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Intrinsically Disordered Proteins
Gordon Research Conference

Disordered Proteins: From Mechanisms to Therapeutic Opportunities

Dates

June 26 - July 1, 2016

Location

Les Diablerets Conference Center
Les Diablerets, Switzerland

Organizers

Chairs:
Richard W. Kriwacki & Monika Fuxreiter

Vice Chairs:
Vincent J. Hilser & Sonia Longhi

Meeting Description

This GRC will provide a broad overview of the intrinsically disordered proteins (IDP) field and also address the state-of-the-art in several vital, emerging areas. Cutting-edge themes regarding the roles of disordered proteins in both normal cells and disease will be discussed. Disordered proteins are involved in the pathology of numerous diseases, including cancer, neurodegenerative diseases, and infectious diseases (e.g., viral infections) and important discoveries have recently shown that small molecules can alter cellular behavior through interactions with disordered regions of proteins. Owing to the importance of these results in drug discovery, many lectures will address therapeutics- and disease-related themes.

The key scientific objectives of this conference are:

  • To address the molecular mechanisms of IDP function. While it is widely appreciated that a large fraction of human proteins exhibit disordered regions, in only a small fraction of cases are the mechanisms of their functions understood. Many lectures will endeavor to fill this knowledge gap. The conference will also address how the molecular mechanisms of disordered protein function are altered in disease.
  • To discuss therapeutic opportunities involving disordered proteins. While the concept of "drugging IDPs" was once considered heretical, there are now several published reports on small molecules that exert their biological effects through interactions with disordered and/or flexible regions of proteins. Several lectures will address innovative therapeutic approaches for targeting disordered proteins and/or their interaction partners, with speakers representing academic research groups as well as major pharmaceutical companies.
  • To address the role of disordered proteins in membrane-less organelles. Recent discoveries have shown that certain disordered proteins, either individually or together with RNA, weakly self-associate to cause phase separation into liquid-like or gel-like structures within membrane-less organelles. Little is known, however, about the molecular mechanisms of these assembly phenomena and how these assemblies contribute to biological functions. Furthermore, membrane-less organelles have been implicated in disease but the underlying molecular mechanisms are poorly understood. Several pioneers in this emerging field will present lectures at the conference.

We encourage participation in the conference by scientists already working in the disordered proteins field, cell biologists working on IDP-related molecular processes, and pharmacologists seeking new targets but also welcome others less familiar with the pervasive roles of IDPs in biology and disease. We especially encourage young scientists to attend this GRC, and the accompanying GRS, to learn about the scientific challenges and opportunities that await them.

Related Meeting

This GRC was held in conjunction with the "Intrinsically Disordered Proteins" Gordon Research Seminar (GRS). Refer to the associated GRS program page for more information.

