Molecular Bases of Proteinopathies
2020-2022 virtual meeting of talks and discussion on "protein multimerization: the good, bad, and exciting aspects"
The ZOOMinar series on “Molecular Basis of Proteinopathies” will cover recent breakthroughs in this exciting multidisciplinary area of research from experts in the field. When conferences have been canceled around the world, these virtual presentations and discussions will provide unique opportunities for everyone to learn about recent findings, new topics, and cutting-edge techniques. The live presentations are on Tuesdays (August 2020) and Saturdays (from September 2020 to August 2021) from 10:00 AM to ~11:00 AM (EDT); and Mondays (from October 2021 onwards) from 12:00 noon EST/EDT. This virtual seminar includes a ~35 minutes presentation and ~15 minutes for questions and answers. This series has >1000 registered participants from all over the world. The virtual presentations will be recorded and made available on a YouTube channel (search for the "amyloid symposium").
Organizers
Ayyalusamy (Rams) RamamoorthyBiophysics and Chemistry, University of Michigan
Email: ramamoor@umich.edu
Joan Shea, Chemistry and Biochemistry & Physics, University of California Santa Barbara
Email: shea@ucsb.edu
Magda Ivanova, Department of Neurology, University of Michigan
Email: mivanova@umich.edu
Samuel McCalpin, Chemistry, University of Michigan
Email: mcsamuel@umich.edu
If you are an expert in the following area(s) and wish to give a talk, please contact us.
Molecular aspects of amyloid toxicity
Molecular events in the gut-brain connection
Amyloid propagation in the brain
Experimental structures of non-fibril amyloid species
Invited Speakers
April 24, 2023
Dr. Kanchan Garai
Tata Institute of Fundamental Research, Hyderabad, India
"Investigation of amyloid aggregation using single molecule fluorescence techniques"
April 24, 2023
Dr. Sason Shaik
The Hebrew University, Israel
"Assessing the Potentials of Static vs. Oscillating Electric Fields to Decompose Senile Plaques"
April 17, 2023
Dr. Burkhard Bechinger
University of Strasbourg, France
"Lipid-driven assembly of polypeptide complexes"
April 17, 2023
Dr. Santosh Kumar Jha
CSIR-National Chemical Laboratory, Pune, India
"Mechanistic insights into the stress-induced aggregation of
TDP-43 in ALS"
April 17, 2023
Dr. Rizwan Khan
Aligarh Muslim University, India
"Amyloid Induction and Inhibition"
April 17, 2023
Dr. Burkhard Bechinger
University of Strasbourg, France
"TBD"
April 10, 2023
Dr. Sapun Parekh
University of Texas, Austin
"Heterogeneous structures (and order) of disordered FUS condensation"
April 10, 2023
Dr. Nikolay Dokholyan
Penn State University College of Medicine
"Molecular Etiologies of Neurodegeneration"
April 03, 2023
Dr. Tang Ben Zhong
The Hong Kong University of Science & Technology (HKUST),
Hong Kong, China
"TBD"
April 03, 2023
Dr. Wei Qiang
Binghamton University
"Cross-Seeding Between Beta-Amyloid Variants In-Vitro and In Cells"
March 27, 2023
Dr. Yoh Matsuki
Osaka University, Japan
March 27, 2023
Dr. Jing Xu
University of California Merced
"How do molecular motors overcome tau inhibition to maintain cargo transport?"
March 20, 2023 CANCELLED
Dr. Ellen Nollen
European Research Institute for the Biology of Ageing,
University of Groningen, Netherlands
"TBD"
March 20, 2023 CANCELLED
Dr. Samuel Grant
National High Magnetic Field Lab, Florida State University, & FAMU
"TBD"
March 13, 2023 (*8:00 AM, New York time)
Dr. Kenji Sugase
Kyoto University
"Multiple-State Monitoring of SOD1 Amyloid Formation at Single-Residue Resolution by Rheo-NMR Spectroscopy"
March 13, 2023 (*8:00 AM, New York time)
Dr. Heather Wilkins
University of Kansas
"Amyloid Precursor Protein and Mitochondria"
March 06, 2023 (*8:00 AM, New York time)
Dr. Ashutosh Tiwari
Michigan Technological University, Houghton
"Protein Aggregates and Cellular Toxicity:
What is the Connection?"
