Former postdoc Richard opens his own lab in Oxford

Congratulations to Richard! Check out his website

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We are organizing an EMBO Practical Course for studying phase separation in biology!

The course takes place 05 – 13 February 2019 in Dresden at the MPI-CBG,

register until 1st Oct. 2018, we are looking forward to seeing you here!


#EMBOphaseseparation / facebook


About the Practical Course

The field of cell biology is in the midst of a revolution in the understanding of how cells are biochemically organized. In recent years, research has shown that liquid-liquid phase separation is a critical organizing principle for cells, improper regulation of which can lead to dysfunction and disease. There are many exciting open research questions in this field, and we aim to provide students with an essential toolkit for addressing them. This course will provide high quality instruction in the physical chemistry theories underlying biological phase separation, followed by hands on practical training in the assays and cutting-edge techniques used in this emerging field. Dresden is a hub for phase separation research, and in addition to our local experts in biophysics and cell biology, our speakers and instructors will also include global authorities on these topics. Following the course, participants should be able to apply their newly learned techniques to their own projects and research questions. We hope that this course will establish the best practices in the field of biological phase separation, which the students can spread more widely at their home and future institutions.


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Jie’s paper on the molecular grammar of phase separation is out!

Our latest publication is out now in Cell! Congratulations to Jie and all the co-workers.


In this work, Jie Wang and colleagues worked with a family of prion like proteins (FUS family proteins) and suggest rules that define their phase separation behavior. In cells, FUS family proteins can phase separate into liquid like organelles. However, they can form as well aggregates that are linked to neurodegenerative diseases like ALS. Understanding and predicting their phase behavior will lead to a better understanding of their cellular functions.


For a scientific summary of his work and the original publication see below. Click here for a more general summary.


Fig. Hierarchical organization that gives rise to formation of condensates depicted here as spherical droplets


  • Phase separation of FUS requires both the N-terminal PLD and the C-terminal RBD
  • Tyrosine and arginine govern the saturation concentration of phase separation
  • Glycine maintains liquidity, whereas glutamine and serine promote hardening
  • An associative polymer model predicts the phase behavior of FUS family proteins


Fig. The number of arginines and tyrosines determine the phase behavior of FUS family proteins



Proteins such as FUS phase separate to form liquid-like condensates that can harden into less dynamic structures. However, how these properties emerge from the collective interactions of many amino acids remains largely unknown. Here, we use extensive mutagenesis to identify a sequence-encoded molecular grammar underlying the driving forces of phase separation of proteins in the FUS family and test aspects of this grammar in cells. Phase separation is primarily governed by multivalent interactions among tyrosine residues from prion-like domains and arginine residues from RNA-binding domains, which are modulated by negatively charged residues. Glycine residues enhance the fluidity, whereas glutamine and serine residues promote hardening. We develop a model to show that the measured saturation concentrations of phase separation are inversely proportional to the product of the numbers of arginine and tyrosine residues. These results suggest it is possible to predict phase-separation properties based on amino acid sequences.


Original Publication

J. Wang, J.M. Choi, A.S. Holehouse, X. Zhang, M. Jahnel, R. Lemaitre, S. Maharana, A. Pozniakovsky, D. Drechsel, I. Poser, R.V. Pappu, S. Alberti, A.A. Hyman: A molecular grammar underlying the driving forces for phase separation of prion-like RNA binding proteins. Cell, In Press (2018)

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Check out our new user’s guide for phase separation assays with purified proteins!


  • Membrane-less organelles form by phase separation
  • Membrane-less organelles can be reconstituted from minimal components
  • Phase-separating proteins are difficult to purify and handle
  • We provide guidelines and protocols for working with phase-separating proteins

The formation of membrane-less organelles and compartments by protein phase separation is an important way in which cells organize their cytoplasm and nucleoplasm. In vitro phase separation assays with purified proteins have become the standard way to investigate proteins that form membrane-less compartments. By now, various proteins have been purified and tested for their ability to phase separate and form liquid condensates in vitro. However, phase-separating proteins are often aggregation-prone and difficult to purify and handle. As a consequence, the results from phase separation assays often differ between labs and are not easily reproduced. Thus, there is an urgent need for high quality proteins, standardized procedures, and generally agreed upon practices for protein purification and conducting phase separation assays. This paper provides protocols for protein purification and guides the user through the practicalities of in vitro protein phase separation assays, including best-practice approaches and pitfalls to avoid. We believe that this compendium of protocols and practices will provide a useful resource for scientists studying the phase behavior of proteins.


go to the pdf

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Buffering disease: How the nucleus keeps proteins in check

High RNA concentration maintains RNA-binding proteins in solution and prevents pathological aggregates




