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Twists and Turns in Protein Assembly
Twists and Turns in Protein Assembly Professor Robert Fairman TWISTS AND TURNS IN PROTEIN ASSEMBLY In nerve cells, the accumulation of protein into bundles of insoluble fibres is the underlying cause of a number of neurodegenerative diseases. Professor Robert Fairman and his team at Haverford College are developing cutting edge techniques to unravel this process. Proteins are the building blocks of life. The leads to the death of particularly vulnerable genetic code within each cell of our bodies cells such as neurones – the elaborate and controls the sequence of molecules called sensitive cells in our brain. This is the basic amino acids, which assemble together mechanism that causes the debilitating and to form each protein. But this is only the currently untreatable neurological disorder first step. Amino acids are small charged Huntington’s disease, which is characterised molecules that interact with one another as by a disruption of normal movements and they join together to form strings of peptides a decline in mental ability, resulting in (polypeptides), which spontaneously develop dementia. into different structures known as secondary structures. This can involve the formation ‘The relationship of this aggregation to of sheets or helical spirals following certain disease is poorly understood, and differences rules determined by the order of the amino in protein structure may underlie differences acids. These secondary structures then in toxicity,’ Professor Fairman admits. ‘Many interact with one another to form larger neurodegenerative diseases (Alzheimer’s, tertiary structures of proteins that control Huntington’s, Parkinson’s) have a similar and mediate every aspect of cell function. underlying molecular mechanism of protein aggregation, involving the formation of ‘Ever since I was an undergraduate student, an extended polypeptide chain that can I’ve always been fascinated with a chemical aggregate through ß-sheet formation.’ view of biology,’ Professor Fairman tells As such, it is vital to understand how Scientia. -
CURRICULUM VITAE Laura Finzi
CURRICULUM VITAE Laura Finzi Physics Department, Emory University e-mail: [email protected] 400 Dowman Dr, Atlanta, GA 30322 http://www.physics.emory.edu/faculty/finzi/ tel. 404-727-4930 ; fax: 404-727-0873 EDUCATION_________________________________________________________________________________ 1990 Ph.D. in Chemistry, University of New Mexico, Albuquerque, NM. (Advisor: Carlos Bustamante) 1987 Master's in Chemistry, University of New Mexico, Albuquerque, NM. 1984 Laurea in Industrial Chemistry, University of Bologna, Bologna, Italy. 1979 Diploma from Liceo Classico "M. Minghetti" (High School diploma), Bologna, Italy. PROFESSIONAL ACTIVITY____________________________________________________________________ September 2012 - present: Full Professor, Physics Department, Emory University. July 2005-August 2012: Associate Professor, Physics Department, Emory University. June 1999-June 2005: Tenured Researcher and Group Leader, Biology Dept, University of Milano, Italy. 1993-May 1999: Researcher (tenured in ’96), Biology Dept, University of Milan, Italy. 1992-1993: Post Doctoral Fellow, Biochemistry Dept., Brandeis University (Mentor: Jeff Gelles). 1990-1991: Post Doctoral Fellow, Chem. Dept., University of New Mexico (October-December 1990), Institute of Molecular Biology, University of Oregon (January-December 1991) (Carlos Bustamante group). HONORS and AWARDS________________________________________________________________________ 2018: Recognized for “Excellent Teaching” by Phi Beta Kappa Mentee. Ceremony held on 4/10 in Cannon Chapel. -
'Epigenetic Landscape' Is Protective in Normal Aging, Impaired in Alzheimer's Disease 5 March 2018
'Epigenetic landscape' is protective in normal aging, impaired in Alzheimer's disease 5 March 2018 compaction of chromosomes in the nucleus (called acetylation of lysine 16 on histone H4, or H4K16ac for short). Changes to the way H4K16ac is modified along the genome in disease versus normal aging brains may signify places for future drug development. Because changes in H4K16ac govern how genes are expressed, the location and amount of epigenetic alterations is called the "epigenetic landscape." "This is the first time that we have been able to look at these relationships in human tissue by using donated postmortem brain tissue from the Penn Brain Bank," said Shelley Berger, PhD, a professor of Cell and Developmental Biology in the Perelman School of Medicine and a professor of Biology in the School of Arts and Sciences. "Our results Coronal section of human brain indicating the lateral establish the basis for an epigenetic link between temporal lobe (red circle) used in this study. Credit: aging and Alzheimer's disease." Coronal section of human brain indicating The lab of Shelley Berger, PhD, Perelman School of Medicine, Berger, also the director of the Penn Epigenetics University of Pennsylvania Institute, Nancy Bonini, PhD, a professor of Biology, and Brad Johnson, MD, PhD, an associate professor of Pathology and Laboratory Medicine, are co-senior authors of the new study. Although certain genetic variants increase the risk of Alzheimer's disease (AD), age is the strongest H4K16ac is a key modification in human health known risk factor. But the way in which molecular because it regulates cellular responses to stress processes of aging predispose people to AD, or and to DNA damage. -
