Team:Groningen/Brainstorm/Growth Control


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Bacteria have a choice between using nutrients for growth or for the production of (commercially) valuable proteins. Being able to control the bacterial growth cycle and inducing a premature stationary phase will create the possibility to spend more time producing, using less nutrients for biomass and more for desired production. Stationary phase is nothing more than a stop in an increase of cell numbers by cell death being equal to cell growth. Normally this is induced by the limitation of available nutrients or by means of quorum sensing in response to high cell density. With this knowledge, a culture can be created that can respond by limited cell death in response to an added molecule that mimics the response to high cell density.

See also Chemostat
One of the most important features of chemostats is that micro-organisms can be grown in a physiological steady state. In steady state, all culture parameters remain constant (culture volume, dissolved oxygen concentration, nutrient and product concentrations, pH, cell density, etc.). Because obtaining a steady state requires at least 5 volume changes, chemostats require large nutrient and waste reservoirs. Creating biological "chemostat" would circumvent these drawbacks.


What we want to reach is an early stationary phase that is inducible and can be relieved to continu onto its natural stationary phase upon depleting its nutrients. To be able to leave to early stationary phase the inductor needs to be degradable or blockable. However, to speak of an actual phase the degradation or inhibition should proceed slowly so not to end the phase too soon.

In undertaking such an endeavour there are several approaches possible, one is to create a switch that could simply stop cells from reproducing and focus them on to production. The other is to create a culture that upon induction begins to oscilate between cell death and cell growth. Because creating either possibilities should yield some difficulties, the project could be divided into three parts.

  1. Inducing an early stationary phase (that focusses its metabolism on protein production, visualized by GFP)
  2. Leaving the early stationary phase (leaving the early stationary phase should be optional in practice)
  3. Creating an oscilating culture that remains between predefined limits.

Possibilities to think of might be a time switch so to continu growing after a set period of time, or continu growing as soon as certain demands are fullfilled (certain amount of production). However, both ways of leaving the early stationary phase are then induced intrinsically and not determined by us. The same problem for the idea of adding a substance that induces the production of an autoinducer simultaneous with an slow promotor of an autoinhibitor, as the concentration of the autoinhibitor rises to a certain point the effect of the autoinducer will be block sufficiently to continu growing.

It would be nice to work with NICE

Previous contests

Quorum Sensing

Cell cycle

Cell death

Parts in the Registry of Standard Parts:

Quorum sensing

  • BBa_K104001: Sensor for small peptide Subtilin
  • BBa_I13211: Biobricked version of the natural Lux quorum sensing system
  • BBa_T9002: AHL to GFP Converter
  • BBa_K09100 Receiver for AHL and Outputs GFP when AHL is present

Cell cycle

Cell death

Related Literature

Quorum sensing

In this paper, the molecular mechanism underlying regulation of nisin and subtilin production is reviewed.
Addition of N-acylhomoserine lactone in the exponential growth phase, regardless of cell density, induces a repression of cell growth of P. aeruginosa
In this study Competence stimulating peptide is shown to initiates release of DNA from a subfraction of the bacterial population, probably by cell lysis.
In this study they created a synthetic ecosystem with bi-directional communication through quorum sensing which regulate each other's gene expression and survival via engineered gene circuits.
In this study they have built and characterized a 'population control' circuit that autonomously regulates the density of an Escherichia coli population, that is lower than the limits imposed by the environment. The cell density is broadcasted and detected by elements from a bacterial quorum-sensing system, which in turn regulate the death rate
In this study they created two colocalized populations of Escherichia coli that communicate with each other and exhibit a “consensus” gene expression response. Because neither population can respond without the other's signal, this consensus function can be considered a logical AND gate in which the inputs are cell populations.

Cell cycle

A study that showed certain promotors involved in amino acid biosynthesis being downregulated when compounds of the involved pathways were added.

Cell death


In this work, they demonstrate the biological relevance of a method specifically developed to support the design of synthetic gene networks.
A review of past and present of computational modeling of cell-cycle regulation
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