, Ph.D. 129 Prof. Udi Qimron, Ph.D. 131 Dr. Dor Salomon, Ph.D. 133 Prof. Esther Segal, Ph.D. 135 Dr. Ella Sklan, Ph.D. 137 Inflammatory and Autoimmune Diseases 139 Dr. Maayan Gal, Ph.D. 140 Dr. Asaf Madi, Ph.D. 142 Prof. Ariel Munitz, Ph.D. 144 Prof. Mordechay (Motti) Gerlic, Ph.D. 146 Prof. Ronit Sagi-Eisenberg, Ph.D. 148 Medical Education and Ethics 150 Dr. Oren Asman, LL.D., Adv. 151 Prof. Yechiel Michael Barilan, M.D., M.A. 152 Dr. Ilana Dubovi, Ph.D. 154 Prof. Orit Karnieli-Miller, Ph.D. 156 Sackler Faculty of Medicine Research 2020 5 Hearing, Language & Speech Sciences and Disorders 99 Nervous System and Brain Disorders 158 Prof. Ruth Ashery-Padan, Ph.D. 159 Dr. Avraham Ashkenazi, Ph.D. 161 Prof. Hagit Eldar-Finkelman, Ph.D. 163 Dr. Jason Friedman, Ph.D. 164 Prof. Illana Gozes, Ph.D. 166 Dr. Yoni Haitin, Ph.D. 171 Prof. Talma Hendler, M.D., Ph.D. 173 Dr. Tal Laviv, Ph.D. 177 Prof. Dario G. Liebermann, Ph.D. 179 Prof. Ilana Lotan, Ph.D. 181 Prof. Yuval Nir, Ph.D. 183 Prof. Daniel Offen, Ph.D. 185 Dr. Moshe Parnas, Ph.D. 188 Prof. Eran Perlson, Ph.D. 190 Prof. Chaim G. (Chagi) Pick, Ph.D. 193 Prof. Moshe Rehavi, Ph.D. 196 Dr. Moran Rubinstein, Ph.D. 197 Prof. Naphtali Savion, Ph.D. 199 Prof. Inna Slutsky, Ph.D. 200 Prof. Arieh S. Solomon, M.D., Ph.D. 202 Dr. Eran Stark, M.D., Ph.D. 204 Dr. Ido Tavor, Ph.D. 206 Nursing, Occupational and Physical Therapy 208 Dr. Michal Avrech Bar, Ph.D., O.T. 209 Dr. Tami Bar-Shalita, Ph.D., O.T. 211 Prof. Sivia Barnoy, R.N., Ph.D. 213 Dr. Orit Bart, Ph.D., OTR 215 Prof. Ruth Defrin, Ph.D. 217 Dr. Michal Itzhaki, R.N., Ph.D. 220 Dr. Ilya Kagan, R.N., Ph.D. 222 Prof. Silvia Koton, Ph.D., M.Occ.H., R.N. 224 Dr. Yael Lahav, Ph.D. 226 Dr. Lena Lipskaya-Velikovsky, Ph.D., O.T. 228 Dr. Alon Kalron, Ph.D., P.T. 229 Dr. Youssef Masharawi, Ph.D., B.P.T. 233 Dr. Semyon Melnikov, R.N. Ph.D. 235 Dr. Sigal Portnoy, Ph.D. 237 Dr. Debbie Rand, Ph.D., O.T. 240 Sackler Faculty of Medicine Research 2020 6 Nervous System and Brain Disorders 158 Prof. Navah Z. Ratzon, Ph.D., O.T. 242 Dr. Angela Ruban, Ph.D. 244 Dr. Miriam Theilla, Ph.D. 246 Public Health 248 Dr. Bruria Adini, Ph.D. 249 Prof. Daniel I. Cohen, Ph.D. 251 Prof. Jiska Cohen-Mansfield, Ph.D. 253 Dr. Yftach Gepner, Ph.D. 256 Prof. Yariv Gerber, Ph.D. 259 Prof. Uri Goldbourt, Ph.D. 261 Dr.
