Thursday, January 27, 2005

Semi-random thesis thoughts

As part of trying to accelerate the process of getting my PhD, I've already been doing a lot of thinking about what specific project I want to do my thesis research in. One area I've been exploring is extending some work that has been done in building artificial genetic circuits which make bacteria "talk" to each other. I've written about quorum sensing before, but here's the quick recap: certain bacteria make chemicals that diffuse out of the bacterium that made them and into other bacterial cells and cause the recipient bacteria to react in some way. This mechanism has been used to do nifty things like build an artificial genetic circuit which causes bacteria to regulate their own population by basically committing suicide if there are too many of them [here's the PubMed link to the paper if you're really interested].

While these cell-to-cell communication circuits are cool and all, they suffer a bit from the fact that they're basically serial communication ie they're a bit like having a conversation where you can only answer "yes" or "no" to questions -- you eventually get to the point, but it takes a while. I've been thinking about making this a more powerful system such that you can actually exchange whole "sentences", so to speak. I have a decent idea, on paper, how to do this but I suspect that actually trying it in the lab would become painful pretty quickly, especially given my lack of lab experience. It's a project that I'll probably keep hammering away at during my current rotation with Tom Knight, but I'm also thinking about other stuff.

The other area I'm getting interested in developmental biology, which is concerned with how you make a whole critter when all you've got to at the beginning is a single cell. On the face of it, it's just insane that you can pack the entire blueprint for something as big as an elephant, as weird as a duck-billed platypus [a mammal that lays eggs yet suckles its young after hatching] or as, ahem, "smart" as GW Bush into a single cell that you can't even see without a microscope.

There are oodles of observational data [ie what happens] about how certain model organisms [like the fruitfly, a particular species of frog, the mouse, humans etc] develop, as well as lots of data about what individual genes are involved in developing the adult body plan. However, so far there are fairly few large-scale "wiring diagrams" that tie all the bits involved together and really give a good global explanation of how & why you get from the fertilized egg to the various lifecycle stages. The only thing I've been able to find that comes close is some work out of Caltech, by Eric Davidson's group, which has mapped out this sort of diagram for the sea urchin. [PubMed reference to the paper]. A look at the number of authors on that paper should give you an idea of how much work it is to do this for something as "lowly" as a sea urchin; "higher" animals will probably have an even more complex set of interactions, requiring correspondingly more work, though that remains to be proven.

What appeals to me about this area of biology is that
a) I've always been interested in how you get "emergent" behavior [like a whole animal] out of the interaction of lots of little "dumb" parts [like cells] that are just following fairly simple rules, ad animal development is a really cool example of that
b) there is lots of room for computational work: to attack the problem you need to do large-scale experiments to figure out what genes are active and perform computational analysis of the results, as well as build a computational model of the gene network to explain the progression through the various stages of development. In other words, lots of fodder for a computer geek like me.

So, I'm in the process of reading "Developmental Biology" and whatever papers I can find on PubMed to see whether this is something I want to pursue further. I'm also going to talk to a professor at Harvard, Radhika Nagpal, since this is an area she's interested in [as a bonus, she has good connections to Drew Endy and Tom Knight, having worked with both of them when she was a postdoc at MIT].

2 Comments:

Blogger - i said...

A parallel bus, one type of signaling molecule per pin? N possible molecules transmitting log n bits of information? Message encoded by a polymer?

9:47 PM  
Blogger Alex said...

Message encoded by a polymer.

9:41 AM  

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