cliff brangwynne

8
Intracellular Phase Transitions From Organelle Function to Disease Cliff Brangwynne Princeton University Soft Living Matter Group Alzforum Webinar, October 30, 2015

Upload: alzforum

Post on 13-Feb-2017

4.688 views

Category:

Science


0 download

TRANSCRIPT

Page 1: Cliff Brangwynne

Intracellular Phase Transitions From Organelle Function to Disease

Cliff Brangwynne

Princeton University

Soft Living Matter Group

Alzforum Webinar, October 30, 2015

Page 2: Cliff Brangwynne

Germ (P) granules

Processing bodies

Nucleoli

RNA/Protein (RNP) Bodies Membrane-less organelles

Spector, Parker, Strome, Misteli, Lamond et.al.

Page 3: Cliff Brangwynne

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)

Page 4: Cliff Brangwynne

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

Page 5: Cliff Brangwynne

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

Page 6: Cliff Brangwynne

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

Page 7: Cliff Brangwynne

DNA RNA Protein

Phase Transitions and the Flow of Genetic Information

Page 8: Cliff Brangwynne

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