Choosing a research topic is an important decision at any level. The choice shapes decisions about what graduate lab to join, which post-doctoral position to pursue, how to start an independent lab, and what companies might make good employers. The thing to remember is that “the choice” can, and perhaps should, be made many times during a career, and each time, it can take an exciting new turn. Lara Szewczak sat down with Amy Gladfelter and Tony Hyman to talk about what it takes for a researcher to pivot—to decide that they want to embark on a new line of research. What does it mean at different points in a career, and how can you motivate colleagues to follow?

that’s where the pivot begins—is the mystery. I think the pace and the pressure to produce—the sense that you need to be in the thing that is getting published right now—is covering up a lot of the mystery.You need mentors to say, ‘No, this is how you will actually get grants. This is how you’ll get recognized by something a bit different.’

Read the interview of Amy Gladfelter and Tony!

Zoltan’s paper is out!

Former postdoc Zoltan worked with the Whelan lab on VSV (Vesicular Stomatitis Virus). RNA viruses like VSV compartmentalize their replication machinery to evade detection by the host. However, it has been unclear how the virus can concentrate the machinery for RNA synthesis. Now it is shown that the replication compartments have liquid like properties and form by phase separation. Liquid-liquid phase separation (LLPS) seems to play an important role in host-pathogen interactions.

[KGVID]https://hymanlab.mpi-cbg.de/hyman_lab/wp-content/uploads/2018/09/vsv-eGFP.mov[/KGVID]

Dynamics of VSV inclusions

Phase Transitions Drive the Formation of Vesicular Stomatitis Virus Replication Compartments. Heinrich BS, Maliga Z, Stein DA, Hyman AA, Whelan SPJ. MBio. 2018 Sep 4;9(5). pii: e02290-17. doi: 10.1128/mBio.02290-17.

Congratulations to Richard! Check out his website

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.

Highlights

• 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.

reference: https://doi.org/10.1016/j.jmb.2018.06.038.

go to the pdf

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

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

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!