March 06, 2023 (*8:00 AM, New York time)
Dr. Xin Zhang
Westlake University, China
"New Methods to Visualize Protein Aggregation in Live Cells"
February 27, 2023 (*8:00 AM, New York time)
Dr. Kazhuhiro Irie
Graduate School of Agriculture, Kyoto University, Japan
"Synthesis and Characterization of Dimer and Trimer Models of Amyloid β40 Tethered at the C-Terminal Region"
February 27, 2023 (*8:00 AM, New York time)
Dr. Erwan Bezard
CNRS, France
"Towards modeling of proteinopathies in non-human primates"
February 20, 2023 (*8:00 AM, New York time)
Dr. Katsumi Matsuzaki
Kyoto University, Japan
"How do membranes initiate Alzheimer's Disease?"
February 20, 2023 (*8:00 AM, New York time)
Dr. Yoshitaka Ishii
Tokyo Institute of Technology, Japan
"Structures and Misfolding Kinetics of Amyloid-beta Fibrils Studied by Solid-state NMR and CryoEM"
February 13, 2023 (*8:00 AM, New York time)
Dr. Tomohide Saio
Tokushima University, Japan
"NMR investigation of the regulators in protein folding and assembly"
February 13, 2023
(*8:00 AM, New York time)
Dr. Takaomi Saido
RIKEN Center for Brain Science, Japan
"GPCR-based treatment of preclinical Alzheimer’s disease"
February 06, 2023 (*8:00 AM, New York time)
Dr. Masaki Okumura
Tohoku University, Japan
"Understanding the mechanism by which Protein Disulfide Isomerase (PDI) family guide proper oxidative folding"
February 06, 2023 (*8:00 AM, New York time)
Dr. Takahiro Murakoa
Tokyo University of Agriculture and Technology
Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan
"Functional assembly of polypeptides for injured brain regeneration"
January 30, 2023 (*8:00 AM, New York time)
Dr. Human Rezaei
CNRS, France
"Toward a link between the dynamic of prion replication, prion evolution and tissue spreading"
January 30, 2023 (*8:00 AM, New York time)
Dr. Sven Saupe
CNRS, University of Bordeaux, France
"Amyloid signaling motifs in fungal and bacterial regulated cell death pathways"
January 23, 2023 (*8:00 AM, New York time)
Dr. Emma Sparr
Lund University, Sweden
"Decorated vesicles- Interactions between α-synuclein
and lipid membranes"
January 23, 2023 (*8:00 AM, New York time)
Dr. Loren Andreas
Max Planck Institute, Göttingen, Germany
"Structure of a lipidic alpha-Synuclein aggregation intermediate"
January 16, 2023 (*8:00 AM, New York time)
Dr. Gunnar Schroeder
Forschungszentrum Jülich
"Cryo-EM Studies of Amyloid Fibrils"
January 16, 2023 (*8:00 AM, New York time)
Dr. Ronald Melki
CNRS, France
"Alpha-synuclein fibrillar aggregates polymorphism and distinct synucleinopathies"
January 09, 2023 (*8:00 AM, New York time)
Dr. Per Westermark
Uppsala University, Sweden
"Type A and Type B fibrils in transthyretin (ATTR) amyloidosis"
January 09, 2023 (*8:00 AM, New York time)
Dr. Marie Doumic
Inria, CNRS and Sorbonne Université, France
"Mathematical Modelling for Protein Polymerisation: Results and Open Questions"
December 12, 2022
Dr. Francois-Xavier Theillet
CNRS, France
"Atomic scale analysis of IDPs expressed in live mammalian cells, using in-cell NMR at 310 K"
December 12, 2022
Dr. Tae Hun Kim
University of Toronto (Canada),
Case Western Reserve University, Cleveland (USA)
"Elucidating protein-protein interactions within phase-separated droplets by NMR"
December 05, 2022
Dr. Liliana Quintanar
Cinvestav (Center for Research and Advanced Studies),
Mexico City, México
"Metal ions and protein aggregation: From the brain to the human lens"
December 05, 2022
Dr. Christiano L. Dias
New Jersey Institute of Technology
"Lipid Membrane Damage by Amyloid-Like Peptides: Insights from Unbiased All-Atom Simulations "
November 28, 2022
Dr. Pau Bernado
Center for Structure Biology, Montpellier, France
"Structure of Pathogenic Huntingtin Exon-1"
November 28, 2022
Dr. Vijay Rangachari
University of Southern Mississippi
"Alpha-Synuclein induced heterotypic fibril polymorphs of TDP-43"
November 21, 2022
Dr. Axel Abelein
Karolinska Institutet, Sweden
"Molecular mechanisms of metal ion modulation of amyloid-beta aggregation"
November 14, 2022
Dr. Andela Saric