Contributors

Final Meeting Program

Sunday
4:00 pm - 8:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKeynote Session: Emerging Themes; Disorder in Cellular Organization and as a Therapeutic Target
Discussion Leader: Sonia Longhi (CNRS / Aix-Marseille University, France)
7:40 pm - 7:50 pmOpening Remarks
7:50 pm - 8:20 pmMadan Babu (MRC Laboratory of Molecular Biology, United Kingdom)
"How Does Protein Disorder Enable Phenotypic Diversity?"
8:20 pm - 8:35 pmDiscussion
8:35 pm - 8:50 pmStefan Rudiger (Utrecht University, The Netherlands)
"IDR-Decorated Nano-Aggregates Derail Signalling"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:15 pmWolfgang Peti (Brown University, USA)
"IDPs in Cell Cycle and as Drug Targets"
9:15 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmExploring the Diversity of IDP Cellular Functions
Discussion Leader: Keith Dunker (Indiana University School of Medicine, USA)
9:00 am - 9:20 amJohn Bushweller (University of Virginia, USA)
"The AF9 Saga: Intrinsically Disordered Protein, Epigenetic Signaling, and Leukemia"
9:20 am - 9:35 amDiscussion
9:35 am - 9:50 amGian Tartaglia (Centre for Genomic Regulation (CRG), Spain)
"Structural Disorder and Aggregation of RNA-Binding Proteins"
9:50 am - 9:55 amDiscussion
9:55 am - 10:15 amJames Hurley (University of California, Berkeley, USA)
"Dynamics and Disorder in Autophagy"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:20 amHaribabu Arthanari (Harvard Medical School, USA)
"Deterring Structural Tendencies of Disordered Proteins by Inhibiting the Enabler"
11:20 am - 11:35 amDiscussion
11:35 am - 11:50 amIwo Koenig (University of Zurich, Switzerland)
"Single-Molecule Spectroscopy of Intrinsically Disordered Proteins in Live Eukaryotic Cells"
11:50 am - 11:55 amDiscussion
11:55 am - 12:15 pmMartha Cyert (Stanford University, USA)
"Putting It On and Taking It Off: Identifying Phosphatase Signaling Networks"
12:15 pm - 12:30 pmDiscussion
12:30 pmGroup Photo / Lunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmProtein Disorder Within Assemblies and Machines
Discussion Leader: Benjamin Schuler (University of Zurich, Switzerland)
6:00 pm - 6:20 pmSteven Hahn (Fred Hutchinson Cancer Research Center, USA)
"'Fuzzy' Complexes and Transcription Activation Mechanisms"
6:20 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmBernd Bukau (University of Heidelberg, Germany)
"Cellular Mechanisms Driving the Formation and Solubilization of Protein Aggregates"
6:55 pm - 7:10 pmDiscussion
7:10 pm - 7:25 pmFrauke Graeter (Heidelberg Institute for Theoretical Studies, Germany)
"Molecular High-Five: Fast Yet Specific Binding of IDPs to Their Partners"
7:25 pm - 7:30 pmDiscussion
7:30 pm - 7:50 pmMarkus Zweckstetter (German Center for Neurodegenerative Diseases, Germany)
"Intrinsically Disordered Proteins in Neurodegeneration"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Tuesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmMechanisms of Interactions Involving Disorder
Discussion Leader: Peter Tompa (Vlaams Instituut voor Biotechnologie, Belgium)
9:00 am - 9:20 amCharalampos Kalodimos (University of Minnesota, USA)
"Interaction of Unfolded Proteins with Molecular Chaperones"
9:20 am - 9:35 amDiscussion
9:35 am - 9:50 amKatherine Stott (University of Cambridge, United Kingdom)
"A Tale of Two Tails"
9:50 am - 9:55 amDiscussion
9:55 am - 10:15 amRachel Klevit (University of Washington, USA)
"Recognition of Disordered Substrates by a Disordered Enzyme: The Peculiar Case of Ubiquitin-Conjugating Enzyme Ube2w"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:20 amLouis Renault (I2BC, CNRS, France)
"Study of the Functional Versatility of Small Intrinsically Disordered Beta-Thymosin/WH2 Domains in the Regulation of Actin Cytoskeleton Dynamics"
11:20 am - 11:35 amDiscussion
11:35 am - 11:50 amAssaf Friedler (The Hebrew University of Jerusalem, Israel)
"The Interplay Between Structured and Disordered Domains"
11:50 am - 11:55 amDiscussion
11:55 am - 12:15 pmMaria Sunnerhagen (Linkoping University, Sweden)
"Disordered Complexes of the Oncoprotein Myc Transactivation Domain"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmThe Diverse Biology of Disordered Proteins
Discussion Leader: Madan Babu (MRC Laboratory of Molecular Biology, United Kingdom)
6:00 pm - 6:20 pmAnthony Hyman (Max Planck Institute of Cell Biology and Genetics, Germany)
"Aberrant Phase Transitions and Disease"
6:20 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmNorman Davey (University College Dublin, Ireland)
"Short Linear Motifs - The Unexplored Frontier of the Eukaryotic Proteome"
6:55 pm - 7:10 pmDiscussion
7:10 pm - 7:25 pmFrancois-Xavier Theillet (CNRS - Institute of Integrative Biology of the Cell (I2BC), Université Paris-Saclay, France)
