Team:McGill/Project

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=='''Project Goals'''==
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Our interest in the dependence of separation distance in activation-inhibition intercellular signaling stems from the possibility of observing oscillations in chemical concentrations over time. This work will not only give us a better understanding of how natural biological systems operate but could also lead to the design of a novel type of biological sensor.
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== '''Project Overview''' ==
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Imagine a sensor composed of a lawn of bacteria, which under normal conditions are all fluorescing at steady state. However once the system is exposed to a foreign substrate (substance to be detected), the dynamics of the system suddenly switch from steady state to oscillatory, which can be observed and noted by a technician.
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'''Activation-Inhibition Coupling'''<br />
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:The biological system to be investigated consists of two spatially separated populations of cells, each expressing a different protein; here named A and B. Protein A diffuses out of the first population of cells and into the second where it stimulates the production of protein B, which is another diffusible protein that can travel back to the first population and inhibit the production of protein A.
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[[Image: Mcgill09Projectfig1.png|frame|center|Figure 1 – The diffusible proteins A and B are involved in an opposite feedback mechanism]]
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'''Dynamics'''<br />
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This idea is still in the planning stages. We have begun exploring this system through two approaches: mathematical and microbiological. We have developed a partial differential equation based model in order to gain insight into the natural dynamics of the system as well as how they vary with perturbations to parameters. In parallel, we have engineered a microbiological system in order to begin carrying out experiments to validate our modeling results. The following pages describe our progress in these two themes.
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[[Image: Mcgill09Projectfig2.png|frame|right|Figure 2 – Mathematical model of activation-inhibition
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coupled cellular signaling, where the dashed line represents protein A and the solid line represents protein B<sup>1</sup>.]]
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This type of cellular signaling is known as activation-inhibition coupling, and although it can seem fairly mundane,
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some interesting dynamics can result. Figure 2 illustrates the mathematical modeling of this system where periodic oscillations were observed. The type ofbehavior observed depends on the parameters of the system, including the rate
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of diffusion of the proteins, the distance between the two cell populations, the sensitivity to transcriptional regulation and several others.
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'''Hypothesis, Goals, and Potential Applications'''<br/>
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To date, the kinetics of this type of cellular signaling has only been theoretically analyzed using mathematical tools. We aim to provide experimental observations of the system at work. Furthermore, we plan on extending the mathematical framework from a 1 dimensional model to 2 dimensions. In the 2D setup, the two populations of cells will be cultured together with random spatial distribution at varying densities. We expect to see several forms of dynamics depending on the density: at low densities, only local interactions will become significant and pockets of oscillations will be observed; at high densities, a steady state of activation will be achieved; however at intermediate densities, we expect to observe waves of activation propagating through the cell culture. The mathematical model will drive the design of experiments to verify these claims. These investigations could yield the foundations for a novel type of biological sensor. Exposing the cultured cells to a particular compound could alter the qualitative dynamics of the cellular signal: switching from steady state activation to propagating waves, thus alerting the investigator to the presence of the compound.
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===References===
 
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'''1.''' Shymko, R., and Glass, L. (1974). Spatial switching in chemical reactions with heterogeneous catalysis. The Journal of Chemical Physics 60, 835.
 
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== '''Project Details'''==
 
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=== The Model ===
 
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'''Equations'''
 
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      <p><a href="https://2009.igem.org/Team:McGill/Modeling" target="_blank"><img    src="https://static.igem.org/mediawiki/2009/8/89/Mcgill09eqn.png" width="300" height="200" /></a></p>
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      <p><a href="https://2009.igem.org/Team:McGill/Experimental" target="_blank"><img src="https://static.igem.org/mediawiki/2009/e/e5/Mcgill09exp.png" width="300" height="200" /></a></p>
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      </div></td>
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        <td><div align="center"><p><a href="https://2009.igem.org/Team:McGill/Modeling" target="_blank"><b>Modeling</b></a></p></div></td>
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        <td><div align="center"><p><a href="https://2009.igem.org/Team:McGill/Experimental" target="_blank"><b>Experimental</b></a></p></div></td>
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=== Biology & Experiments ===
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Latest revision as of 07:33, 21 October 2009


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Project Goals

Our interest in the dependence of separation distance in activation-inhibition intercellular signaling stems from the possibility of observing oscillations in chemical concentrations over time. This work will not only give us a better understanding of how natural biological systems operate but could also lead to the design of a novel type of biological sensor.

Imagine a sensor composed of a lawn of bacteria, which under normal conditions are all fluorescing at steady state. However once the system is exposed to a foreign substrate (substance to be detected), the dynamics of the system suddenly switch from steady state to oscillatory, which can be observed and noted by a technician.

This idea is still in the planning stages. We have begun exploring this system through two approaches: mathematical and microbiological. We have developed a partial differential equation based model in order to gain insight into the natural dynamics of the system as well as how they vary with perturbations to parameters. In parallel, we have engineered a microbiological system in order to begin carrying out experiments to validate our modeling results. The following pages describe our progress in these two themes.


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