Load more

Recommended publications
  • Preclinical Research 2020 Sections
    Sackler Faculty of Medicine Preclinical Research 2020 Sections Cancer and Molecular Therapies 8 Dental Health and Medicine 52 Diabetes, Metabolic and Endocrine Diseases 62 Genomics & Personalized Medicine 78 Hearing, Language & Speech Sciences and Disorders 98 Infectious Diseases 117 Inflammatory and Autoimmune Diseases 137 Medical Education and Ethics 147 Nervous System and Brain Disorders 154 Nursing, Occupational and Physical Therapy 200 Public Health 235 Reproduction, Development and Evolution 263 Stem Cells and Regenerative Medicine 280 Cover images (from bottom left, clockwise): Image 1: Human embryonic stem cell derived cardiomyocytes stained with fluorescent antibodies. The cardiac marker alpha-actinin (green), calcium channel modulator, Ahnak1 (red) – Shimrit Oz, Nathan Dascal. Image 2: Islet of Langerhans containing insulin-producing beta-cells (green) and glucagon- producing alpha-cells (red) – Daria Baer, Limor Landsman. Image 3: β-catenin in C. elegans vulva – Michal Caspi, Limor Broday, Rina Rosin-Arbesfeld. Image 4: Stereocilia of a sensory outer hair cell from a mouse inner ear – Shaked Shivatzki, Karen Avraham. Image 5: Electron scanning micrograph of middle ear ossicles from a mouse ear stained with pseudo colors – Shaked Shivatski, Karen Avraham. Image 6: Resistin-like molecule alpha (red), eosinophil major basic protein (green) and DAPI (blue) staining of asthmatic mice – Danielle Karo-Atar, Ariel Munitz. © All rights reserved Editor: Prof. Karen Avraham Graphic design: Michal Semo Kovetz, TAU Graphic Design Studio February 2020 Sackler Faculty of Medicine Research 2020 2 The Sackler Faculty of Medicine The Sackler Faculty of Medicine is Israel’s largest diabetes, neurodegenerative diseases, infectious medical research and training complex. The Sackler diseases and genetic diseases, including but not Faculty of Medicine of Tel Aviv University (TAU) was imited to Alzheimer’s disease, Parkinson’s disease founded in 1964 following the generous contributions and HIV/AIDS.
    [Show full text]
  • Deep Multiomics Profiling of Brain Tumors Identifies Signaling Networks
    ARTICLE https://doi.org/10.1038/s41467-019-11661-4 OPEN Deep multiomics profiling of brain tumors identifies signaling networks downstream of cancer driver genes Hong Wang 1,2,3, Alexander K. Diaz3,4, Timothy I. Shaw2,5, Yuxin Li1,2,4, Mingming Niu1,4, Ji-Hoon Cho2, Barbara S. Paugh4, Yang Zhang6, Jeffrey Sifford1,4, Bing Bai1,4,10, Zhiping Wu1,4, Haiyan Tan2, Suiping Zhou2, Laura D. Hover4, Heather S. Tillman 7, Abbas Shirinifard8, Suresh Thiagarajan9, Andras Sablauer 8, Vishwajeeth Pagala2, Anthony A. High2, Xusheng Wang 2, Chunliang Li 6, Suzanne J. Baker4 & Junmin Peng 1,2,4 1234567890():,; High throughput omics approaches provide an unprecedented opportunity for dissecting molecular mechanisms in cancer biology. Here we present deep profiling of whole proteome, phosphoproteome and transcriptome in two high-grade glioma (HGG) mouse models driven by mutated RTK oncogenes, PDGFRA and NTRK1, analyzing 13,860 proteins and 30,431 phosphosites by mass spectrometry. Systems biology approaches identify numerous master regulators, including 41 kinases and 23 transcription factors. Pathway activity computation and mouse survival indicate the NTRK1 mutation induces a higher activation of AKT down- stream targets including MYC and JUN, drives a positive feedback loop to up-regulate multiple other RTKs, and confers higher oncogenic potency than the PDGFRA mutation. A mini-gRNA library CRISPR-Cas9 validation screening shows 56% of tested master regulators are important for the viability of NTRK-driven HGG cells, including TFs (Myc and Jun) and metabolic kinases (AMPKa1 and AMPKa2), confirming the validity of the multiomics inte- grative approaches, and providing novel tumor vulnerabilities.
