Engineering Cellular
Compartments

  • Structure, dynamics and adaptation of membraneless organelles (MLOs) in bacteria
  • Spatiotemporal modeling of MLOs
  • Engineering synthetic MLOs in eukaryotic cells
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Research overview

We study the biology of membraneless organelles (MLOs) in bacteria and use these findings to engineer synthetic MLOs in higher order organisms. 

Biomolecular condensate formation by phase separation has emerged as a new principle to explain the dynamic organization of living cells. We have uncovered an essential bacterial MLO, defined by liquid-liquid phase separation of the disordered protein PopZ, that is conserved across the extremely diverse and abundant α-proteobacteria.

  • Our lab is studying the structure, dynamics, and function of PopZ phase separation in the context of adaptation to environmental challenges.
  • We use this knowledge to engineer synthetic MLOs for interrogating properties and function of phase separation in human cell lines, as well as for therapeutic application

Selected Publications

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Significance

Biochemical processes within the cell take place in an environment that is highly crowded and heterogeneous. As a solution to this challenge, biomolecular condensation through liquid-liquid phase separation has been recognized recently as one way in which biomolecules spontaneously assemble or disassemble based on their chemical and physical properties and their surroundings.

Developing biomolecular systems with programmable phase behavior and composition is a promising new strategy for engineering spatial and temporal chemical reactions for cellular adaptation and therapeutics.

Selective sequestration of signalling proteins in a MLO reinforces the spatial regulation of asymmetry in Caulobacter

Selective recruitment and concentration of signalling proteins within membraneless compartments is a ubiquitous mechanism for subcellular organization

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caulobacter-polar-microdomain

Integrative visualization of the molecular structure of a cellular microdomain

 

 

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A modular platform for engineering function of natural and synthetic biomolecular condensates

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Technologies

We use high resolution imaging techniques and integrated modeling approaches to study the structure and dynamics of MLOs inside bacterial cells. Furthermore, we apply genetics and cell biology approaches to engineering bacteria-derived MLOs within mammalian cells.

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