Research Description

The Regulation of Signal Transduction by Phase Separated Biomolecular Condensates

Research in my lab focuses on understanding the biophysical mechanisms and functional consequences of biological phase separation in neuronal and immunological signal transduction. Phase separation has emerged as a key mechanism that regulates cellular organization. Biomolecular condensates, or ‘membrane-less organelles’, concentrate specific proteins, nucleic acids, and small molecules without an encapsulating membrane. I have previously demonstrated the role that phase separation plays in regulating signal transduction, local actin rearrangement, and membrane cluster organization in studies that are published in Science and ELife. We use a combination of biophysical analysis, biochemical reconstitution, and cell biology to understand how the composition of biomolecular condensates dictates the function of the condensate. We are interested in understanding how the emergent biophysical properties of membrane associated phase separated condensates regulate membrane receptor organization and signal transduction in neurons and immune cells. In neurons, we are studying the role that the postsynaptic density plays in local actin polymerization, ion flux through membranes, and local RNA translation as well as understanding how the intrinsic biophysical properties of condensates determine the ability of condensates to associate with or repel other condensates on membranes. In immune cells, we are studying the role that phase separation of both lipids and proteins plays in regulating cell signaling and membrane associated signaling cluster organization. 

Publications

View all publications on PubMed

A composition-dependent molecular clutch between T cell signaling clusters and actin
Ditlev, J.A.*, Vega, A. R.*, Köster, D.V.*, Su, X., Lakoduk, A.M., Vale, R.D., Mayor, S., Jaqaman, K., Rosen, M.K.
ELife. 2019; 8:e42695  Read

Regulation of transmembrane signaling by phase separation
Case, L.B.§, Ditlev, J.A.§, Rosen, M.K.§
Annu Rev Biophys. 2019; 48: 465-494  Read

Stoichiometry controls activity of phase separated clusters of actin signaling proteins
Case, L.B., Zhang, X., Ditlev, J.A., Rosen, M.K.
Science. 2019 Mar 8; 363(6431): 1093-1097  Read

Who’s in and who’s out – Compositional control of biomolecular condensates
Ditlev, J.A.§, Case, L.B.§, Rosen, M.K.§
J. Mol. Biol. 2018 Nov 2; 430(23): 4666-4684  Read

Allosteric modulation of Grb2 recruitment to the intrinsically unstructured scaffold protein, LAT, by remote site phosphorylation
Huang, W.Y.C*, Ditlev, J.A.*, Chiang, H.-K., Rosen, M.K., Groves, J.T.
J Am Chem Soc. 2017 Nov 28; 139 (49): 18009-18015  Read

Reconstitution of TCR signaling using supported lipid bilayers
Su, X., Ditlev, J.A., Rosen, M.K., Vale, R.D.
Methods Mol Biol. 2017;1584:65-76  Read

Phase separation of signaling molecules promotes T cell receptor signal transduction
Su, X.*, Ditlev, J.A.*, Hui, E., Xing, W., Banjade, S., Okrut, J., King, D.S., Taunton, J., Rosen, M.K., Vale, R.D.
Science. 2016 Apr 29; 352(6285): 595-9  Read

There is more than one way to model and elephant. Experiment-driven modeling of the actin cytoskeleton
Ditlev J.A., Mayer B.J., Loew L.M.
Biophys J. 2013 Feb 5; 104(3): 520-32  Read

Stoichiometry of Nck-dependent actin polymerization in living cells
Ditlev J.A., Michalski P.J., Huber G., Rivera G.M., Mohler W.A., Loew L.M., Mayer B.J.
J. Cell Biol. 2012 May 21; 197(5): 643-658  Read

An open model of actin dendritic nucleation
Ditlev J.A., Vacanti N.M., Novak I.L., Loew L.M.
Biophys J. 2009 May 6; 96(6): 3529-3542  Read