"Multisite, Gradual Phosphorylation of the Transcription Factor Elk1 Promotes Recruitment and Later Release of the Transcription Machinery"
7:25 pm - 7:30 pmDiscussion
7:30 pm - 7:50 pmLila Gierasch (University of Massachusetts Amherst, USA)
"IDPs and Protein Homeostasis: Balancing Order and Disorder"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmRoles of IDPs in Membrane-Less Organelles; Form and Function
Discussion Leader: Rohit Pappu (Washington University in St. Louis, USA)
9:00 am - 9:20 amJulie Forman-Kay (Hospital for Sick Children, Canada)
"NMR- and Sequence-Derived Insights into Phase-Separated States of IDPs"
9:20 am - 9:35 amDiscussion
9:35 am - 9:50 amIvan De Curtis (San Raffaele University and San Raffaele Scientific Institute, Italy)
"A Molecular Network Regulating Cell Edge Dynamics During Migration"
9:50 am - 9:55 amDiscussion
9:55 am - 10:15 amSteve McKnight (University of Texas Southwestern Medical Center, USA)
"Cross-Beta Polymerization of Low Complexity Domains Involved in Information Transfer from Gene to Message to Protein"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:20 amGeraldine Seydoux (John Hopkins University School of Medicine, USA)
"Regulation of RNA Granule Assembly by Intrinsically Disordered Proteins"
11:20 am - 11:35 amDiscussion
11:35 am - 11:50 amNicolas Fawzi (Brown University, USA)
"Atomic Details of RNA-Binding Protein Phase Separation Mediated by Low Complexity Domains"
11:50 am - 11:55 amDiscussion
11:55 am - 12:15 pmJ. Paul Taylor (St. Jude Children's Research Hospital, USA)
"Dynamic RNA-Protein Assemblies in Neurological Disease"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmEnsemble Representations of IDPs; Methods and Links with Function
Discussion Leader: Martin Blackledge (Institute for Structural Biology, CNRS, France)
6:00 pm - 6:20 pmToshio Ando (Kanazawa University, Japan)
"Watching the Structure, Function and Dysfunction of IDPs by High-Speed AFM"
6:20 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmRobert Konrat (University of Vienna, Austria)
"Finding Order in Disordered Proteins"
6:55 pm - 7:10 pmDiscussion
7:10 pm - 7:25 pmPerdita Barran (University of Manchester, United Kingdom)
"Framing Disorder: The Use of Ion Mobility Mass Spectrometry to Provide Snapshots of Disordered Conformations"
7:25 pm - 7:30 pmDiscussion
7:30 pm - 7:50 pmClaudio Luchinat (University of Florence, Italy)
"Monitoring the Conformational Space Available to IDPs"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Thursday
7:30 am - 8:30 amBreakfast
8:30 am - 9:00 amBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
9:00 am - 12:30 pmTherapeutic Strategies Involving IDPs
Discussion Leader: Wolfgang Peti (Brown University, USA)
9:00 am - 9:20 amKurt Deshayes (Reflexion Pharmaceuticals, USA)
"The Development of 'Mirror Image' Proteins as Therapeutics"
9:20 am - 9:35 amDiscussion
9:35 am - 9:50 amChristopher Macraild (Monash Institute of Pharmaceutical Sciences, Australia)
"The Antibody Interactions of Intrinsically Disordered Proteins: Towards a Malaria Vaccine Based on Disordered Antigens"
9:50 am - 9:55 amDiscussion
9:55 am - 10:15 amJonathan Moore (Vertex Pharmaceuticals Inc., USA)
"Discovery of Small Molecule Inhibitors of IDP Complexes in Cancer"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:20 amJeffrey Toretsky (Georgetown University, USA)
"Small Molecule Targeting of the Intrinsically Disordered Oncoprotein EWS-FLI1"
11:20 am - 11:35 amDiscussion
11:35 am - 11:50 amGabriella Heller (University of Cambridge, United Kingdom)
"Targeting Disordered Proteins with Small Molecules Using Entropy"
11:50 am - 11:55 amDiscussion
11:55 am - 12:15 pmMark Hochstrasser (Yale University, USA)
"Intrinsically Disordered Proteins in the Ordered Assembly of the Proteasome Complex"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmKeynote Session: Disorder in Protein Aggregation and Inheritance; Future Directions of IDP Research
Discussion Leader: Vincent Hilser (Johns Hopkins University, USA)
6:00 pm - 6:30 pmGary Daughdrill (University of South Florida, USA)
"Precise Levels of Transient Helicity Are Required for IDP Function"
6:30 pm - 6:45 pmDiscussion
6:45 pm - 7:00 pmDaniel Jarosz (Stanford University, USA)
"Intrinsically Disordered Proteins Drive Heritable Transformations of Biological Traits"
7:00 pm - 7:10 pmDiscussion
7:10 pm - 7:30 pmSteven Finkbeiner (University of California, San Francisco, USA)
"Translating Insights About IDPs and Neurodegenerative Disease into Therapeutic Strategies"
7:30 pm - 7:45 pmDiscussion
7:45 pm - 8:00 pmClosing Remarks
8:00 pmDinner
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R13CA203288. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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