St. Geme Symposium Pediatrics, University of Sponsored by the Colorado, AMC Section of Developmental Biology
Department of St. Geme Symposium Pediatrics, University of Sponsored by the Colorado, AMC Section of Developmental Biology September 10, 2020 2:00pm-4:00pm Speaking Schedule Introduction by Dr. Bruce Appel, Section Head, The St. Geme Symposium Developmental Biology will be held this year in association with the St. 2:00 Caleb Doll, PhD – Fragility in specification; roles for Geme Lectureship, an the RNA binding protein FMRP in gliogenesis annual event in honor of 2:15 Agnese Kocere – RBM8A deficiency in TAR syndrome Dr. Joseph St. Geme, a impacts the lateral plate mesoderm former Dean of the 2:30 Julia Derk, PhD – A critical role for Wnt suppression in School of Medicine. The the development of the arachnoid barrier of the purpose of the meninges Symposium is to 2:45 Kelly Sullivan, PhD – Normalization of Interferon introduce research Receptor Gene Dosage in Mouse Model of Down performed in the Section Syndrome of Developmental Biology 3:00 Yunus Ozekin – Exploring the Effects of Prenatal to our St. Geme Lecturer, ECigarette Exposure on Craniofacial Development Dr. Nancy Bonini, 3:15 Jessica Warns, PhD – Does NF‐Y regulate cilia gene members of the St. Geme networks? family and the Anschutz 3:30 Kayt Scott – Prdm8 regulates pMN progenitor Medical Campus specification for motor neuron and oligodendrocyte community. fates by modulating Shh signaling response 3:45 Peter Dempsey, PhD ‐ Cellular Plasticity of Intestinal Secretory Progenitors in Response to Injury Zoom link https://ucdenver.zoom.us/j/921 40407653 Developmental Biology faculty, post-doctoral fellows About the Section of and student’s biographical information: Developmental Biology: Dempsey, Peter, PhD - Associate Professor Dr. -
NCI Laboratory of Molecular Biology Oral History Project Interview #1 with Dr
NCI Laboratory of Molecular Biology Oral History Project Interview #1 with Dr. Sankar L. Adhya Conducted on October 1, 2008, by Jason Gart JG: My name is Jason Gart and I am a senior historian and History Associates Incorporated in Rockville, Maryland. Today’s date is October 1, 2008, and we are in the offices of the National Institutes of Health in Bethesda, Maryland. Please state your full name and also spell it. SA: Sankar Adhya. S-A-N-K-A-R—A-D-H-Y-A. JG: Terrific, thank you. The subject of this interview is the Laboratory of Molecular Biology. Established in 1970, the Laboratory of Molecular Biology (LMB), Center for Cancer Research, National Cancer Institute, National Institutes of Health, currently has among its ten groups four members of the National Academy of Sciences. LMB has trained many other prominent scientists and its researchers have contributed both to basic science and to novel applied cancer treatments. LMB has initiated this oral history project to capture recollections of prominent scientists currently and formerly associated with the laboratory. To begin please talk about where you were born and your interests as a child. Explain your family background and what your parents did for a living? Interview #1 with Dr. Sankar L. Adhya, October 1, 2008 2 SA: I was born in Kolkata (Calcutta), India, in a large family where my father lived with many other members of his family, like his brothers and so on. My father was a lawyer, my mother was a housewife. I grew up in a family mostly involved in law or real estate business and no scientists. -
Temporal Patterns of Short Non-Coding Rna Modifications And
