Timely E. coli Engineering a standardised cellular oscillator UQ-Australia iGEM 2011 Regional Jamboree - Asia Inspiration Circuitry Modelling The Future
Our Team Inspiration Circuitry Modelling The Future
Our Team Inspiration Circuitry Modelling The Future
Circadian Rhythm Circadian rhythm regulates: Sleep-wake cycle Body temperature Feeding behaviour and appetite Hormone secretion and metabolism Glucose homeostasis Cell cycle progression Inspiration Circuitry Modelling The Future
Effects of the circadian rhythm Inspiration Circuitry Modelling The Future
Other effects 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Hartman et al. Am J Physiology. 1991; 260: E100-110 Hypertension.2005; 45: 874-879 Inspiration Circuitry Modelling The Future
Human circadian circuit Key features: • Time delay • Negative feedback loop Gallego et al. Molecular Cell Biology. 2007; 8: 139-148 Inspiration Circuitry Modelling The Future
Mammalian Model Tigges et al. Nature. 2009; 457: 309-312 Inspiration Circuitry Modelling The Future
Prokaryotic Models Atkinson et al. Cell. 2003; 113: 597-607 Inspiration Circuitry Modelling The Future
Prokaryotic Models • Simpler circuit • Dual response promoter Stricker et al. Nature. 2008; 456: 516-520 Inspiration Circuitry Modelling The Future
Our system araC plac/ara glnG pBAD lacI glnAP2 Inspiration Circuitry Modelling The Future
glnG GlnG P S pSB1C3 Inspiration Circuitry Modelling The Future
araC pSB1C3 araC P S Inspiration Circuitry Modelling The Future
lacI lacI P S pSB1C3 Inspiration Circuitry Modelling The Future
Mathematical Model araC plac/ara glnG pBAD lacI glnAP2 Inspiration Circuitry Modelling The Future
Model Analysis • Modelling of a novel synthetic system • Kinetics sourced from pre- existing work Limited by differences in experimental conditions Inspiration Circuitry Modelling The Future
Gene dosage effects Tigges et al. Nature. 2009; 457: 309-312 Inspiration Circuitry Modelling The Future
Chromosome integration 1 1 1. Landing pad - Use a pre-determined landing site to target our constructs 2 2. Homologous recombination - Via identity with the landing pad site 3 3. Integration! - Now we have no need to worry about fluctuations in gene dosage Kuhlman et al. Nucleic Acids Research. 2010; 38(6): e92 Inspiration Circuitry Modelling The Future
Applications • Standardised platform for modeling oscillating systems • Periodic medicine: potential drug or hormone delivery system • Biological Battery Cell: Generating current through periodic stimulation of ion channels Inspiration Circuitry Modelling The Future
…And along with the science Biofutures + pain Inspiration Circuitry Modelling The Future
…And along with the science • Share your human • Catch up (and practices and collaborate!) with iGEM’ers outreach activities Inspiration Circuitry Modelling The Future
UQ iGEM • Oscillatory circuits are important in nature • We are standardizing the biological ‘clock’ • Outreach is an important part of science too! Inspiration Circuitry Modelling The Future
Thank You Inspiration Circuitry Modelling The Future
Kuhlman & Cox (2010) Chromosome Integration Inspiration Circuitry Modelling The Future
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