Team:Edinburgh/Networking

This was an old idea considered in week 1.

Networking bacteria, people and other stuff with BioTweets

Intro

First of all, IANAB – I am not a biologist. Now...

Biological computation is quite popular with iGEM, and some teams in the past have looked at it, so some BioBricks already exist for this purpose. But why bother at all? Well, in theory, if we can make calculations of some sort within a cell / using a group of cells, then these can be replicated easily and computational power can grow exponentially. This in turn can lead to solving 'NP-complete problems' – a group of problems which take exponential time to solve, and are of fundamental meaning to information theory.

Networking Bacteria

The idea is to make cells communicate with each other, as if in a circuit, and thus calculate a logical function – e.g. NAND (= NOT AND), i.e. the output is TRUE if and only if two inputs are FALSE. (NAND is special, because an arbitrary logical function can be 'dismantled' into a series of NANDs – see [http://en.wikipedia.org/wiki/NAND_gate Wikipedia on NAND]). That can be used, for example, in a sensor which needs to respond to a specific set of stimuli (say, stimulus A and B present, but not C; or A and C but not B, etc.)

The input could be in various forms – e.g. light or a chemical (or temperature, probably not used in iGEM yet [http://www.nature.com/emboj/journal/v25/n11/full/7601128a.html paper on thermoswitches]). The output, well, other teams have used light or secreting chemicals, but my idea was to (if it is at all possible, IANAB) connect cells using some sort of nanotubes (NOT carbon nanotubes, but something like pili? IANAB!). This way, we can do direct cell-to-cell communication as opposed to cell-to-environment and environment-to-another cell. This lets us make another 'layer' of cells, which take input from the previous 'layer' and so on (whereas if the output is secreted into the environment, we have little control over which cells take it up). That would be an improvement on quorum sensing.

So, in general, we could use: BRIDGE (last year's protocol), nanotubes (freaky experimental stuff!), or conjugation (which is well-documented and used for exchanging plasmids).

1. Cells may be engineered to communicate within one population or between two populations, even between species(!) and that sounds fancy.
2. Maybe it would be worth trying to design surface antibody that would bind to membrane protein causing binding of two cells. Membrane protein can be then either native to the species or not. The two inputs could regulate expression / localisation = membrane insertion / activity of antibody and antigen. Only if both were present you could link cells together.
3. It could be awesome to design antigen protein (maybe membrane kinase) to be turned on/off upon binding to antibody. It could then activate some intracellular processes with some easy to read output (GFP/luc expression, colour reaction)

Modelling

This is the cool part, because here we could try to model something non-biological that actually exists and works (i.e. a logic device, which is a part of every computer) using biology.

Human Aspects - Networking People

Here we can exploit the 'networking' aspect of the project – talk about sharing our knowledge with high schools, other teams (not to mention getting a Twitter account for the team :P - last year Stanford had Twitter as part of their human practices and it seemed to be very well received by judges) Also, as mentioned above, using bacteria to compute stuff has the potential to advance other fields, like Informatics. Also, this can be used in diagnosis.

References

1. An absolutely amazing yeast which can do logic [http://www.nature.com/nature/journal/v469/n7329/full/nature09679.html from Nature]
2. Stanford's 2006 project, where they made a logic gate inside a cell from iGEM
3. Other logic gates from Missouri Western
4. And a recent paper from [http://www.sciencedirect.com/science/article/pii/S009286741100016X Cell] about nanotubes between B.subtlis