TEMPORAL PATTERNS OF SHORT NON-CODING RNA MODIFICATIONS AND EXPRESSION by AMMAR S. NAQVI A dissertation submitted to the Graduate School – Camden Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Doctor of Philosophy Graduate Program in Computational and Integrative Biology Written under the direction of Dr. Andrey Grigoriev And approved by ________________________ Andrey Grigoriev ________________________ Jongmin Nam ________________________ Nancy Bonini Camden, New Jersey May 2015 ABSTRACT OF THE DISSERTATION Temporal Patterns of non-coding RNA Modifications and Expression by AMMAR S. NAQVI Dissertation Director: Dr. Andrey Grigoriev We investigated the function and properties of small RNAs, particularly microRNAs and tRNA-derived fragments (tRFs) with age. We report the characterization of a novel 3'-to- 5' exonuclease, Nibbler (Nbr), that generates differing isoforms of miRNAs in Drosophila. We developed a robust approach to help identify and characterize 3' heterogeneity in microRNAs controlled by Nbr, which assisted in identifying age- associated traits, including neurodegeneration and lifespan. Subsequently, given the fact Nbr interacts with Ago1 and not Ago2, we observed an accumulation of certain isoforms, which lead us to ask if there were particular patterns and trends that were Ago-specific. Interestingly, we report a novel age-associated change of select isoforms with age that is Ago2 specific. RNA deep-sequencing analysis coupled with experimental evidence reflected an increased loading of miRNA isoforms into Ago2 with age. Essentially, the loss of methylated miRNAs led to accelerated brain degeneration and shortened lifespan. Intriguingly, we also observed and identified Ago-loaded tRFs, which appear to have properties similar to those of miRNAs. -
Cold Spring Harbor Symposia on Quantitative Biology
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLV---PART 1 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLV MOVABLE GENETIC ELEMENTS COLD SPRING HARBOR LABORATORY 1981 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLV 1981 by The Cold Spring Harbor Laboratory International Standard Book Number 0-87969-044-5 Library of Congress Catalog Card Number 34-8174 Printed in the United States of America All rights reserved COLD SPRING HARBOR SYMPOSIA ON QUANT1TA T1VE BIOLOGY Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936 Previous Symposia Volumes I (1933) Surface Phenomena XXIII (1958) Exchange of Genetic Material: Mechanism I1 (1934) Aspects of Growth and Consequences Ili (1935) Photochemical Reactions XX1V (1959) Genetics and Twentieth Century Darwinism IV (1936) Excitation Phenomena XXV (1960) Biological Clocks V (1937) Internal Secretions XXV1 (I 961) Cellular Regulatory Mechanisms VI (1938) Protein Chemistry XXVll (1962) Basic Mechanisms in Animal Virus Biology VII (1939) Biological Oxidations XXVIlI (1963) Synthesis and Structure of Macromolecules VIII (1940) Permeability and the Nature of Cell Mem- XXIX (1964) Human Genetics branes XXX (1965) Sensory Receptors 1X (1941) Genes and Chromosomes: Structure and Organi- XXXI (1966) The Genetic Code zation XXXII (1967) Antibodies X (1942) The Relation of Hormones to Development XXXIlI (1968) Replication of DNA in Microorganisms XI (1946) Heredity and Variation in Microorganisms. XXX1V (1969) The Mechanism of Protein -
TFEB/Mitf Links Impaired Nuclear Import to Autophagolysosomal
RESEARCH ARTICLE TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9- ALS Kathleen M Cunningham1, Kirstin Maulding1, Kai Ruan2, Mumine Senturk3, Jonathan C Grima4,5, Hyun Sung2, Zhongyuan Zuo6, Helen Song2, Junli Gao7, Sandeep Dubey2, Jeffrey D Rothstein1,2,4,5, Ke Zhang7, Hugo J Bellen3,6,8,9,10, Thomas E Lloyd1,2,5* 1Cellular and Molecular Medicine Program, School of Medicine, Johns Hopkins University, Baltimore, United States; 2Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, United States; 3Program in Developmental Biology, Baylor College of Medicine (BCM), Houston, United States; 4Brain Science Institute, School of Medicine, Johns Hopkins University, Baltimore, United States; 5Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, United States; 6Department of Molecular and Human Genetics, BCM, Houston, United States; 7Department of Neuroscience, Mayo Clinic, Jacksonville, United States; 8Department of Neuroscience, BCM, Houston, United States; 9Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; 10Howard Hughes Medical Institute, Houston, United States Abstract Disrupted nucleocytoplasmic transport (NCT) has been implicated in neurodegenerative disease pathogenesis; however, the mechanisms by which disrupted NCT causes neurodegeneration remain unclear. In a Drosophila screen, we identified ref(2)P/p62, a key regulator of autophagy, as a potent suppressor of neurodegeneration caused by the GGGGCC hexanucleotide repeat expansion (G4C2 HRE) in C9orf72 that causes amyotrophic lateral sclerosis *For correspondence: [email protected] (ALS) and frontotemporal dementia (FTD). We found that p62 is increased and forms ubiquitinated aggregates due to decreased autophagic cargo degradation. Immunofluorescence and electron Competing interest: See microscopy of Drosophila tissues demonstrate an accumulation of lysosome-like organelles that page 18 precedes neurodegeneration. -
Polyq Expansions in Ataxin-2—A Risk Factor for Amyotrophic Lateral Sclerosis?