Institute of Science and Technology, Austria
"Physics of amyloid self-replication and inhibition"
November 14, 2022
Dr. Neville Vassallo
University of Malta
"Mitochondrial poration by amyloidogenic peptides"
November 07, 2022
Dr. Frederic Rousseau
Switch Laboratory,
Katholieke Universiteit Leuven, Belgium
"Heterotypic amyloid interactions modulate amyloid assembly and structure"
November 07, 2022
Dr. Wenwei Zheng
Arizona State University
"Computational methods for interpreting intrinsically disordered protein interactions"
October 31, 2022
Dr. Francesco Simone Ruggeri
Wageningen University
"Ultrastructural Characterisation of Amyloid Formation One Molecule at a Time"
October 31, 2022
Dr. Ruiqing Ni
University of Zurich, Switzerland
"Non-invasive imaging of amyloid-beta and tau"
October 24, 2022
Dr. Thomas Michaels
Department of Biology, Institute of Biochemistry,
ETH Zurich, Switzerland
"Control of protein aggregation"
October 24, 2022
Dr. Daniel Raleigh
Stony Brook University,
"Amylin (IAPP) Induced b-cell Death: From Molecular Biophysics to Potential Therapeutic Applications"
October 17, 2022
Dr. Sara Linse
Lund University,
Sweden
"Secondary nucleation in amyloid formation"
October 17, 2022
Dr. Minkoo Ahn
Institute of Structural and Molecular Biology,
University College London, UK
"Modulating co-translational protein folding by rational design and ribosome engineering"
October 10, 2022
Dr. Ken Dill
Stony Brook University
"The biophysics of protein aggregation"
October 03, 2022
Dr. Aaron Wilber
Florida State University,
"A Parietal-Hippocampal Network for Figuring Out Where You Are And What to Do Next is Dysfunctional in AD"
September 26, 2022
Dr. Hilal Lashuel
EPFL, Switzerland
"Revisiting the grammar of Huntingtin aggregation, inclusion formation
and toxicity in Huntington’s disease"
September 26, 2022
Dr. Antoine Loquet
University of Bordeaux
"Amyloids in signalling processes as seen by solid-state NMR"
September 19, 2022
Dr. Stefan Rüdiger
University of Utrecht
"Chaperoning protein aggregation diseases "
September 12, 2022
Dr. Wei-Feng Xue
University of Kent,
UK
"The polymorphic landscape of amyloid assembly revealed by AFM and individual particle structural reconstruction"
September 12, 2022
Dr. Per Hammarström
Linköping University
"Amyloid polymorphism in neurodegenerative disease"
July 25, 2022
Dr. Rebecca Berlow
University of North Carolina at Chapel Hill
"Rewriting the Rules of Molecular Competition: Transcriptional Regulation by Intrinsically Disordered Proteins"
July 25, 2022
Dr. Hariom Yadav
University of South Florida
"Role of Microbiome and Its Modulators in Maintaining Our Brain Health"
July 18, 2022
Dr. Marina Ramirez-Alvarado
Mayo Clinic
"When antibodies misbehave, misfold, and kill - the biophysics of aggregation, toxicity, and rescue in vitro and in cell culture"
July 11, 2022
Dr. Ujjayini Ghosh
University of California, San Francisco
"Integrated Cryo-EM and Solid-state NMR Structure of Amyloid-β Fibrils from Alzheimer’s Disease Brain"
July 11, 2022
Dr. Wolfgang Hoyer
Heinrich Heine University Düsseldorf,
Germany
"Formation and interactions of metastable
Aβ oligomers"
June 27, 2022
Sara Linse, Steve Bourgault, Sandrine Ongeri, Lucie Khemtemourian, Samuel McCalpin
"Good, Bad, and Ugly Aspects of Thioflavin-T"
June 20, 2022
Dr. Irving Vega
Michigan State University
"Modulators of tau protein dynamics: from toxic to less toxic"
June 20, 2022
Dr. Martina Pannuzzo
Instituto Italiano di Technologia,
Italy
"A combined theoretical and computational approach to disentangle the molecular events at the intersection of amyloid pore and fibrils formation"
June 13, 2022
Dr. Paolo Arosio
ETH,
Zurich
"Interplay between condensation and amyloid formation"
June 13, 2022
Dr. Tom Rothstein
Western Michigan University
"My Quarter Century of FameFAIM"
June 06, 2022
Dr. Yoshitaka Ishii
Tokyo Institute of Technology, Japan
"Solid-state NMR studies highlight structural differences and cross-seeding properties of amyloid-beta fibrils"
June 06, 2022
Dr. Pernilla Wittung-Stafshede