    [Show full text]
  • Population Genomics in a Disease Targeted Primary Cell Model
    Downloaded from genome.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Population genomics in a disease targeted primary cell model Elin Grundberg,1,2,12 Tony Kwan,1,2,12 Bing Ge,2 Kevin C.L. Lam,2 Vonda Koka,2 Andreas Kindmark,3 Hans Mallmin,4 Joana Dias,2 Dominique J. Verlaan,1,2,5 Manon Ouimet,5 Daniel Sinnett,5,6 Fernando Rivadeneira,7,8 Karol Estrada,7 Albert Hofman,8 Joyce M. van Meurs,7 Andre´ Uitterlinden,7,8 Patrick Beaulieu,5 Alexandru Graziani,5 Eef Harmsen,2 O¨ sten Ljunggren,3 Claes Ohlsson,9 Dan Mellstro¨m,9 Magnus K. Karlsson,10 Olle Nilsson,4 and Tomi Pastinen1,2,11,13 1Department of Human Genetics, McGill University, Montre´al H3A 1B1, Canada; 2McGill University and Genome Que´bec Innovation Centre, Montre´al H3A 1A4, Canada; 3Department of Medical Sciences, Uppsala University, Uppsala 75185, Sweden; 4Department of Surgical Sciences, Uppsala University, Uppsala 75185, Sweden; 5Sainte-Justine University Health Center, Montre´al H3T 1C5, Canada; 6Department of Pediatrics, University of Montre´al, Montre´al H3T 1C5, Canada; 7Department of Internal Medicine, Erasmus MC, Rotterdam 3015GE, The Netherlands; 8Department of Epidemiology, Erasmus MC, Rotterdam 3015GE, The Netherlands; 9Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine, Go¨teborg University, Gothenburg 41345, Sweden; 10Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Science, Lund University and Department of Orthopaedics, Malmo¨University Hospital, Malmo¨20502, Sweden; 11Department of Medical Genetics, McGill University, Montre´al H3H 1P3, Canada The common genetic variants associated with complex traits typically lie in noncoding DNA and may alter gene regu- lation in a cell type-specific manner.
    [Show full text]
  • Supplementary Tables S1-S3
    Supplementary Table S1: Real time RT-PCR primers COX-2 Forward 5’- CCACTTCAAGGGAGTCTGGA -3’ Reverse 5’- AAGGGCCCTGGTGTAGTAGG -3’ Wnt5a Forward 5’- TGAATAACCCTGTTCAGATGTCA -3’ Reverse 5’- TGTACTGCATGTGGTCCTGA -3’ Spp1 Forward 5'- GACCCATCTCAGAAGCAGAA -3' Reverse 5'- TTCGTCAGATTCATCCGAGT -3' CUGBP2 Forward 5’- ATGCAACAGCTCAACACTGC -3’ Reverse 5’- CAGCGTTGCCAGATTCTGTA -3’ Supplementary Table S2: Genes synergistically regulated by oncogenic Ras and TGF-β AU-rich probe_id Gene Name Gene Symbol element Fold change RasV12 + TGF-β RasV12 TGF-β 1368519_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 42.22 5.53 75.28 1373000_at sushi-repeat-containing protein, X-linked 2 (predicted) Srpx2 19.24 25.59 73.63 1383486_at Transcribed locus --- ARE 5.93 27.94 52.85 1367581_a_at secreted phosphoprotein 1 Spp1 2.46 19.28 49.76 1368359_a_at VGF nerve growth factor inducible Vgf 3.11 4.61 48.10 1392618_at Transcribed locus --- ARE 3.48 24.30 45.76 1398302_at prolactin-like protein F Prlpf ARE 1.39 3.29 45.23 1392264_s_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 24.92 3.67 40.09 1391022_at laminin, beta 3 Lamb3 2.13 3.31 38.15 1384605_at Transcribed locus --- 2.94 14.57 37.91 1367973_at chemokine (C-C motif) ligand 2 Ccl2 ARE 5.47 17.28 37.90 1369249_at progressive ankylosis homolog (mouse) Ank ARE 3.12 8.33 33.58 1398479_at ryanodine receptor 3 Ryr3 ARE 1.42 9.28 29.65 1371194_at tumor necrosis factor alpha induced protein 6 Tnfaip6 ARE 2.95 7.90 29.24 1386344_at Progressive ankylosis homolog (mouse)
    [Show full text]
  • Loci Associated with Bone Strength in Laying Hens
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Epsilon Archive for Student Projects Faculty of Veterinary Medicine and Animal Science Department of Animal Breeding and Genetics Loci associated with bone strength in laying hens Biaty Raymond Examensarbete / Swedish University of Agricultural Sciences Master’s Thesis, 30 hp Department of Animal Breeding and Genetics 488 Uppsala 2016 Faculty of Veterinary Medicine and Animal Science Department of Animal Breeding and Genetics Loci associated with bone strength in laying hens Biaty Raymond Supervisors: D.J. De-Koning, SLU, Department of Animal Breeding and Genetics Anna Maria Johansson, SLU, Department of Animal Breeding and Genetics Examiner: Erling Strandberg, SLU, Department of Animal Breeding and Genetics Credits: 30 hp Course title: Degree project in Animal Science Course code: EX0556 Level: Advanced, A2E Place of publication: Uppsala Year of publication: 2016 Name of series: Examensarbete / Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics, 488 On-line publicering: