cliff brangwynne
Post on 13-Feb-2017
4.693 Views
Preview:
TRANSCRIPT
Intracellular Phase Transitions From Organelle Function to Disease
Cliff Brangwynne
Princeton University
Soft Living Matter Group
Alzforum Webinar, October 30, 2015
Germ (P) granules
Processing bodies
Nucleoli
RNA/Protein (RNP) Bodies Membrane-less organelles
Spector, Parker, Strome, Misteli, Lamond et.al.
3
Pathological Protein Aggregation
TextAlzheimers
Mad cow disease
Amyotrophic Lateral Sclerosis (ALS)
2 per 100,000
1 in 9 Americans over 65
quite rare (170 deaths worldwide in 10 years)
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
Physiological Liquids and Pathological 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
RNA Impacts Droplet Assembly 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
DNA RNA Protein
Phase Transitions and the Flow of Genetic Information
www.softlivingmatter.comSoft Living Matter Group
Funding
Collaborators
Brangwynne Lab 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
top related