Joel Bader of Biomedical Engineering
deconstructs the numbers game of computational biology
There's a difference between "computational biology" and bioinformatics, right?
BADER: The fields are very close, but bioinformatics is more database and statistics oriented, whereas computational biology is more about modeling and simulation. They overlap, and sometimes it's a toss-up whether something is one or the other. I guess if you are using a lot of disk space and input-output, that's bioinformatics; if it takes a lot of CPU time and less database, that's computational biology.
Would you call computational biology an emerging discipline?
BADER: Well, people have been doing it ever since there have been sequences to analyze, but it's really grown lately. Some things people now call computational biology used to be called computational chemistry after the analysis of protein structure, protein folding and simulations that used to go on in chemistry departments. Things get new names as time goes on.
Since the field is relatively new, do you see an age disparity in who uses it?
BADER: I don't think age has anything to do with people's ability to accept or take advantage of the advances on the informatics side. It's not so much that people must change to get expertise on the computational side, but more that your mindset has to change so you can take advantage of these genome-scale resources and learn to use them well.
Do engineers approach biological questions differently?
BADER: Biologists observe how a system works in order to figure out why it works the way it does – they make predictions based on their observations. Engineers, on the other hand, set out with a finished product in mind. They want something to work in a certain way and go about designing it.
Why “design” biology?
BADER: By custom building, or designing genomes we can figure out whether a certain part of the genome has some sort of cryptic function. For example, yeast cells don’t do alternative splicing, which means that they shouldn’t need introns, but they still have them. Jef Boeke and I are trying to re-build the yeast genome without introns to see what happens to the cells. If we find that yeast don’t need introns, our next step will be to see if they need splicesomes.
So you can take away genes – can you also add genes?
BADER: Of course! In fact, I am currently co-advising a group of Hopkins undergraduates who are entering the International Genetically Engineered Machines (iGEM) competition to do exactly this: build synthetic genes. This student-led initiative aims to produce cells that exhibit new, unusual, and often whimsical properties by synthesizing multiple genes that work together along with mechanisms to regulate their expression. It’s a remarkably ambitious undertaking! 2008 is the first year that a Hopkins team has entered this competition and they will be competing with teams from schools all over the world in November.
What genes can be synthesized?
BADER: If you can think of it, we can try to synthesize it! Some of the projects that have been presented in past iGEM meetings include genes that get cells to flash different colors or genes that can take pictures via a photosensitive metabolic reaction that deposits silver on a photographic plate. You also get some more practical entries like cells that produce biofuels or cells that remove pollutants from their surroundings. One group got E. coli to glow a different color if a toxic chemical was present. The competition should be great – I’m looking forward to it!