Chalmers University of Technology,
Sweden
"Cross-reactivity of Parkinson’s disease protein alpha-synuclein:
Consequences for amyloid formation"
May 30, 2022
Dr. Cláudio Gomes
Faculdade de Ciências da Universidade de Lisboa, Portugal
"Modulators of protein aggregation and toxicity in neurodegenerative diseases"
May 30, 2022
Dr. Dave Klenerman
University of Cambridge, UK
"Charactersing the protein aggregates formed in humans during the development of neurodegenerative disease"
May 23, 2022
Dr. Guido Pintacuda
Lyon University, France
"Conformational dynamics by NMR in crystals: a tool for detection aggregation propensity of folded and soluble proteins"
May 23, 2022
Dr. Jinghui Luo
Laboratory of Nanoscale Biology, Paul Scherrer Institute, Switzerland
"Transmembrane protein engineering for studying amyloid proteins "
May 16, 2022
Dr. Jun-Xia Lu
ShanghaiTech University, China
"The Amyloid Structures in Cell Necroptosis"
May 16, 2022
Dr. Thimmaiah Govindaraju
Jawaharlal Nehru Centre for Advanced Scientific Research, India
"Alzheimer’s Disease:
Pathophysiology, diagnostic and therapeutic modalities"
May 09, 2022
Dr. Eri Chatani
Kobe University, Japan
"Investigating protein assembly in the nucleation of amyloid fibrils"
May 09, 2022
Dr. James Shorter
University of Pennsylvania, Philadelphia
"Countering deleterious phase transitions in ALS/FTD"
May 02, 2022
Dr. Michele Vendruscolo
University of Cambridge, UK
"Kinetics-Based Drug Discovery for Neurodegenerative Diseases"
May 02, 2022
Dr. Joel Watts
University of Toronto, Canada
"Strains of Pathological Protein Aggregates in Neurodegenerative Diseases"
April 25, 2022
Dr. Michael Heneka
University of Bonn Medical Center, Germany
"TBD"
Dr. Daniel Raleigh
Stony Brook University
"TBD"
April 18, 2022
Dr. Avindra Nath
NIH
"Aggregates of HIV-Tat protein complexed with amyloid beta peptide accelerate neurodegeneration"
Dr. Gal Bitan
UCLA
"Discovery of exophers in mammalian neurons - implications for brain health and disease"
April 11, 2022
Dr. Takahiro Watanabe-Nakayama
Kanazawa University
Japan
"Single molecule observation of amyloid aggregation"
Dr. Guido Pintacuda
Lyon University, France
"Conformational dynamics by NMR in crystals: a tool for detection aggregation propensity of folded and soluble proteins"
April 04, 2022
Dr. Dylan Murray
University of California, Davis
"Low complexity protein domain assembly mechanisms"
April 04, 2022
Dr. Henry Paulson
University of Michigan, Ann Arbor
"TBD"
March 28, 2022
Dr. Daniel Huster
Institut für Medizinische Physik und Biophysik, Leipzig, Germany
"The Structure and Dynamics of Mutated Amyloid β Fibrils"
March 28, 2022
Dr. Olga Gursky
Boston University
"Protein amyloid cofactors: Charged side chain arrays meet their match"
March 21, 2022
Dr. Sandrine Ongeri
&
Dr. Nicolo Tonali
CNRS, Université Paris Saclay, France
"Folded peptidomimetics based on cross-interactions involved in the prevention of amyloid proteins aggregation"
March 14, 2022
Dr. Robert Tycko
NIH
"Structures and Structural Variations in Amyloid Fibrils (Amyloid-beta and Others): Insights from Solid State NMR and Electron Microscopy"
March 14, 2022
Dr. Antoine Loquet
University of Bordeaux
"Amyloids in signalling processes as seen by solid-state NMR"
March 07, 2022
Dr. Nicolas Fawzi
Brown University
"Using NMR spectroscopy to see RNA-binding protein phase separation and aggregation"
March 07, 2022
Dr. James Nowick
University of California, Irvine
"Exploring Amyloid Oligomers with Macrocyclic β-Sheet Peptides"
Presentations from Early Career Researchers - a mini-symposium (March 05, 2022, from 10:00 AM EST)
Organizers of the ZOOMinar series invite early career researchers (students and post-doctoral fellows) to present their research related to "High-resolution (experimentally determined) structures of amyloid proteins". The goal is to provide opportunities for early-career researchers to present their latest research findings, interact with experts with multidisciplinary expertise, and gain critical feedback and collaborations.