RESEARCH HIGHLIGHTS MOTOR NEURON DISEASE PolyQ expansions in ataxin-2—a risk factor for amyotrophic lateral sclerosis? ntermediate-length polyglutamine (polyQ) expansions in the ataxin-2 I(ATXN2) gene could confer an increased risk of developing amyotrophic lateral sclerosis (ALS), according to research from a team led by Aaron Gitler and Nancy Bonini at the University of Pennsylvania, USA. Their findings indicate that ataxin-2 enhances the toxicity of TAR DNA-binding protein 43 (TDP-43)—a molecule that has already been strongly implicated in ALS pathogenesis—and the interaction between these two proteins could A combination of approaches involving yeast cells (left), Drosophila (center) and human motor neurons (right) has identified a provide a lead for the development of role for ataxin-2 in amyotrophic lateral sclerosis. Images provided by Professor Nancy Bonini and Professor Aaron Gitler. much-needed new therapies for ALS. Permission obtained from Nature Publishing Group © Elden, A. C. et al. Nature 466, 1069–1075 (2010). Long polyQ expansions (>34 glutamines) in the ATXN2 gene have overexpressed, increased TDP-43 toxicity. degradation, thereby increasing its previously been shown to cause the One of these genes was PBP1, the yeast concentration in the cell. hereditary neurodegenerative disease ortholog of ATXN2. These new findings identify ATXN2 spinocerebellar ataxia type 2 (SCA2). To examine the effects of the ATXN2– as a susceptibility gene for ALS, as well Gitler, Bonini and colleagues measured TDP-43 interaction in the context of as providing a number of avenues for ATXN2 polyQ repeat lengths in 915 the nervous system, the researchers further investigation of the underlying patients with sporadic or familial ALS, switched their attention to a Drosophila disease mechanisms. -
NEWSLETTER VOLUME 35, NUMBER 6 Student/Postdoc- Led Local Meetings NIH Working Group Proposes Page 3 Training Changes More ASCB Award the Recommendations of a U.S
ASCB J U L Y 2 0 1 2 NEWSLETTER VOLUME 35, NUMBER 6 Student/Postdoc- Led Local Meetings NIH Working Group Proposes Page 3 Training Changes More ASCB Award The recommendations of a U.S. National Institutes of Health (NIH) Working Group on the Announcements biomedical research workforce include changes in the programs offered by academic institutions, Page 8 limits on NIH support for graduate students, and changes in the way graduate students and postdocs are supported. The Working Group, a subcommittee of the Advisory Committee to An Innovative the NIH Director, was formed in January 2011 by NIH Director Francis Collins to examine Approach to Dual- the state of the biomedical research workforce and make recommendations to ensure the future Career Support competitiveness of the U.S. biomedical research enterprise. Page 11 The Biomedical Research Workforce Working Group was co-chaired by Shirley Tilghman and Sally Rockey, NIH Deputy Director for Extramural Research, and included ASCB members Leemor Joshua-Tor and Keith Yamamoto. In June 2012, the Working Group sent its report, with a series of recommendations, to Collins for his review and consideration. Inside Despite low unemployment for biomedical PhDs, the percentage of PhDs who move into President’s Column 3 tenured or tenure-track positions has declined by 8% since 1993. In contrast, science-related Did You Know? 6 occupations that do not involve the conduct of research or do not require graduate training WICB Junior, Senior Awards 8 are seeing increases in employment. According to -
CV Yuanquan 3-23-16
