Team:McGill

From 2009.igem.org

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=='''Welcome to the 2009 McGill iGEM Team homepage!'''==
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=Project Overview=
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Welcome to Quebec's only iGEM team! Our team is made up of a group of motivated students and faculty from McGill University in Montreal, Quebec, Canada. We have been hard at work preparing for this year's competition. The following webpages should give you a brief oversight into what we have accomplished this year!
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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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=='''Project Description (General)'''==
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We are interested in exploring the biology of intercellular signaling. The human body is composed of trillions of cells, which have to communicate with each other over long distances. We are interested in investigating the effect of distance on the signaling dynamics. Although there are many cellular communication mechanisms we decided to focus on chemical signaling. Specifically, we are interested in investigating the dynamics of activation-inhibition signaling. This occurs when a cell synthesis and releases a chemical that is capable of diffusing to a second cell and activating production of an inhibitory chemical which diffuses back to the first cell and inactivates synthesis of the former chemical (as illustrated in the following diagram).
[[Image: Mcgill09Projectfig1.png|frame|center|Figure 1 – The diffusible proteins A and B are involved in an opposite feedback mechanism]]
[[Image: Mcgill09Projectfig1.png|frame|center|Figure 1 – The diffusible proteins A and B are involved in an opposite feedback mechanism]]
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We have explored this system using two approaches: mathematical and microbiological. We began by developing a mathematical model allowing us to perform ''in silico'' experiments of the system. Furthermore, we engineered two strains of bacteria to recreate this system allowing us to begin validating our mathematical model.
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'''Dynamics'''<br />
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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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Aside from simply gaining insight into this type of signaling we also hoped our investigations would lead to a novel type of biological sensor! Explore the following pages for a more detailed explanation of our project!
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<hr/>
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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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Latest revision as of 06:22, 21 October 2009


Home Home Team Team Project Notebook Results Sponsors

Welcome to the 2009 McGill iGEM Team homepage!

Welcome to Quebec's only iGEM team! Our team is made up of a group of motivated students and faculty from McGill University in Montreal, Quebec, Canada. We have been hard at work preparing for this year's competition. The following webpages should give you a brief oversight into what we have accomplished this year!

Project Description (General)

We are interested in exploring the biology of intercellular signaling. The human body is composed of trillions of cells, which have to communicate with each other over long distances. We are interested in investigating the effect of distance on the signaling dynamics. Although there are many cellular communication mechanisms we decided to focus on chemical signaling. Specifically, we are interested in investigating the dynamics of activation-inhibition signaling. This occurs when a cell synthesis and releases a chemical that is capable of diffusing to a second cell and activating production of an inhibitory chemical which diffuses back to the first cell and inactivates synthesis of the former chemical (as illustrated in the following diagram).

Figure 1 – The diffusible proteins A and B are involved in an opposite feedback mechanism

We have explored this system using two approaches: mathematical and microbiological. We began by developing a mathematical model allowing us to perform in silico experiments of the system. Furthermore, we engineered two strains of bacteria to recreate this system allowing us to begin validating our mathematical model.

Aside from simply gaining insight into this type of signaling we also hoped our investigations would lead to a novel type of biological sensor! Explore the following pages for a more detailed explanation of our project!