Paris Project Description

From 2007.igem.org

Revision as of 14:54, 4 July 2007

Under construction

The idea is to make multicellular organism out of bacteria. This simple organism will have two distinct types of cells. The first one would be the germline, the other one the soma. The germline will be auxotroph for a given nutriment, which will be provided by the soma. The soma will differentiate from the germline and will be unable to divide. In this way, there is a need for a part of the germline to differentiate into soma in order to feed the rest of the germline. Hence, the soma doesn't exist without a germline to generate it.

Such an organism would have two main perspectives. Firstly, it could help understanding how the first multicellular organisms appeared. What could be the underlying mechanisms? In what conditions could multicellularity confer an advantage?

An other interest of a bacterial multicellular organism, is that it could allow optimizing the production of compounds deleterious to the cell. If you try to optimize the production of such a compound in a classic bacteria (E.coli for instance), you will reach a trade off between the production of your compound and the growth of the cell. The synthetic organism could in part bypass this problem. It could indeed be modified so that the soma only will produce the noxious molecule. If their is a way to screen for the production of this molecule, we can then select the germline whose soma would have the best yield. As long as the production doesn't impair to much the capacity of the soma to feed the germline, the optimization can go on. Thus, their is also a trade off in this case, but it might very well be more favorable to the optimization than the trade off between production and growth. At least, this is worth testing.

Of course, all this is only possible if the germline is not affected by the production of the soma. Compounds that could be optimized in this way are thus constrained to molecules that can be noxious in the cell, but that do not affect it to much if in the medium.

We also came up with the idea of modifying the synthetic organism so that we would be able to induce the differentiation of all the germline into soma in a secured way. Why would we want to do that ? Well, in a security perspective, we may not want to relieve a transgenic strain in the environment. But it would be acceptable to do so if we are sure that the cells we relieve are not able to proliferate. In this view, we could relieve in the environment, what would correspond to our "soma". Those cells aren't able to divide and their effect is limited in time since they will die after approximatively 2h . This is the "security device" part of our project.

Finally, the last part of our project would be to bring together the synthetic organism, the optimization of a compound noxious to the bacteria, and the security device. To do so, we'd like to optimize the production of triglycerides in the soma cells of our synthetic organism. We would then be able to differentiate all the germline of our organism into soma in a secured way. Those super triglycerides-producing-not-able-to-divide cells could then be ingested. They would stock triglycerides out of fatty acids, and the fatty acids they would stock would be as many fatty acids that you will not absorb! Eat fat, don't get fat !

How can we define a multicellular organism ?

There is no universally admitted definition. Wikipedia gives: "an organism (in Greek organon = instrument) is a living complex adaptive system of organs that influence each other in such a way that they function in some way as a stable whole."

For us, the organs will simply be different cells. The definition we retain is that of a multicellular entity with different types of cells fulfilling different complementary tasks.

In most organisms, some cells differentiate to realize a function useful for the organism. By useful, we mean that it will give a better fitness, or in other terms, that it will help producing more offspring. The specialized cells are usually not the same than the ones reproducing the organism, and they loose this ability. Thus, their is a notion of sacrifice of some cells to the profit of those dedicated to reproduction. The cells are able to reproduce the organism represent the germline, the ones which specialize and loose this ability represent the soma.

How to proceed ?

The question is: how can we make a cell differentiate into two distinguished lines? According to us, the answer is the Cre/loxP system. We will introduce a special genetic construction into the bacterial chromosome; the excision of a cassette framed by loxP sites will lead to the differentiation of these cells into soma. In other words, the original germ cell gives a soma cell when a particular cassette is excised consequently to Cre/LoxP-system action. The construction could be simply represented in that way: