Molecular Chaperones & Stress Responses
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[email protected] (609) 258-5981 Jonikaslab.Princeton.Edu Updated 3/10/2021
Martin Casimir Jonikas, Ph.D. Assistant Professor, Department of Molecular Biology Princeton University, Princeton, NJ 08544 [email protected] (609) 258-5981 jonikaslab.princeton.edu updated 3/10/2021 VISION My group seeks to advance the basic understanding of cell biology. We study the pyrenoid, a fascinating phase-separated organelle that enhances CO2 capture in nearly all eukaryotic algae. Understanding the pyrenoid is important for three reasons: (1) the pyrenoid plays a central role in our planet’s carbon cycle, (2) the pyrenoid embodies fundamental questions in organelle biogenesis, and (3) engineering a pyrenoid into land plants could dramatically increase crop yields. To accelerate progress, we are developing community resources for the unicellular green alga Chlamydomonas reinhardtii as a model system for photosynthetic organisms. My group also seeks to nurture and train future world-leading scientists. EDUCATION 2004 B.S., Aerospace Engineering, Massachusetts Institute of Technology 2009 Ph.D., Biochemistry and Molecular Biology, University of California, San Francisco. Research advisors: Dr. Jonathan Weissman and Dr. Peter Walter PROFESSIONAL POSITIONS 2010-2016 Young Investigator (faculty position equivalent to Assistant Professor), Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 2011-2016 Assistant Professor by courtesy, Department of Biology, Stanford University, Stanford, CA 2016-present Assistant Professor, Department of Molecular Biology, Princeton University, Princeton, NJ 2019-present Affiliated Faculty, Princeton Quantitative and Computational Biology Program AWARDS AND HONORS 2002 1st place, MIT 2.007 Robotics Competition 2005 National Science Foundation Graduate Research Fellowship 2009 Harvard Bauer Fellowship (declined) 2010 Air Force Office of Scientific Research Young Investigator Award 2015 National Institutes of Health Director's New Innovator Award 2016 HHMI-Simons Faculty Scholar Award 2020 Vilcek Prize for Creative Promise in Biomedical Science Martin Casimir Jonikas, Ph.D. -
Untying the Knot: Protein Quality Control in Inherited Cardiomyopathies
Pflügers Archiv - European Journal of Physiology https://doi.org/10.1007/s00424-018-2194-0 INVITED REVIEW Untying the knot: protein quality control in inherited cardiomyopathies Larissa M. Dorsch1 & Maike Schuldt1 & Dora Knežević1 & Marit Wiersma1 & Diederik W. D. Kuster1 & Jolanda van der Velden1 & Bianca J. J. M. Brundel1 Received: 30 July 2018 /Accepted: 6 August 2018 # The Author(s) 2018 Abstract Mutations in genes encoding sarcomeric proteins are the most important causes of inherited cardiomyopathies, which are a major cause of mortality and morbidity worldwide. Although genetic screening procedures for early disease detection have been improved significantly, treatment to prevent or delay mutation-induced cardiac disease onset is lacking. Recent findings indicate that loss of protein quality control (PQC) is a central factor in the disease pathology leading to derailment of cellular protein homeostasis. Loss of PQC includes impairment of heat shock proteins, the ubiquitin-proteasome system, and autophagy. This may result in accumulation of misfolded and aggregation-prone mutant proteins, loss of sarcomeric and cytoskeletal proteins, and, ultimately, loss of cardiac function. PQC derailment can be a direct effect of the mutation-induced activation, a compensa- tory mechanism due to mutation-induced cellular dysfunction or a consequence of the simultaneous occurrence of the mutation and a secondary hit. In this review, we discuss recent mechanistic findings on the role of proteostasis derailment in inherited cardiomyopathies, with special focus on sarcomeric gene mutations and possible therapeutic applications. Keywords Cardiomyopathy .Proteinqualitycontrol .Sarcomericmutation .Heatshockproteins .Ubiquitin-proteasomesystem . Autophagy Classification of cardiomyopathies occurring asymmetrically, and dilated CM (DCM), in which the presence of LV dilatation is accompanied by contractile Cardiomyopathies (CM) constitute one of the most common dysfunction [24]. -