http://epsilon.slu.se Key words: Osteoporosis, GWAS, Fracture, Genes, QTLs ABSTRACT One of the growing welfare concern in the layer industry is the high incidences of bone fracture. This is thought to result from reduction in bone strength due to osteoporosis which is exacerbated by environmental stresses and mineral deficiencies. Despite these factors however, the primary cause of bone weakness and the resulting fractures is believed to be genetic predisposition. In this study, we performed a genome-wide association study to identify with high reliability the loci associated with bone strength in laying hens. Genotype information and phenotype data were obtained from 752 laying hens belonging to the same pure line population.
    [Show full text]
  • Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain
    Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain By Lily Li Jin A thesis submitted in conformity with the requirements for the degree of Ph.D. in Molecular Genetics, Graduate Department of Molecular Genetics, in the University of Toronto © Copyright by Lily Li Jin (2015) Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho-Lyn SH2 Domain Lily Li Jin 2015 Ph.D. in Molecular Genetics Graduate Department of Molecular Genetics University of Toronto Abstract Protein-tyrosine phosphorylation (pY) is a minor but important protein post-translational modification that modulates a wide range of cellular functions and is involved in cancer. Dysregulation of tyrosine kinases (TKs) and protein-tyrosine phosphatases (PTPs) have been observed in multiple myeloma (MM) and acute myeloid leukemia (AML) and is a subject of study. Using recently developed mass spectrometry-based proteomics techniques, quantitative PTP expression and cellular pY profiles were generated for MM cell lines and mouse xenograft tumors, as well as primary AML samples. Integrated comprehensive analyses on these data implicated a subset of TKs and PTPs in MM and AML, with valuable insights gained on the dynamic regulation of pY in biological systems. In particular, I propose a model that describes the cellular pY state as a functional output of the total activated TKs and PTPs in the cell. My results show that the global pY profile in the cancer models is quantitatively related to the cellular levels of activated TKs and PTPs. Furthermore, the identity of the implicated TK/PTPs is system- ii dependent, demonstrating context-dependent regulation of pY.
    [Show full text]
  • Identification of Genetic Variation Using Next-Generation Sequencing
    Technische Universitat¨ Munchen¨ Lehrstuhl f¨urBioinformatik Identification of genetic variation using Next-Generation Sequencing Sebastian Hubert Eck Vollst¨andigerAbdruck der von der Fakult¨atWissenschaftszentrum Weihen- stephan f¨urErn¨ahrung,Landnutzung und Umwelt der Technischen Univer- sit¨atM¨unchen zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. H.-R. Fries Pr¨uferder Dissertation: 1. Univ.-Prof. Dr. H-W. Mewes 2. Univ.-Prof. Dr. R. Zimmer, Ludwig-Maximilians Universit¨atM¨unchen 3. Priv.-Doz. Dr. T. M. Strom Die Dissertation wurde am 30.07.2013 bei der Technischen Universit¨atM¨unchen eingereicht und am 27.01.2014 durch die Fakult¨atWissenschaftszentrum Wei- henstephan f¨urErn¨ahrung,Landnutzung und Umwelt angenommen. Summary The field of genetic research was drastically changed by the advent of next- generation DNA sequencing technologies during the last three years. These technologies are able to generate unparalleled amounts of DNA sequence in- formation at a cost that is several orders of magnitude lower than standard sequencing techniques. Employing this technology allows identification of dis- ease causative and disease associated mutations from a frequency spectrum previously not accessible with standard techniques. Even though showing great promise, researchers are also facing new challenges. In particular the handling and analysis of unprecedented amounts of data. The goal of this thesis was the conception and implementation of an auto- mated, computational analysis pipeline for next generation sequencing data in general and whole exome sequencing data in particular in order to robustly identify disease related mutations. The pipeline covers all key analysis steps including alignment to a reference genome, variant calling, quality filtering and annotation of identified variants, storage of all variants in a relational database and identification of putatively causative mutations.
