I haven't been blogging that much recently ... well to be honest I've had too much work to do.
But as time goes on my ability to cope with the rich experience of daily lab life requires me to rant every so often. So here is today's rant.
There are two approaches to small biology, studying molecules and studying processes. Stay away from the molecule-centric approach!
What do I mean by that?
An easy trap for biologists to fall into is to latch on to their favorite protein and attempt to explain how it functions within the context of a cell. This methodology can sometimes lead to advances, but more often ends up examining the most pedestrian aspects of biology. "Molecule X interacts with Y, molecule X has three domains, molecule X is involved in apoptosis, cell division and development." Yes that's very nice, but it's the context that counts, not molecule X.
Other scientist study processes. Such as ... How does a cell polarize? How does RNA get exported from the nucleus? These lines of thought are much more productive and tend to lead to insightful findings. Before the age of genomics, there was a tendency for some process-oriented biologists, such as the cytoskeletal field, to ignore how molecules regulated certain processes. But that time (I think) is well over. With the ease of obtaining cDNAs, sequences, strains and other tools, it is now trivial to find and study how molecules are directly regulating your process of interest.
So ... if you have set your goal on studying processes, the first question you should adress is "what molecules are involved?" (or as my thesis advisor would say "show me the molecules!") Having identified the various proteins involved in your favorite process you can now piece together the underlying molecular machinery.
Other alternatives? Well three have emerged recently.
1) Big biology. In many ways this method is as mind numbing as studying a molecule. On the surface there are three types of big biologists: those who study the impact of a single molecule on the cell's composition, those who study the effects of larger perturbations on a cell's composition, and those that apply a technique to study the cell's composition. (As an example of the last group would be a lab that catalogues every protein-protein interaction in a cell). These projects are very ambitious, yet tend not to provide any real insightful results. In the end we are swamped with tons of data of unknown quality. This combination (too much data + questionable reliability of the data) make it tough for small biologists to gain any insight. In the best scenarios, data generated from big biology has been used as a tool that can further the research of small biologists. Examples are the genome, databases and strain collections.
2) Synthetic Biology. The idea here is to reconstruct biological processes from scratch. Call it reverse bioengineering. This field is in its infancy and holds great promise. It is unclear however when we will be able to reconstruct complex mechanisms such as the cell cycle or cell migration. One major problem is that evolution is smarter than we are. But probably the exercise is well worth it.
3) Systems biology. We're not sure what this is. Understanding the system of protein networks on a higher level? Peter Soger described it as understanding how modules of proteins act in concert to form signaling modules and other higher order structures. This approach hold lots of promise ... however it could also go the way of other trendy but oversold "new approaches".
OK my time's up.
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A few comments, in reverse order...
1) I find that systems biology types and synthetic biology types tend to blend together and overlap.
2) Big biology does have its uses - I was going to blog on the yeast proteome interaction papers published recently, but never got to it. Shame on me.
3) Studying molecules gives us some of the most useful work for studying processes - for instance, identifying an enzymatic activity, modifications, and the complexes a molecule is involved in is really cool - if we also know that molecule is central to an important process.
OK, that runs down my thoughts for tonight. :)
I think you missed the point.
I don't think I miss the point, so much as I disagree - I think that studying molecules and studying processes are complementary approaches, and not mutually exclusive.
OK you definitely miss the point. Lets take an example. You go to a talk, and there some PI lectures about how his lab is studying a kinase. The kinase does this, the kinase does that, ... blah, blah, blah. This is an easy trap for people to fall into.
It's the categorizing syndrome.
It's simple, you don't have to think much. You IP it, chop it knock it down. In the end your kinase-centric lab just blew itself into mediocrity.
It is much more interesting and insightful to take a cellular process and tear it apart ... to figure out the molecules that are involved. Perform some biochemistry to how the molecules come together to produce a molecular machine ... to see how the machine is regulated by post-translational modifications etc.
PS Synthetic Biology does not equal Systems. You can ask the Endy (synthetic) or Kirschner (systems) labs.
PPS I know Pam Silver has been doing both. But her blinking yeast are closer to synthetic biology. See Sorger's recent work for what Systems biology is really all about ... what he does has NOTHING to do with synthetic biology.
If you have an interesting molecule, why not work upwards? Find out what complexes it might be involved in, what enzymatic reactions it catalyzes, and so on. It's not necessarily the most exciting work, but it's vitally important so that others have blocks to build on. Otherwise, when you're exploring a process, you're likely to get bogged down in the study of numerous proteins of unknown function.
I heard someone say (can't remember who or when) that systems biology is just physiology with a slick marketing campaign.
I agree, and I am taking a very "how does this process work" approach to my thesis project, but note that sometimes I throw my hands up and wish that I'd just picked a damn molecule to characterize and have done with instead of wracking my brain over a really complex problem that I'm probably not going to solve and probably only a hundred people in the world even care about ...
;)
Yeah I've been there. BTW congrats on the wedding.
Perhaps that's why they are so vague about the definition of Systems Biology.
Essay from PLoS Medicine, May 2006
"The Limits of Reductionism in Medicine: Could Systems Biology Offer an Alternative?"
In the first of a two part series, Ahn and colleagues discuss the reductionist approach pervading medicine and explain how a systems approach (as advocated by systems biology) may complement reductionism.
10.1371/journal.pmed.0030208
"The Clinical Applications of a Systems Approach"
In the second of a two part series, Ahn and colleagues provide a practical discussion of how a systems approach will affect clinical medicine, using diabetes as an example.
10.1371/journal.pmed.0030209
NW,
Thanks, those look interesting. There is also a whole series of "opinions" in last year's Cell.
http://www.cell.com/content/issue?volume=121&issue=4
I would modify your statement.
Cell biologists should "stay away from the molecule-centric approach". Of course there has to be someone out there to study important proteins in greater detail. Those people are called biochemists, enzymologists and structural biologists. But I agree, cell biologists (and for that matter physiologists, microbiologists, geneticists etc.) should focus on the bigger picture.
Interesting post!
It may be cynical of me, but I sometimes get the distinct impression that many people claiming to do "process biology" are really in fact doing "molecule biology" with the "process" mainly acting as a post-hoc justification of their work.
Acme,
You structural biologist lover. Point taken. We need some molecule-centric people, but they better stay focussed on the nitty gritty aspects of a molecule, in contracst to domain bashing molecular biologists.
jhutchinson,
Yes there are many of those ... i guess we could call them process posers!