Butterfly News We Looked at the Forehand Topspin with Both Feet Parallel to the Table
Official Equipment Supplier and Sponsor for the NEWS 2009 World Table Tennis Championships 2008 11 In this issue: Review EM 02 Europaen Championships St. Petersburg (Russia) St. Petersburg (Russia) Timo Boll shines with historical triumph in the Championships EM/WRL (10/08) 04 Timo Boll sets a monument for eternity in the EM-Interview 05 magnificent imperial city of St. Petersburg. Timo Boll The 27-year old German is the first player ever to defend every title (singles, doubles, Tips and Tricks 06 teams) of the European Championships in Werner Schlager: The double Belgrade last year since 1948. But that is not all: Along with the Swede Mikael Appelgren Butterfly-Inside 09 and his final opponent Vladimir Samsonov Shunsaku Yamada - Butterfly (Belarus) they each own three singles championship titles. If he wins another Interview 10 European Championship in Stuttgart next year, the two time World Cup champion could Richard Prause, Germany once again write table tennis history. More about on the next Page! Products of the month 12 Butterfly players account for 16 medals Global Collektion Technique Tips 13 The forhand topspin Butterfly-Inside 17 www.butterfly-world.com Butterfly-Academy Redaktion/Editor - Am Schürmannshütt 30h - D-47441 Moers - Germany - Phone: +49 2841 90532-0 - Mail: [email protected] 02 Preview European Championships European Championships in St. Petersburg Timo Boll shines with historical triumph in the Championships 19. November - 23. November 2008 The historical best note of 2008 goes along with a record setting conclusion of a Pro Tour: ERKE German Open, different kind. Players representing Butterfly scored their spots on the podium 16 Berlin times in six competitions. -
Chlamydia Trachomatis-Containing Vacuole Serves As Deubiquitination
RESEARCH ARTICLE Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense Annette Fischer1, Kelly S Harrison2, Yesid Ramirez3, Daniela Auer1, Suvagata Roy Chowdhury1, Bhupesh K Prusty1, Florian Sauer3, Zoe Dimond2, Caroline Kisker3, P Scott Hefty2, Thomas Rudel1* 1Department of Microbiology, Biocenter, University of Wu¨ rzburg, Wu¨ rzburg, Germany; 2Department of Molecular Biosciences, University of Kansas, lawrence, United States; 3Rudolf Virchow Center for Experimental Biomedicine, University of Wu¨ rzburg, Wu¨ rzburg, Germany Abstract Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique a-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl- 1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNg and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a *For correspondence: thomas. deubiquitinating activity exerting a function in selective stabilization of host proteins and [email protected]. protection from host defense. de DOI: 10.7554/eLife.21465.001 Competing interests: The authors declare that no competing interests exist. -
Quantifying Nucleation in Vivo Reveals the Physical Basis of Prion-Like Phase Behavior
bioRxiv preprint doi: https://doi.org/10.1101/205690; this version posted March 2, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Quantifying nucleation in vivo reveals the physical basis of prion-like phase behavior 1,3 1,3 1,2,3 1,3 1,3 Tarique Khan , Tejbir S. Kandola , Jianzheng Wu , Shriram Venkatesan , Ellen Ketter , 1 1 1 1 1 Jeffrey J. Lange , Alejandro Rodríguez Gama , Andrew Box , Jay R. Unruh , Malcolm Cook , 1,2, and Randal Halfmann * 1 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110 2 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA 3 These authors contributed equally *Corresponding author: [email protected] Highlights ● Distributed Amphifluoric FRET (DAmFRET) quantifies nucleation in living cells ● DAmFRET rapidly distinguishes prion-like from non-prion phase transitions ● Nucleation barriers allow switch-like temporal control of protein activity ● Sequence-intrinsic features determine the concentration-dependence of nucleation barriers Summary Protein self-assemblies modulate protein activities over biological time scales that can exceed the lifetimes of the proteins or even the cells that harbor them. We hypothesized that these time scales relate to kinetic barriers inherent to the nucleation of ordered phases. To investigate nucleation barriers in living cells, we developed Distributed Amphifluoric FRET (DAmFRET). DAmFRET exploits a photoconvertible fluorophore, heterogeneous expression, and large cell numbers to quantify via flow cytometry the extent of a protein’s self-assembly as a function of cellular concentration. -
11/05/09 Agenda Attachment 6
Bioinformatics @ UCSF: Faculty Multidisciplinary graduate study in biological composition, structure, David Agard function and evolution at the [email protected] molecular and systems levels Professor, Biochemistry & Biophysics Apply Now Structure, function, and folding of proteins, chromosomes, and About the Program centrosomes Training Program: Program Overview Core Curriculum Nadav Ahituv Electives [email protected] Seminars & Journal Club Assistant Professor, Bioengineering and Therapeutic Sciences Academic Progression & Procedures Deciphering the role of gene regulatory sequences in human People: biology and disease Students Faculty Alumni Patricia Babbitt Current Events [email protected] Admission Information Professor, Bioengineering and Therapeutic Sciences and Links Pharmaceutical Chemistry Contact Computational and experimental analysis of protein NEWS: UCSF wins HHMI Award for its superfamilies for functional inference and enzyme design Integrative Program in Complex Biological Systems Bruce Conklin [email protected] Associate Professor, Gladstone Institute of Cardiovascular Disease, Medicine & Pharmacology Combining the tools of molecular biology, genetics, bioinformatics, and physiology to answer fundamental issues in pharmacology. Joe DeRisi [email protected] Hughes Investigator, Associate Professor, Biochemistry & Biophysics Malaria gene expression profiling, functional genomics, microarrays Ken Dill [email protected] Professor, Pharmaceutical Chemistry Statistical mechanics of biomolecules, protein -
Proteasomes: Unfoldase-Assisted Protein Degradation Machines
Biol. Chem. 2020; 401(1): 183–199 Review Parijat Majumder and Wolfgang Baumeister* Proteasomes: unfoldase-assisted protein degradation machines https://doi.org/10.1515/hsz-2019-0344 housekeeping functions such as cell cycle control, signal Received August 13, 2019; accepted October 2, 2019; previously transduction, transcription, DNA repair and translation published online October 29, 2019 (Alves dos Santos et al., 2001; Goldberg, 2007; Bader and Steller, 2009; Koepp, 2014). Consequently, any disrup- Abstract: Proteasomes are the principal molecular tion of selective protein degradation pathways leads to a machines for the regulated degradation of intracellular broad array of pathological states, including cancer, neu- proteins. These self-compartmentalized macromolecu- rodegeneration, immune-related disorders, cardiomyo- lar assemblies selectively degrade misfolded, mistrans- pathies, liver and gastrointestinal disorders, and ageing lated, damaged or otherwise unwanted proteins, and (Dahlmann, 2007; Motegi et al., 2009; Dantuma and Bott, play a pivotal role in the maintenance of cellular proteo- 2014; Schmidt and Finley, 2014). stasis, in stress response, and numerous other processes In eukaryotes, two major pathways have been identi- of vital importance. Whereas the molecular architecture fied for the selective removal of unwanted proteins – the of the proteasome core particle (CP) is universally con- ubiquitin-proteasome-system (UPS), and the autophagy- served, the unfoldase modules vary in overall structure, lysosome pathway (Ciechanover, 2005; Dikic, 2017). UPS subunit complexity, and regulatory principles. Proteas- constitutes the principal degradation route for intracel- omal unfoldases are AAA+ ATPases (ATPases associated lular proteins, whereas cellular organelles, cell-surface with a variety of cellular activities) that unfold protein proteins, and invading pathogens are mostly degraded substrates, and translocate them into the CP for degra- via autophagy. -
Presumption of Guilt the Global Overuse of Pretrial Detention Presumption of Guilt: the Global Overuse of Pretrial Detention Copyright © 2014 Open Society Foundations
Presumption of Guilt The Global Overuse of Pretrial Detention Presumption of Guilt: The Global Overuse of Pretrial Detention Copyright © 2014 Open Society Foundations. This publication is available as a pdf on the Open Society Foundations website under a Creative Commons license that allows copying and distributing the publication, only in its entirety, as long as it is attributed to the Open Society Foundations and used for noncommercial educational or public policy purposes. Photographs may not be used separately from the publication. ISBN: 978-1-936133-84-0 PUBLISHED BY: Open Society Foundations 224 West 57th Street New York, New York 10019 USA www.OpenSocietyFoundations.org FOR MORE INFORMation contact: Martin Schönteich Senior Legal Officer Criminal Justice Program [email protected] Design and layout by John Emerson, backspace.com and Heather Van De Mark, heathervandemark.com Printed by GHP Media, Inc. Cover photo © Benedicte Kurzen/NOOR for the Open Society Foundations Table of Contents Acknowledgments i Executive Summary & Recommendations 1 Introduction 7 The Scope of Pretrial Detention Around the World: Its Extent and Cost 11 Introduction 11 The Extent of Pretrial Detention 15 The Cost of Pretrial Detention 28 Conclusion 31 Who Are the World’s Pretrial Detainees? 33 Introduction 33 The Poor 33 Marginalized Minorities and Non-Citizens 49 The Mentally Ill and Intellectually Disabled 51 Low-Risk Defendants, Persons Accused of Minor Offenses, and the Innocent 53 Conclusion 55 Circumstances of Detention and -
Ubiquitin-Dependent Folding of the Wnt Signaling Coreceptor LRP6
RESEARCH ARTICLE Ubiquitin-dependent folding of the Wnt signaling coreceptor LRP6 Elsa Perrody1†, Laurence Abrami1†, Michal Feldman1, Beatrice Kunz1, Sylvie Urbe´ 2, F Gisou van der Goot1* 1Global Health Institute, Ecole Polytechnique Fe´de´rale de Lausanne, Lausanne, Switzerland; 2Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Abstract Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. This ubiquitination-deubiquitination is conceptually reminiscent of the glucosylation-deglucosylation occurring in the ER lumen during the calnexin/ calreticulin folding cycle. To avoid infinite futile cycles, folded LRP6 molecules undergo palmitoylation and ER export, while unsuccessfully folded proteins are, with time, polyubiquitinated on other lysines and targeted to degradation. This ubiquitin-dependent folding system also controls the proteostasis of other membrane proteins as CFTR and anthrax toxin receptor 2, two poor folders involved in severe human diseases. DOI: 10.7554/eLife.19083.001 *For correspondence: gisou. [email protected] Introduction † These authors contributed While protein folding may be extremely efficient, the presence of multiple domains, in soluble or equally to this work membrane proteins, greatly reduces the efficacy of the overall process. Thus, a set of enzymes and Competing interests: The chaperones assist folding and ensure that a sufficient number of active molecules reach their final authors declare that no destination (Brodsky and Skach, 2011; Ellgaard et al., 2016). -
The Life of Proteins: the Good, the Mostly Good and the Ugly
MEETING REPORT The life of proteins: the good, the mostly good and the ugly Richard I Morimoto, Arnold J M Driessen, Ramanujan S Hegde & Thomas Langer The health of the proteome in the face of multiple and diverse challenges directly influences the health of the cell and the lifespan of the organism. A recent meeting held in Nara, Japan, provided an exciting platform for scientific exchange and provocative discussions on the biology of proteins and protein homeostasis across multiple scales of analysis and model systems. The International Conference on Protein Community brought together nearly 300 scientists in Japan to exchange ideas on how proteins in healthy humans are expressed, folded, translocated, assembled and disassembled, and on how such events can go awry, leading to a myriad of protein conformational