To be considered for a short presentation in the ZOOMinar series, you will need to email a title, reference to a published paper, and graphics (or TOC figure) by Dec. 01, 2021. Emails: ramamoor@umich.edu; mivanova@umich.edu
*Additional details about this mini-symposium will be provided later.
Panel: Samuel McCalpin (Michigan), Anoop Arunagiri (Michigan), Samuel Kotler (NIH)
Speakers:
David Boyer, UCLA, "Hereditary mutations, hydrogels, small molecule binding, unexpected sequences: what we are learning from cryoEM structures of amyloid fibrils"
Linda Cerofolini, CERM, Florence, Italy. "Mixing Aβ(1-40) and Aβ(1-42) peptides generates unique amyloid fibrils"
Pijush Chakraborty, German Center for Neurodegenerative Diseases, Göttingen, Germany, "Co-factor-free aggregation of tau into seeding-competent RNA-sequestering amyloid fibrils"
Aurelio Dregni, Chemistry, MIT, USA, "Inclusion of the C-Terminal Domain in the beta-Sheet Core of Heparin-Fibrilized 0N3R Tau Revealed by Solid-State NMR"
Rodrigo Gallardo, University of Leeds, UK, "Cryo-EM unveils the dramatic effect of a single amino acid substitution in the structure of amyloid fibrils. The case of IAPP and its S20G variant"
Myungwoon Lee, Laboratory of Chemical Physics Lab, NIDDK, NIH, USA, "FUS low complexity domain fibril structure by Cryo-electron microscopy and solid-state NMR"
Ryan McGlinchey, NHBLI, NIH, USA, "Effect of N- and C-terminal Truncations on α-Synuclein Amyloid Formation and Fibril Structure"
Yang Shi, MRC Laboratory of Molecular Biology, Cambridge, UK, "Structure-based Classification of Tauopathies"
Yunpeng Sun, Shanghai Jiao Tong University, China, "The structural basis of amyloid aggregation of ALS-associated pathological proteins"
Victoria Trinkaus, Max Planck Institute of Biochemistry in Martinsried, Germany, "In-situ architecture of neuronal alpha-synuclein inclusions"
Marielle Wälti, ETH, Switzerland, "Atomic-resolution structure of a disease-relevant Abeta(1-42) amyloid fibril"
Kun Zhao, Shanghai Institute of Organic Chemistry, China, "Investigating the role of PTM on alpha-synuclein amyloid fibril structure and pathology"
Feb. 28, 2022
Dr. Kenjiro Ono
Department of Neurology
Kanazawa University, Japan
"HMW Aβ oligomers are important targets for disease modifying approach of Alzheimer's disease"
Feb. 28, 2022
Dr. Justin Legleiter
West Virginia University
"Huntingtin aggregation in the presence of lipid membranes: Implications for Huntington’s disease"
Feb. 21, 2022
Dr. Alexander Kai Büll
Technical University of Denmark
"Thermodynamics of amyloid fibril formation"
Feb. 21, 2022
Dr. Shai Rahimipour
Bar-Ilan University, Israel
"Toward Early Diagnosis and Therapy of Alzheimer's Disease"
Feb. 14, 2022
Dr. Claudio Luchinat
CERM, Florence, Italy
"Molecular Aspects of Protein Aggregation"
Feb. 14, 2022
Dr. Raz Jelinek
Ben-Gurion University, Israel
"Natural amyloid fibrils as catalysts of physiological and pathological reactions: a new paradigm in disease?"