    [Show full text]
  • NOM1 CRISPR/Cas9 KO Plasmid (M): Sc-436651
    SANTA CRUZ BIOTECHNOLOGY, INC. NOM1 CRISPR/Cas9 KO Plasmid (m): sc-436651 BACKGROUND APPLICATIONS The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and NOM1 CRISPR/Cas9 KO Plasmid (m) is recommended for the disruption of CRISPR-associated protein (Cas9) system is an adaptive immune response gene expression in mouse cells. defense mechanism used by archea and bacteria for the degradation of foreign genetic material (4,6). This mechanism can be repurposed for other 20 nt non-coding RNA sequence: guides Cas9 functions, including genomic engineering for mammalian systems, such as to a specific target location in the genomic DNA gene knockout (KO) (1,2,3,5). CRISPR/Cas9 KO Plasmid products enable the U6 promoter: drives gRNA scaffold: helps Cas9 identification and cleavage of specific genes by utilizing guide RNA (gRNA) expression of gRNA bind to target DNA sequences derived from the Genome-scale CRISPR Knock-Out (GeCKO) v2 library developed in the Zhang Laboratory at the Broad Institute (3,5). Termination signal Green Fluorescent Protein: to visually REFERENCES verify transfection CRISPR/Cas9 Knockout Plasmid CBh (chicken β-Actin 1. Cong, L., et al. 2013. Multiplex genome engineering using CRISPR/Cas hybrid) promoter: drives systems. Science 339: 819-823. 2A peptide: expression of Cas9 allows production of both Cas9 and GFP from the 2. Mali, P., et al. 2013. RNA-guided human genome engineering via Cas9. same CBh promoter Science 339: 823-826. Nuclear localization signal 3. Ran, F.A., et al. 2013. Genome engineering using the CRISPR-Cas9 system. Nuclear localization signal SpCas9 ribonuclease Nat. Protoc. 8: 2281-2308.
    [Show full text]
  • A 1.35 Mb DNA Fragment Is Inserted Into the DHMN1 Locus on Chromosome 7Q34–Q36.2
    Hum Genet (2016) 135:1269–1278 DOI 10.1007/s00439-016-1720-4 ORIGINAL INVESTIGATION A 1.35 Mb DNA fragment is inserted into the DHMN1 locus on chromosome 7q34–q36.2 Alexander P. Drew1 · Anthony N. Cutrupi1,3 · Megan H. Brewer1,3 · Garth A. Nicholson1,2,3 · Marina L. Kennerson1,2,3 Received: 5 April 2016 / Accepted: 25 July 2016 / Published online: 3 August 2016 © Springer-Verlag Berlin Heidelberg 2016 Abstract Distal hereditary motor neuropathies predomi- for hereditary motor neuropathies and highlights the grow- nantly affect the motor neurons of the peripheral nervous ing importance of interrogating the non-coding genome for system leading to chronic disability. Using whole genome SV mutations in families which have been excluded for sequencing (WGS) we have identified a novel structural genome wide coding mutations. variation (SV) within the distal hereditary motor neuropa- thy locus on chromosome 7q34–q36.2 (DHMN1). The SV involves the insertion of a 1.35 Mb DNA fragment Introduction into the DHMN1 disease locus. The source of the inserted sequence is 2.3 Mb distal to the disease locus at chromo- The distal hereditary motor neuropathies (dHMN) are a some 7q36.3. The insertion involves the duplication of five group of progressive neurodegenerative disorders that pri- genes (LOC389602, RNF32, LMBR1, NOM1, MNX1) and marily affect the motor neurons of distal limbs without partial duplication of UBE3C. The genomic structure of affecting sensory neurons. The disorder is a length depend- genes within the DHMN1 locus are not disrupted by the ant neuropathy in which the longest nerves are initially insertion and no disease causing point mutations within affected.