diseases. The meeting, held in Nara, Japan, in September 2010, coincided with the 1,300th birthday of Nara, Japan’s ancient capital, and provided a meditative setting for reflecting on the impact of advances in Nature America, Inc. All rights reserved. All rights Inc. America, Nature protein community research on biology and 1 1 medicine. It also provided an opportunity to consider the success of the protein community © 20 program in Japan since meetings on the stress response (Kyoto, 1989) and on the life of proteins (Awaji Island, 2005). The highlights and poster presentations. During these socials, and accessory factors. Considerable effort has of the Nara meeting were, without question, graduate and postdoctoral students and all of been and continues to be devoted toward the social periods held after long days of talks the speakers sat together on tatami mats at low understanding the mechanistic basis of protein tables replete with refreshments and enjoyed maturation and chaperone function. -
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Editor in Chief: Yoshiki Hamada, Tsurumi University, Japan Oral and Maxillofacial Surgery Section Oral Medicine Section Section Editor Section Editor Yoshiki Hamada, Tsurumi University, Japan Gen-Yuki Yamane, Tokyo Dental College, Japan Associate Editors Associate Editors Yoshiko Ariji, Aichi Gakuin University, Japan Jong-Hoo Choi, Yonsei University, Korea Jong-Ho Lee, Seoul National University, Korea Yoshimasa Kitagawa, Hokkaido University, Japan Chung-Ji Liu, National Yang Ming University, Chinese-Taipei Eiro Kubota, Kanagawa Dental College, Japan Seiji Nakamura, Kyushu University, Japan Kazuhito Satomura, Tsurumi University, Japan Akira Sasaki, Okayama University, Japan Tetsu Takahashi, Tohoku University, Japan Editorial Board Members Guang-Yan Yu, Peking University, China Ashish Aggarwal, Institute of Dental Sciences, India Takashi Fujibayashi, Kanagawa Dental College, Japan Editorial Board Members Michael Glick, University at Buffalo, USA Nihal Asoka de Silva Amaratunga, University of Peradeniya, Yoshiki Imamura, Nihon University, Japan Sri Lanka Hong-Seop. Kho, Seoul National University, Korea Izumi Asahina, Nagasaki University, Japan Mikio Kusama, Jichi Medical University, Japan Michael Yuanchien Chen, China Medical University Hospital, Peter B. Lockhart, Carolinas HealthCare Foundation, USA Chinese-Taipei Takashi Sasano, Tohoku University, Japan Lim K Cheung, Hong Kong University, Hong Kong Kobkan Thongprasom, Chulalongkorn University, Thailand Wei-Fan Chiang, -
Biochemical Analysis of a Prokaryotic Deubiquitinase from Escherichia Coli Cameron Wade Purdue University
Purdue University Purdue e-Pubs Open Access Theses Theses and Dissertations January 2016 Biochemical Analysis of a Prokaryotic Deubiquitinase from Escherichia Coli Cameron Wade Purdue University Follow this and additional works at: https://docs.lib.purdue.edu/open_access_theses Recommended Citation Wade, Cameron, "Biochemical Analysis of a Prokaryotic Deubiquitinase from Escherichia Coli" (2016). Open Access Theses. 1233. https://docs.lib.purdue.edu/open_access_theses/1233 This document has been made available through Purdue e-Pubs, a service of the Purdue University Libraries. Please contact [email protected] for additional information. *UDGXDWH6FKRRO)RUP 8SGDWHG PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance 7KLVLVWRFHUWLI\WKDWWKHWKHVLVGLVVHUWDWLRQSUHSDUHG %\ Cameron Wade (QWLWOHG BIOCHEMICAL ANALYSIS OF A PROKARYOTIC DEUBIQUITINASE FROM ESCHERICHIA COLI Master of Science )RUWKHGHJUHHRI ,VDSSURYHGE\WKHILQDOH[DPLQLQJFRPPLWWHH Chittaranjan Das Jean-Christophe Rochet Andrew D. Mesecar Mark C. Hall To the best of my knowledge and as understood by the student in the Thesis/Dissertation Agreement, Publication Delay, and Certification/Disclaimer (Graduate School Form 32), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy on Integrity in Research” and the use of copyrighted material. Chittaranjan Das $SSURYHGE\0DMRU3URIHVVRU V BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB $SSURYHGE\Timothy Zwier 04/21/2016 +HDGRIWKH'HSDUWPHQW*UDGXDWH3URJUDP 'DWH BIOCHEMICAL ANALYSIS