Team:Imperial College/Applied Design
Applications
Applications
Hybrid digital-biological computation
Biocontainment (Environment) Preventing the escape of GMOs is a major public worry and obstacle to their implementation. This device prevents the escape of GMOs using an electrical “cage” where an oxidising potential causes expression of a toxin or growth inhibitor. This operates similar to how an electric fence restrains livestock. A proof-of-concept for this device was confirmed. Our transcriptional repressor pSoxS mutant (BBa_KXXXX) could be used to create a more robust device where cells require an electrical stimulus to survive.
Hybrid Digital-Biological Computation (Information Processing) Integrating electronic and biological computation with our device would improve the complexity of synthetic biology devices without increasing the metabolic burden imposed on the biological chassis. For example, a fluorescence camera could be connected to our electrogenetic system, with the information it records being processed via an in silico feedback loop which changes the electrode array’s output. An example of this would be to use the in silico feedback to model an activator-inhibitor system, with parameters of the feedback function being altered to search for Turing patterning behaviours.
Spatially structured cocultures (Foundational Advance) The separation of labour in co-cultures provide numerous advantages over single-cell cultures. Although the complex functions of eukaryotic organs cannot be achieved without patterning. PixCell could be used for spatial patterning of co-cultures to improve their function, for a segregated co-culture of cells resembling the α- and β-cells of the pancreas.
Fabric Printing (Manufacturing & Environmental) The fabric dying industry involves the use of various toxic and environmentally damaging chemicals. Patterned expression of dyes in bacteria using the PixCell electrogenetic system would provide an affordable and environmentally friendly fabric printer. We developed a proof-of-concept of this system with the production of melanin which can be used to dye wool-cloth, but recent publication show it could also be used for indigo dyeing of denim.
Bioelectrical Patches (Therapeutics) Transdermal are currently used to treat a variety of diseases, such as L-DOPA patches to treat Parkinson’s disease. Although existing patches function passively and are expended after a day. A microelectrode array could be used to generate an active transdermal L-DOPA patch with a longer lifetime utilising a previously reported L-DOPA synthesis pathway.
Efficient Mutant Selection (Foundational Advance) The efficiency of directed evolution experiments is dependent on adequate selection and separation of successful mutants. Previous literature shows how evolving various activities in protein, DNA and RNA can be linked to the expression of a transgene. By linking successful mutations to SoxR expression and bringing the flagella control gene CheZ expression under the control of pSoxS you can create a system in which successful mutants would tumble around electrodes. This not only allows for easy isolation of mutants, but by scanning various electrode potentials you can test a series of selection pressures in one reaction to select for libraries of mutants with various activities. Moreover, it hasn’t escaped our attention that his system can be used as the basis of an antibiotic-free selection system.
Biomaterial Patterning (Manufacturing) Biomaterials are normally produced in liquid-phase and then undergo classical industrial processing to form the fibres used in manufacturing. Our electrogenetic system provides a method of precise spatial patterning which could be used to allow printing of high-value, processing-free biomaterials such as collagens or hyaluronan into ready-to-use defined shapes
Gene Activity Dosing (Foundational Advance) Selecting an optimal expression level of a gene in synthetic biology is difficult, inefficient and costly when dosing the gene using a standard chemical inducer system. Activating transcription of the gene of interest along with GFP in our electrogenetic circuit would allow for easier selection of gene dosing. Electrode potentials could be varied across an electrode array, with the GFP fluorescence from the position with optimal dosage being used to calibrate this expression level to a constitutive promoter from the anderson set.
Bioreactor Control (Manufacturing & Food & Nutrition) SHIV CAN YOU WRITE THIS ONE.
Tissue Engineering (Therapeutics / Food & Nutrition) Although porting this electrogenetic device into a mammalian system may prove difficult, a series of redox-responsive transcription factors are found in mammalian cells which could be used to build a cognate system. One such example is USF-1 which responds to DTT in its reduced form only. By applying the spatial control achievable with electrogenetics, such a system could be used to control cell-fates in embryonic stem cells for organ transplants. Alternatively it could be used in the production of synthetic meat, which if an efficient method existed would allow for significant reductions in the humanity’s carbon output.
