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Dynamic Protocellular systems

Biology is well equipped in exploiting a large number of out of equilibrium processes to support life. A complete understanding of these mechanisms is still in its infancy due to the complexity and number of the individual components involved in the reactions. However, a bottom up approach allows us to replicate key biological processes using a small number of basic building blocks. This methodology has the added advantage that properties and characteristics of the artificial cell can be readily tuned and adapted. Working between biophysics, materials science and synthetic biology we reimagine and translate the physical phenemona which drive out of equilibrium processes in cells into novel, robust and dynamic systems for synthetic biology applications.

Compartmentalisation

A key property of the cell is its ability to compartmentalize chemical reactions. This allows the cell to control different chemical and physical environments, utilize the membrane as a reaction surface and protect enzymes and proteins from degradation. Membrane delineated compartments based on lipids have been extensively used to fulfill this criteria, however they lack an internal heterogeneity that is characteristic of natural cells. Therefore, membrane free droplets based on coacervation or liquid-liquid phase separation have not only been associated with mechanisms within the natural cell but have offered an alternative model to compartmentalization.

We use a range of techniques to understand the chemical and physical processes which drive molecular organization in lipids, polymers and proteins to rationally control self-assembly for the construction of novel proto-cellular platforms. This methodology is applied to protein-lipid and protein-polymer interactions as well as in-vitro compartmentalized transcription-translation processes which enables us to activate our compartments in a highly controlled manner. In addition, understanding these interactions can give insights to key questions in the origin of life i.e. what were the conditions required to drive molecular organization from disorder? and how did a biological world derive from chemistry?

Methodological and technical expertise:

  • Artificial cell synthesis (coacervates, lipid vesicles, hybrid protocells)
  • High pressure SAXS and CD for soft matter
  • Cell free expression
  • Analytical techniques (spectroscopy, DLS, DSC, ITC)
  • Lipid Membrane curvature (inverse bicontinuous cubic phases)
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