Feb. 07, 2022
Dr. Andisheh Abedini
Stonybrook University
"Cellular mechanisms of IAPP-induced islet β-cell dysfunction in diabetes"
Feb. 07, 2022
Dr. Ralf Langen
University of Southern California
"Conformationally Specific Huntingtin Binders as Potential Biomarkers or Therapeutics"
Jan. 31, 2022
Dr. Ioana Mariuca Ilie
University of Amsterdam
"Antibody binding modulates the dynamics of the cellular prion protein"
Jan. 31, 2022
Dr. Amedeo Caflisch
University of Zurich
"Kinetic control of fibril formation and design of antiprion compounds"
January 24, 2022
Dr. Fabrizio Chiti
University of Florance, Italy
"Physicochemical basis of the displacement of amyloidogenic proteins and misfolded protein oligomers from biological membranes"
January 24, 2022
Dr. Jin Hyung Lee
Stanford University
"Illuminating neural circuits: from molecules to MRI for precision brain health"
January 17, 2022
Dr. Christopher Martyniuk
University of Florida
"Zebrafish as a model to understand pesticide-induced neurotoxicity: Relevance to Parkinson's disease"
Dr. Matthias Buck
Case Western Reserve University
"NMR and Molecular Dynamics Studies on Protein-Protein Interactions: Examples from the Class of Dynamic Protein Complexes"
January 10, 2022
Dr. Rohit Pappu
Washington University, St.Louis
"Linkage of folding and binding on phase separation"
December 13, 2021
Dr. Pu-Chen Ke
Monash University, Australia
"Mitigating amyloidogenesis with nanomaterials"
December 13, 2021
Dr. Jeremy Schmit
Kansas State University,
"The landscape of amyloid misfolding"
December 06, 2021
Dr. Eitan Lerner
Hebrew University, Israel
"Integrative studies of the structural dynamics of alpha-Synuclein forms"
December 06, 2021
Dr. Gregory Hudalla
University of Florida
"Form and Function of Glycosylated Peptide Nanofibers"
November 29, 2021
Professor Eric Brown
McMaster University, Canada
"Bugs, drugs and cell systems"
November 22, 2021
Dr. Sami Barmada
University of Michigan
"Autophagy and cell type-specific factors regulating autophagy in neurodegenerative disease models"
November 22, 2021
Dr. Céline Galvagnion-Büll
University of Copenhagen
"Alpha-synuclein – membrane interactions: the influence of lipid composition on the kinetics of protein aggregation"
November 15, 2021
Professor Dr. Marcus Faendrich
Ulm University, Germany
"Cryo-EM structures of ex vivo amyloid fibrils"
November 01, 2021
Professor Roland Riek
ETH
"Amyloids: from the origin to end of life"
November 01, 2021
Professor Anant Paravastu
Georgia Institute of Technology
"Structural Studies of Alzheimer’s Amyloid-β Oligomers: why would a β-sheet peptide aggregate be limited in size?"
October 04, 2021 Dr. Dennis J. Selkoe
August 21, 2021
Gary Lorigan
Professor, Miami University, Ohio
https://blogs.miamioh.edu/lorigan-research-group/
Annelise E. Barron
Associate Professor
Department of Bioengineering
Stanford University
August 4, 2020
A Hypothesis for How Innate Immune Dysregulation May Cause Alzheimer’s Dementia;
and How We May Be Able to Prevent It
We are investigating the early-stage etiology of sporadic Alzheimer's Disease (AD), for which 420+ clinical trials by Pharma have failed over the past 15 years to produce an effective drug. What causes the accumulation of Aβ peptide-rich fibrils and plaques in an aging brain? What are Aβ's physiological functions? We focus on Aβ's interactions with the human cathelicidin peptide, LL-37, an antibacterial and antiviral innate immune system effector and modulator that is ubiquitous in tissues and expressed by myriad cell types, yet unique in the human proteome. Recently, evidence has built that chronic Herpesvirus or P. gingivalis infections of human brain tissue may precipitate many cases of sporadic dementia labeled as Alzheimer’s Disease. We present experimental evidence and discuss our developing hypothesis that the antiviral and antibacterial peptide LL-37, which can be chronically under-expressed in humans based on dietary and lifestyle factors or degraded by P. gingivalis virulence factors, is a natural binding partner of Aβ that inhibits formation of AD fibrils and plaques, such that LL-37 and Aβ have a toxin/antitoxin relationship. We demonstrate binding between LL-37 and Aβ by Transmission Electron Microscopy (TEM), Surface Plasmon Resonance Imaging (SPRi), and circular dichroism (CD) spectroscopy. TEM shows that LL-37 inhibits the fibrillization of Aβ, especially the formation of long, straight fibrils characteristic of AD, while CD spectroscopy reveals that LL-37 binding prevents Aβ from adopting β-type secondary structure. Analytical Ultracentrifugation (AUC) and Small-Angle X-ray Scattering (SAXS) prove that LL-37 and Aβ form a unique, water-soluble, 1:1 complex. In vitro cell culture studies using primary human microglia and neuronal cells indicates that these two peptides neutralize each other’s cytotoxic effects on these cells. Finally, studies in 5XFAD and wildtype transgenic mice, and Drosophila Melanogaster, support these findings. We discuss what all of this means in the context of the prevention and treatment of Alzheimer’s dementia.
