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Leave any questions:

1) Are we sure that others haven't finished/worked on bio-clock? Many other groups considered building a bio-clock (eg. IGEM2006 Imperial) before but abandoned it due to various reasons. We may be able to get ideas on how to build a bio-clock from partially completed projects of others.

2) Our focus now is on how to build a bio-clock. If we have a bio-clock, what is its uses/applications?

  • It acts as a fully customisable method of temporal regulation (allows us to control what genes are switched on when)
    • This seems like a simple goal but is actually more useful than it first appears. When people think about what a gene does, they generally think along the lines of "this gene encodes protein X which catalyses reaction Y" but the reality is that the function of a gene is also dependent on the where and when (the regulation) of the gene. If complex systems are to be created through the use of synthetic biology, there must first be complex regulatory systems in place to control them.
  • On your second point, a lot of complex biological systems that we observe in Nature now have in-built clocks such as a circadian clock. My speculation is that due to the light/dark cycle on Earth, it affects a lot of organisms (eg. terrestrial organisms that are exposed to light). However, organisms that are not affected by external cycling signal such as the light/dark cycle, do not seem to have the need to evolve a clock such as a circadian clock in this case. Most people will say that E. coli bacteria are an example of complex biological systems but they seem to lack a clock that is responsive to light. It is not even known to me whether they have in-built clocks of any kind that perhaps respond to other oscillating signals, which are persistent in their environment. If they really have no in-built clocks, then the argument that complex systems need to acquire a clock for complex regulatory systems may not hold.
    • One important point of difference between a circadian clock and our models is that a circadian clock has only two phases (light/dark) whilst our designs would have two phases (ON/OFF) but with a memory as well (ON1/OFF1/ON2/OFF2...etc.). As such, a circadian 'clock' is not really a clock but an oscillator, whilst our designs behave like a real 'clock' because they would know what state they are in and move to the next state on the signal.
      • You are right to point out that a biological clock such as a circadian clock is not a clock by the following Merriam-Webster definition of clock:

a device other than a watch for indicating or measuring time commonly by means of hands moving on a dialect; broadly : any periodic system by which time is measured. However, on the same page of the dictionary, a clock is also commonly used to mean biological clock. The context on my point is a biological context but perhaps, I should have been explicit in saying biological clock all the time. A circadian clock describes the oscillation of biochemical signal in response to light/dark cycle and for this part, really, it is just an oscillator. However, are we sure that the oscillating signal isn't passed on to other biochemical components to tell 'time' in a biological sense? Time is relative and in biological organisms, their clock run on different real-time. Why do organisms evolve circadian clocks (oscillators)? Could telling time be a reason?

3) Are we sure that one of the model synthetic biology model organism, E. coli has no in-built clocks?

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