    [Show full text]
  • Mapping the Shh Long-Range Regulatory Domain Eve Anderson, Paul S
    © 2014. Published by The Company of Biologists Ltd | Development (2014) 141, 3934-3943 doi:10.1242/dev.108480 RESEARCH ARTICLE Mapping the Shh long-range regulatory domain Eve Anderson, Paul S. Devenney, Robert E. Hill* and Laura A. Lettice ABSTRACT spatiotemporal pattern of expression. With the coding region lying Coordinated gene expression controlled by long-distance enhancers is adjacent to a large gene desert, the expression is controlled by a cis orchestrated by DNA regulatory sequences involving transcription group of -regulators, many of which were identified by mouse factors and layers of control mechanisms. The Shh gene and well- transgenic reporter assays. Epstein et al. (1999) identified two ∼ established regulators are an example of genomic composition in intronic enhancers and one outside the gene, lying 9 kb upstream Shh Shh lacZ which enhancers reside in a large desert extending into neighbouring of . These potential enhancers of activate reporter genes to control the spatiotemporal pattern of expression. Exploiting expression within the ventral midline of the spinal cord and the local hopping activity of the Sleeping Beauty transposon, the hindbrain and the ventral midbrain and caudal region of the lacZ reporter gene was dispersed throughout the Shh region to diencephalon. A further study, using comparative sequence analysis systematically map the genomic features responsible for expression and mouse reporter assays, uncovered three forebrain enhancers Shh activity. We found that enhancer activities are retained inside a located 300-450 kb upstream of (Jeong et al., 2006). genomic region that corresponds to the topological associated domain Comparative genomics was also used to identify another more cis (TAD) defined by Hi-C.
    [Show full text]
  • Population Genomics in a Disease Targeted Primary Cell Model
    Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Population Genomics in a Disease Targeted Primary Cell Model Elin Grundberg1,2,12, Tony Kwan1,2,12, Bing Ge2, Kevin CL Lam2, Vonda Koka2, Andreas Kindmark3, Hans Mallmin4, Joana Dias2, Dominique J. Verlaan1,2,5, Manon Ouimet5, Daniel Sinnett5,6, Fernando Rivadeneira7,8, Karol Estrada7, Albert Hofman8, Joyce M van Meurs7, André Uitterlinden7,8, Patrick Beaulieu5, Alexandru Graziani5, Eef Harmsen2, Östen Ljunggren3, Claes Ohlsson9, Dan Mellström9, Magnus K Karlsson10, Olle Nilsson4 and Tomi Pastinen1,2,11 1Department of Human Genetics, McGill University, Montréal, Canada 2McGill University and Genome Québec Innovation Centre, Montréal, Canada 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden 4Department of Surgical Sciences, Uppsala University, Uppsala, Sweden 5Sainte‐Justine University Health Center, Montréal, Canada 6Department of Pediatrics, University of Montréal, Montréal, Canada 7Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands 8 Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands 9Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine, Göteborg University, Gothenburg, Sweden 10Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Science, Lund University and Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden 11Department of Medical Genetics, McGill University, Montréal, Canada 12These authors contributed equally
    [Show full text]
  • Prion Characterization Using Cell Based Approaches
    University of Kentucky UKnowledge Theses and Dissertations--Microbiology, Microbiology, Immunology, and Molecular Immunology, and Molecular Genetics Genetics 2012 PRION CHARACTERIZATION USING CELL BASED APPROACHES Vadim Khaychuk University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Khaychuk, Vadim, "PRION CHARACTERIZATION USING CELL BASED APPROACHES" (2012). Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics. 2. https://uknowledge.uky.edu/microbio_etds/2 This Doctoral Dissertation is brought to you for free and open access by the Microbiology, Immunology, and Molecular Genetics at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained and attached hereto needed written permission statements(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine). I hereby grant to The University of Kentucky and its agents the non-exclusive license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless a preapproved embargo applies.
    [Show full text]