Rakez Kayed
Professor
Department of Neurology,
University of Texas Medical Branch
August 11, 2020
“Polymorphism of Protein Aggregates in Alzheimer’s Disease and Related Dementias”
Andrew P. Lieberman
Professor
Director of Neuropathology
University of Michigan Medical School
August 18, 2020
“Polyglutamine-mediated proteotoxicity in SBMA"
August 25, 2020
“Specific viral RNA drives the SARS CoV-2 nucleocapsid to phase separate "
A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5’-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5’-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2.
Silvia Marchesan
Professor
Chemical & Pharmaceutical Sciences Department, University of Trieste
September 12, 2020
“Entry to peptide Wonderland through the rabbit-hole”
Aphrodite Kapurniotu
Professor
TUM School of Life Sciences,
Technical University of Munich (TUM)
September 19, 2020
“IAPP cross interactions: from discovery to exploitation"
Marc Diamond
Professor
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center
September 26, 2020
“New insights into tau prion propagation”
David Eisenberg
Professor
Department of Chemistry and Biochemistry and Biological Chemistry
University of California, Los Angeles
October 3, 2020
“Pathogenic vs Reversible Functional Amyloid"
Samrat Mukhopadhyay
Professor
Centre for Protein Science, Design & Engineering,
Indian Institute of Science Education and Research
October 10, 2020
"The Role of Intrinsic Disorder and Dynamics in Biological Phase Transitions "
Martin Muschol
Associate Professor & Graduate Director
Department of Physics
University of South Florida
October 17, 2020
“Distinct species of amyloid oligomers and their biological activities”
Jennifer Lee
Senior Investigator
Laboratory of Protein Conformation and Dynamics
NHLBI, NIH, USA
October 24, 2020
“The complex landscape of α-synuclein”
Markus Zweckstetter
Professor
German Center for Neurodegenerative Diseases (DZNE)
Max Planck Institute for Biophysical Chemistry
University Medical Centre Göttingen
October 31, 2020
“Molecular underpinnings of the life and death of Tau"
Birgit Strodel
Professor
Research Centre Jülich
Institute for Structural Biochemistry
November 7, 2020
“Computational studies on the effects of in vivo conditions on amyloid-β aggregation”
Cong Liu
Principal Investigator
Interdisciplinary Research Center on Biology & Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
November 14, 2020
“How chaperones regulate protein phase transition and its role in neurodegenerative disease”
Songi Han
Professor
Department of Chemistry & Biochemistry
Department of Chemical Engineering
University of California Santa Barbara
November 21, 2020
"Tracking the dynamic conformation ensemble of tau along its aggregation pathway"
Meytal Landau
Associate Professor
Department of Biology
Technion - Israel Institute of Technology
December 5, 2020
"Virulent and Antibacterial Fibrils in Infectious and Aggregation Diseases"
Christian Griesinger & Leif Antonchmidt
Professor (Dr. Christian Griesinger)
Researcher (Dr. Leif Antonchmidt)
Dept. of NMR based structural biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
December 12, 2020
"Interference with protein aggregation at the membrane: structural biology and therapy"
Vladimir Uversky
Professor
College of Medicine Molecular Medicine
University of South Florida
December 19, 2020
"From polyfunctionality to multipathogenicity with intrinsic disorder"
Elisar Barbar & Heather Forsythe
Professor (Dr. Elisar Barbar)
Graduate Student (Heather Forsythe)
Faculty Director of the Oregon State University Biomolecular NMR Facility, and Department Head
January 09, 2020
"Multivalency and protein disorder in virus protein interactions: Common themes among Rabies virus and SARS-CoV2"
Mei Hong
Professor
Department of Chemistry
Massachusetts Institute of Technology
January 16, 2021
"Molecular structures of glucagon and tau fibrils from NMR "
Elizabeth Rhoades
Associate Professor
Department of Chemistry
University of Pennsylvania
January 23, 2021
"Investigating the role of N-terminal acetylation on alpha-synuclein structure and function"
