Artificial cellular counterparts (protocells) can be fabricated to produce explicit biomimetic outcomes such as RNA-mediated replication, gene expression, metabolism, etc. These synthetic mimics with cell-like traits, aim to answer fundamental questions regarding origin of cellularity from non-living components. However, minimal levels of structural/organisational complexity exhibited in current protocell designs, limits their application potential. The aim of this proposal is to use bottom-up approaches to precisely design and construct complex protocells through membrane coupled appendages and produce interactive protocellular communities which will recognize, sort and processes chemical signals through collective behaviour. The self-assembled protocellular colonies will be sequestered with complex enzymatic reaction networks which operate spontaneously and synergistically reminiscent to living cells. Several important functions such as selective formation of protocellular consortia, mimicking important biological functions such as IDH-kinase/phosphatase (AceK) circuitry from the Krebs cycle, redox-homeostasis, self-protection from chemical degradation will increase the complexity of the protocellular constructs producing the first example of functional proto-colonies. The expertise of the applicant in the field of organic synthesis, supramolecular chemistry and out-of-equilibrium self-assembly will be employed by the multidisciplinary and evolving field of protocells pioneered by the hosting group of Professor Stephen Mann FRS at the University of Bristol. The combined research efforts of the applicant and the Mann group will result in the successful realization of programmable protocells resulting in active self-assembling protocellular constructs and build their advanced forms capable of spatio-temporal self-sorting, self-regulation and higher-order organization and function.
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