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Self-Perpetuating Structural States in Biology, Disease, and Genetics

Organized by Susan Lindquist and Steven Henikoff

March 22-24, 2002
Washington, DC

Meeting Overview
In recent years two previously separate and independently exciting fields have come to have a great deal in common. Both the transmission of phenotypes via the formation of protein amyloids and the inheritance of chromatin states involve self-perpetuating assemblies of proteins. There is evidence for some common structural features and conceptual frameworks, and these commonalities are likely to extend over a much broader range of phenomena. The goal of this meeting is to create new understandings from the standpoint of genetics and biophysics, and to foster new insights and interactions.

Differential states of gene expression are familiar to all biologists, because changes in activity states are fundamental to life processes. Although differential gene expression is becoming understood with increasing detail, the mechanisms that underlie the maintenance of these different expression states—either during development or from generation to generation—are largely obscure. When cells divide, gene expression states are transmitted to daughters, as revealed in the numerous examples of epigenetic phenomena in animals, plants, and fungi. Some epigenetic phenomena involve inheritance of chromatin structural states. For example, differential histone methylation appears to distinguish chromatin in cytologically different conformational states. Other epigenetic phenomena are maintained by protein-only mechanisms. For example, the yeast prion proteins form amyloid fibers in vitro and seed their own assembly in vivo and in vitro. At the same time, protein biochemists studying a group of human diseases, collectively known as the amyloid diseases, have made much progress in understanding how proteins can change conformational states and how proteins in one of those states can influence other proteins to adopt the same state.

This meeting will bring together people who have only recently realized how closely their systems interface with one another. They have a great deal to teach each other in terms of methodologies, experimental approaches and the underlying nature of the biological phenomena they are studying.

Day 1:

Sackler Lecture
Mad Cows Meet Psi-Chotic Yeast: New Paradigms in Genetics and Disease
Susan Lindquist

Morning Session: Self-Perpetuating Protein Conformations
Keynote Speaker: Charles Weissmann, Imperial College School of Medicine at St. Mary's
Propagation of Prions

The Yeast Prion [URE3] is a Heritable Amyloid of Ure2p: Genetics and Mechanisms
Reed Wickner, National Institutes of Health

Prion::Prion Interactions, Predisposing Factors
Susan Liebman, University of Illinois at Chicago

Self-Perpetuating Protein Conformations and Memory
Eric Kandel and Kausik Si, Columbia University

Afternoon Session: Protein Conformation Changes, Amyloid and Disease

Huntingtin Protein Assembly, Trafficking and Drug Interactions
Erich Wanker, Max-Delbruck Center for Molecular Medicine, Berlin

Drosophila Model for Neurodegenerative Disease, Protein::Protein Interactions
Nancy Bonini, University of Pennsylvania, Howard Hughes Medical Institute

Amyloid Disease Proteins and Chaperone Interactions
Ulrich Hartl, Max-Planck-Institute for Biochemistry, Martinsried

Links Between Protein Folding and Human Disease
Chris Dobson, University of Cambridge

Understanding the Energy Landscape Associated with Transthyretin Amyloid Diseases and Manipulating it to Prevent Amyloidosis
Jeffrey W. Kelly, The Scripps Research Institute

Day 2:

Morning Session: Chromatin Structural States

Insulation of Genes from Silencing Chromatin
Gary Felsenfeld, NIH

Epigenetic Control of Higher-order Chromatin Assembly
Shiv Grewal, Cold Spring Harbor Lab

Prion Diversity: Multiple Functions including Transcription States
Susan Lindquist, Whitehead Institute

The Challenge of Creating a Silent Chromatin State at Yeast Telomeres: Heritability and Promiscuity
Dan Gottschling, Fred Hutchinson Center

Connections Between Breast Cancer Metastasis and Gene Silencing from Sudies on Heterochromatin Protein 1 in Humans and Drosophila
Lori Wallrath, University of Iowa

Afternoon Session: Self-Perpetuating Genetic Interactions

Epigenetic Pili Switches in Bacteria
David Low, UC Santa Barbara

Replication-independent assembly of chromatin utilizes variant H3 histones
Steve Henikoff, Fred Hutchinson Center

Control of DNA Methylation: Lessons from Fungi
Eric Selker, U. of Oregon

Genetics of DNA methylation in Arabidopsis
Steve Jacobsen, UCLA

RNA-Based Epigenetic Silencing in Plants
Marjori Matzke, Austrian Academy of Sciences

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