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Cliff Brangwynne
The document discusses the role of liquid-liquid phase transitions in the organization of intracellular components and their implications for diseases such as Alzheimer's and ALS. It highlights various studies related to membrane-less organelles and the aggregation of disordered proteins. The research emphasizes the connection between intracellular dynamics, genetic information flow, and pathological conditions.
Cliff Brangwynne
- 1. Intracellular Phase Transitions FromOrganelle Function to Disease Cliff Brangwynne Princeton University Soft Living Matter Group Alzforum Webinar, October 30, 2015
- 2. Germ (P) granules Processingbodies Nucleoli RNA/Protein (RNP) Bodies Membrane-less organelles Spector, Parker, Strome, Misteli, Lamond et.al.
- 3. 3 Pathological Protein Aggregation Text Alzheimers Madcow disease Amyotrophic Lateral Sclerosis (ALS) 2 per 100,000 1 in 9 Americans over 65 quite rare (170 deaths worldwide in 10 years)
- 4. Elbaum, CPB et.al.PNAS 2015 Zhang, CPB, Gladfelter, et.al. Mol.Cell. 2015 Berry, Weber, Haataja, CPB et.al. PNAS 2015 Weber and CPB, Curr. Biol. 2015 Berry, CPB et.al. PNAS 2015 Disordered Proteins (IDP/LCS) CPB, Hyman, et.al. Science 2009 Lee, CPB, et.al. Phys.Rev.Lett 2013 P Granules Liquid-liquid phase transitions appear to be a ubiquitous mechanism for intracellular organization Nucleoli Synthetic Bodies Nott, Forman-Kay, Baldwin et.al. Molecular Cell 2015Li, Rosen et.al. Nature 2012 Multi-valent Proteins DDX4 Nuclear Bodies CPB et.al. PNAS 2011 Feric and CPB Nature Cell Bio. 2013
- 5. Physiological Liquids andPathological Solids Zhang, CPB, Gladfelter et.al. Molecular Cell, 2015 Whi3 Patel, Lee, Hyman, Alberti Cell 2015 FUS Molliex, Mittag, Taylor et.al. Cell 2015 Lin, Protter, Rosen, Parker Molecular Cell, 2015 hnRNPA1 Weber & CPB Cell 2012
- 6. RNA Impacts DropletAssembly and Properties Laf-1 Elbaum-Garfinkle, Kim, Szczepaniak, Eckmann, Myong, CPB PNAS 2015 Nucleoli Nucleoli in HeLa cells Intergenic spacer 18s 5.8s 26s ITS1 ITS2nascent rRNA transcript Tandem rDNA gene repeats Nucleolus Intergenic spacer Internal Transcribed Spacers Ribosomal subunits Zhang, CPB, Gladfelter et.al., Mol. Cell 2015 Berry, Weber, Vaidya, Haataja, CPB, PNAS 2015 Whi-3
- 7. DNA RNA Protein PhaseTransitions and the Flow of Genetic Information
- 8. www.softlivingmatter.comSoft Living Matter Group Funding Collaborators BrangwynneLab Students & Postdocs Shani Elbaum Nilesh Vaidya Sravanti Uppaluri Steven Wei Yongdae Shin Carlos Chen Lian Zhu Nicole Taylor Marina Feric Aleena Patel Laura Gray Mikko Haataja (Princeton) Joel Berry (Princeton) Howard Stone (Princeton) Amy Gladfelter (Dartmouth) Richard Kriwacki (St. Jude) Rohit Pappu (WUSTL) Christian Eckmann (Halle) Sua Myong (UIUC) Huaiying Zhang Steph Weber