Many age-related diseases affect the nervous system. One prominent example of a neurodegenerative disease is Amyotrophic Lateral Sclerosis (ALS). The brain tissue of ALS patients typically shows aggregates of so-called prion-like RNA-binding proteins. In the nucleus, these RNA-binding proteins are floating in solution, but when they are located outside of the nucleus, in the cytoplasm, they often form solid pathological aggregates. Researchers from the lab of Simon Alberti and Tony Hyman at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden wanted to investigate why these proteins never aggregate in the nucleus and what keeps them soluble there? Uncovering this mechanism may help to dissolve pathological aggregates in the cytoplasm…read more


Shovamayee Maharana, Jie Wang, Dimitrios K. Papadopoulos, Doris Richter, Andrey Pozniakovsky, Ina Poser, Marc Bickle, Sandra Rizk, Jordina Guillén-Boixet, Titus Franzmann, Marcus Jahnel, Lara Marrone, Young-Tae Chang, Jared Sterneckert, Pavel Tomancak, Anthony A. Hyman, Simon Alberti: RNA buffers the phase separation behavior of prion-like RNA binding proteins, Science, 12 Apr 2018

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Richard’s review on controlling non-membrane-bound organelles is out

Richard stayed in the lab just about a year but his contributions to the Science of the Hyman lab, not forgetting his many social contributions, have been quite big! Now he wrote a review with Tony for the Philosophical Transactions B on controlling non-membrane-bound organelles. They discuss energetically favourable interactions that could drive condensation, and on the basis of that, make qualitative predictions about how cells may control compartmentalization by condensates.

Controlling compartmentalization by non-membrane-bound organelles. Wheeler RJ, Hyman AA. Philos Trans R Soc Lond B Biol Sci. 2018 May 26;373(1747). pii: 20170193. doi: 10.1098/rstb.2017.0193. Review. PMID:29632271

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Edgar is giving a talk at the CSHL meeting Protein Homeostasis in Health and Disease

The Cold Spring Harbor meeting on Protein Homeostasis is taking place from April 17th-21th and Edgar will speak about how Molecular chaperones control the physical state of membrane-less compartments. Go Edgar!

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Congratulations to Stephanie for her successful collaboration with the Zerial lab!

Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria.

Hsu F, Spannl S, Ferguson C, Hyman AA, Parton RG, Zerial M.

Elife. 2018 Feb 22;7. pii: e32282. doi: 10.7554/eLife.32282


Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. Thus, it is fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosomal contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to mitochondria upon oxidative stress. This process is reversible and accompanied by an increase in Rab5-positive endosomes in contact with mitochondria. Interestingly, activation of Rab5 on mitochondria depends on the Rab5-GEF ALS2/Alsin, encoded by a gene mutated in amyotrophic lateral sclerosis (ALS). Alsin-deficient human induced pluripotent stem cell-derived spinal motor neurons are defective in relocating Rab5 to mitochondria and display increased susceptibility to oxidative stress. These findings define a novel pathway whereby Alsin catalyzes the assembly of the Rab5 endocytic machinery on mitochondria. Defects in stress-sensing by endosomes could be crucial for mitochondrial quality control during the onset of ALS.


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Congratulations to Sina and Adam for their fellowships!

Sina and Adam received both each an EMBO postdoc fellowship as well as a Marie Curie postdoc fellowship. This is a great success for both of them but as well for the lab. And yes, of course we celebrated it…

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ASAPbio cenference: Transparency, Recognition, and Innovation in Peer Review in the Life Sciences

Tony will be part of the ASAPbio conference on Transparency, Recognition and Innovation in Peer Review in the Life Sciences taking place February 7th to 9th at the HHMI headquarters in Chevy Chase, Maryland. Several aspects of peer review will be discussed in the meeting and importantly, you can follow the conference by live video streaming.

Check out two essays Tony wrote on Peer Feedback and the defence of the Peer review


ASAPbio (Accelerating Science and Publication in biology) is a scientist-driven initiative to promote the productive use of preprints in the life sciences.

Board of Directors
Ron Vale (President)
Cynthia Wolberger (Vice President)
James Fraser (Secretary & Treasurer)
Prachee Avasthi
Daniel Colón-Ramos
Tony Hyman
Heather Joseph
Harlan Krumholz
Maria Leptin
Harold Varmus
Dick Wilder (non-voting)

Jessica Polka

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  • News Archive

  • Selected Videos

    iBio video about P granule formation

    An interview with Tony about Phase Transitions and Disease

    Phase separation in cell polarity: Saha et al, Cell 2016

    Encouraging Innovation,

    The genetics linking temperature and fertility in worms: Leaver et al, Biology Open 2016

    Cell PaperFlick on Phase Transitions in Disease

    Check out this playlist to watch all the videos in our "Two Minute Talk" Series

    Ways of Growing, a film created for the MitoSys Project

    What is a Discovery?

    Embryonic Development of C.elegans