Yuanquan Song Ph.D. [email protected] Yuanquan Song Ph.D. Department of Physiology University of California San Francisco and HHMI 1550 4th Street RM RH481 San Francisco, CA 94158 (267) 679-9833 [email protected] Positions 05/2016 – Assistant Professor of Pathology and Laboratory Medicine Center for Cellular and Molecular Therapeutics (CCMT) at the Children's Hospital of Philadelphia (CHOP), University of Pennsylvania 09/2009 – 04/2016 Postdoctoral Fellow Dept. of Physiology, Univ. of California San Francisco and HHMI Mentor: Dr. Yuh Nung Jan, Ph.D. Education 05/2015 Spinal Cord Injury Training Program (SCITP) Dept. of Neuroscience, Ohio State University, Columbus, OH 2003 – 2009 Ph.D. in Neuroscience Univ. of Pennsylvania School of Medicine, Philadelphia, PA 1998 – 2002 B.S. in Biotechnology Shanghai Jiao Tong University, Shanghai, China Research Experience 09/2009 – present UCSF Yuh Nung Jan Lab Postdoctoral Fellow Research Projects: Cellular and molecular mechanisms underlying axon and dendrite degeneration and regeneration Neural and molecular substrates for the plasticity of aggression 02/2004 – 08/2009 UPenn Rita Balice-Gordon Lab Graduate Student Research Projects: Cellular and molecular mechanisms underlying neural circuitry formation and function Zebrafish model of MLL leukemogenesis Zebrafish model of neurodegenerative diseases 09/2003 – 12/2003 UPenn Irwin Levitan Lab Pre-dissertation Laboratory Rotation Research Project: Regulation of sodium-potassium ATPase by its binding protein mSlob 06/2003 – 08/2003 UPenn Nancy Bonini Lab Pre-dissertation Laboratory Rotation Research Project: Molecular mechanisms of polyglutamine diseases 07/2002 – 05/2003 Institute of Neuroscience, Academy of Sciences, Shanghai, China Research Assistant in the Lab of Shu-Min Duan, Xiao-Bing Yuan, and Mu-Ming Poo Research Project: Axon guidance and Rho GTPase signaling Awards and Fellowships 1 Yuanquan Song Ph.D. -
Biological Consequences of Tightly Bent DNA: the Other Life of a Macromolecular Celebrity
University of Pennsylvania ScholarlyCommons Department of Physics Papers Department of Physics 10-2006 Biological Consequences of Tightly Bent DNA: The Other Life of a Macromolecular Celebrity Hernan G. Garcia Paul Grayson Lin Han Mandar Inamdar Jané Kondev See next page for additional authors Follow this and additional works at: https://repository.upenn.edu/physics_papers Part of the Physics Commons Recommended Citation Garcia, H. G., Grayson, P., Han, L., Inamdar, M., Kondev, J., Nelson, P. C., Phillips, R., Widom, J., & Wiggins, P. A. (2006). Biological Consequences of Tightly Bent DNA: The Other Life of a Macromolecular Celebrity. Biopolymers, 85 115-130. http://dx.doi.org/10.1002/bip.20627 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/physics_papers/503 For more information, please contact [email protected]. Biological Consequences of Tightly Bent DNA: The Other Life of a Macromolecular Celebrity Abstract The mechanical properties of DNA play a critical role in many biological functions. For example, DNA packing in viruses involves confining the viral genome in a volume (the viral capsid) with dimensions that are comparable to the DNA persistence length. Similarly, eukaryotic DNA is packed in DNA-protein complexes (nucleosomes) in which DNA is tightly bent around protein spools. DNA is also tightly bent by many proteins that regulate transcription, resulting in a variation in gene expression that is amenable to quantitative analysis. In these cases, DNA loops are formed with lengths that are comparable to or smaller than the DNA persistence length. The aim of this review is to describe the physical forces associated with tightly bent DNA in all of these settings and to explore the biological consequences of such bending, as increasingly accessible by single-molecule techniques.