January 30, 2021
"Repeat associated non-AUG (RAN) translation in neurodegenerative disease: molecular insights and therapeutic opportunities"
February 06, 2021
"Metabolite Self-Assembly: Extension of the amyloid hypothesis"
Dieter Willbold
Professor
Institute of Complex Systems & Forschungszentrum Juelich GmbH
February 13, 2021
"Aβ oligomer disassembly into monomers is beneficial for cognition and memory in transgenic and non-transgenic Alzheimer animal models"
"Heterogeneity of Aβ Aggregates"
Yuji Sugita
Chief Scientist
RIKEN
February 27, 2021
"Replica-exchange simulations on the conformational dynamics of spike protein on the surface of SARS-CoV-2"
March 06, 2021
Alemayehu Gorfe
Associate Professor
University of Texas, Houston
"The intrinsically disordered membrane anchor of Ras proteins sorts membrane lipids"
"p53 amyloid formation associated with cancer"
March 20, 2021
John Straub
Professor, Boston University
"The roles of monomer and membrane in Aβ-protein genesis and aggregation"
Communications Biology volume 4, Article number: 120 (2021).
The thermodynamic hypothesis of protein folding, known as the “Anfinsen’s dogma” states that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, inconsistent with the Anfinsen’s dogma, globular proteins can misfold to form amyloid fibrils, which are ordered aggregates associated with diseases such as Alzheimer’s and Parkinson’s diseases. Here, we present a general concept for the link between folding and misfolding. We tested the accessibility of the amyloid state for various proteins upon heating and agitation. Many of them showed Anfinsen-like reversible unfolding upon heating, but formed amyloid fibrils upon agitation at high temperatures. We show that folding and amyloid formation are separated by the supersaturation barrier of a protein. Its breakdown is required to shift the protein to the amyloid pathway. Thus, the breakdown of supersaturation links the Anfinsen’s intramolecular folding universe and the intermolecular misfolding universe.
No ZOOMinar
on March 27th and April 3rd
Enjoy the break!
April 10, 2021
Sudipta Maiti
Tata Institute of Fundamental Research,
Mumbai 400005, INDIA
Email: maiti@tifr.res.in, URL: biophotonics.co.in
“Probing toxic protein oligomers: From test tubes to patient-derived neurons”
Understanding how amyloid aggregates actually become toxic is one of the challenges in developing a treatment for diseases such as Alzheimer’s and Parkinson’s. One of the major possibilities is that the small oligomeric aggregates incorporate into the cell membrane and make specific functional structures which ultimately cause toxicity. However, very little is known about the structure of the oligomers, the stoichiometry of the toxic oligomer, its insertion into the membrane, and subsequent cellular interactions. Perhaps the hardest problem is to establish the correlation of all these parameters with the actual disease. Here we address these issues for Amyloid-beta, which is associated with Alzheimer’s disease. Nature has provided some clues for Alzheimer’s in terms of the location of disease-accelerating mutations, correlations with other protein isoforms, and neuron-type specific vulnerabilities. However, they have been hard to interpret. Using tools such as nanosecond FCS, time resolved FRET, solid state NMR, membrane-mediated SERS, single molecule photobleaching, and Alzheimer’s patient-derived neurons, we are finally making sense of some of these clues.
References:
1) Dey et al., Chem. Eur. J., (2021), https://doi.org/10.1002/chem.202100328
2) Dey et al., Physical Chemistry Chemical Physics (2020) 22 (26), 14613
3) Chandra et al., Chemical Communications (2018) 54 (56), 7750-7753
4) Bhowmik et al., ACS Nano (2015), 9 (9), 9070-9077
5) Sarkar et al., Angewandte Chemie (2014) 126 (27), 6948-6948.
April 17, 2021
Sheena Radford
Professor
Structural Molecular Biology, Univ. of Leeds
"Seeing the molecular details of amyloid formation"
April 17, 2021
Sabine Ulamec
"A short motif in the N-terminal region of alpha-synuclein is critical for aggregation"
