Molecular Bases of Proteinopathies

2020-2021 virtual meeting of talks, activities, and discussion on "protein multimerization: the bad and the good"

The goal of this event is to bring scientific leaders working in the field of 'Amyloid Research' together from across the globe

Registration required to secure a zoom link (Registration)

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) from 10:00 AM to ~11:00 AM (EDT). This virtual seminar includes a ~35 minutes presentation and ~15 minutes for questions and answers. We expect that there will be about 450 to 500 researchers participating from all over the world. The virtual presentations will be recorded and made available in a YouTube channel.


Ayyalusamy (Rams) Ramamoorthy, Biophysics and Chemistry, University of Michigan


Joan Shea, Chemistry and Biochemistry & Physics, University of California Santa Barbara


Magda Ivanova, Department of Neurology, University of Michigan


Bikash R. Sahoo, Biophysics and Chemistry, University of Michigan


*For general inquiry please write us at


The invited lectures on Proteinopathies will take place via Zoom from 10:00 - 11:30 AM (EST) on Tuesdays in August (and shifted to Saturdays from September). After a brief introduction of the speaker by a moderator (~2 minutes), the invited speaker will present the lecture for 30-35 minutes followed by a question-and-answer session led by the moderator (for ~10 minutes). Lectures will be recorded to allow off-line viewing, but recording will be turned off at the speaker's preference. To facilitate the question-and-answer session, the audience will be invited to submit questions during the lecture using the Q&A folder in Zoom. After the lecture, the moderator will read the questions to the speaker (or a subset of related questions) and if needed unmute a participant for follow-up discussion. Depending on the availability of the speaker, informal discussion may continue for ~20 minutes after the formal session.

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


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


Director of Neuropathology

University of Michigan Medical School

August 18, 2020

Polyglutamine-mediated proteotoxicity in SBMA"

Amy Gladfelter


Department of Biology

University of North Carolina

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


Chemical & Pharmaceutical Sciences Department, University of Trieste

September 12, 2020

“Entry to peptide Wonderland through the rabbit-hole”

Aphrodite Kapurniotu


TUM School of Life Sciences,

Technical University of Munich (TUM)

September 19, 2020

“IAPP cross interactions: from discovery to exploitation"

Marc Diamond


Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center

September 26, 2020

New insights into tau prion propagation

David Eisenberg


Department of Chemistry and Biochemistry and Biological Chemistry

University of California, Los Angeles

October 3, 2020

Pathogenic vs Reversible Functional Amyloid"

Samrat Mukhopadhyay


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


October 24, 2020

The complex landscape of α-synuclein

Markus Zweckstetter


German Center for Neurodegenerative Diseases (DZNE)

Max Planck Institute for Biophysical Chemistry

University Medical Centre Göttingen

October 31, 2020


Birgit Strodel


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


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


Gal Bitan


Department of Neurology

David Geffen School of Medicine, UCLA

December 12, 2020


Mei Hong


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

"TBU "

Laura P.W. Ranum

Director of Center for NeuroGenetics

University of Florida


January 30, 2021

"TBU "

Ehud Gazit


Tel Aviv University

February 06, 2021

"TBU "

Dieter Willbold


Institute of Complex Systems

Forschungszentrum Juelich GmbH

February 13, 2021

"TBU "

Mi Hee Lim


Korea Advanced Institute of Science and Technology (KAIST)

February 20, 2021

"TBU "

Alemayehu Gorfe

Associate Professor

University of Texas McGovern Medical School-Houston

March 06, 2021

"TBU "

Samir Maji


Department of Biosciences and Bioengineering,

Indian Institute of Technology, Bombay

March 13, 2021

"p53 amyloid formation associated with cancer"

Sheena Radford


Astbury Centre for Structural Molecular Biology, University of Leeds

April 17, 2021

"Seeing the molecular details of amyloid formation"

Omar El-Agnaf

Executive Director

Qatar Biomedical Research Institute QBRI

Joint Professor

College of Health and Life Sciences

April 24, 2021

“Role of α-synuclein phosphorylation at serine 129 in the pathogenesis of synucleinopathies: an active debate"

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are human neurodegenerative diseases characterized neuropathologically by the presence of neuronal α-synuclein inclusions, named as Lewy bodies and Lewy neurites. Increasing number of studies highlighted the aberrant accumulation of phosphorylated α-synuclein at the residue Serine129 (pS129) in the brain of PD and DLB patients, suggesting that phosphorylation may play a vital role in the regulation of α-synuclein aggregation and subsequent neuronal degeneration. However, a comprehensive understating of the exact role of α-synuclein phosphorylation at S129 is still lacking. Here, we study the time-point at which pS129 modification occurs in the process of α-synuclein aggregation and its role in initiation, progression and cellular toxicity of the disease. Therefore, with the collaboration of many international teams we have addressed this issue by designing and executing important in vitro, ex vivo, and in vivo experiments using various models, in addition to post-mortem human brain studies. Contrary to the putative view of pS129-α-synuclein being particularly disease-relevant form of α-synuclein, we suggest that pS129 diminished aggregation-propensity, attenuated cytotoxicity, and occurs subsequent to initial α-synuclein aggregation. Our novel findings have important implications for the design of future neuropathological studies and the development of therapeutic approaches targeting of distinct α-synuclein species.