Posted: 03 Aug 2008 07:00 PM CDT
Two weeks ago, an interesting commentary by Paul Nurse, came out in Nature.
The bottom line? We need to change how we study and understand cellular signaling cascades.
First, some background. Cellular function is governed by a network of protein interactions that act like an information processing device. These devices sense external inputs, such as cell signaling factors, pH, nutrient availability and temperature, and they regulate a vast number of different cellular responses such as changes in morphology, alterations in the metabolic state, the modulation of cell division, or the regulation of cellular differentiation. These information processing devices are composed of bioactive molecules such as proteins and functional RNAs.
Traditionally these devices have been known as signaling cascades. In most papers and text books they are represented by flow charts. Molecule X activates molecule Y, molecule Y inhibits molecule Z, etc. Often one uses the metaphor of a river so that molecule Y is downstream from molecule X and upstream of Z. Sometimes small molecules such as cAMP or calcium spread the signal, other times its lipids, RNA but the main players are usually proteins. Within the pathway each player activates, inhibits or destroys the next in line. Sometimes the upstream molecule alters the localization of the next protein in the pathway, other times it modifies these downstream components by adding a small reactive group (e.g. a phosphate), a small peptide (e.g. ubiquitin), or by modulating some catalytic activity (e.g. activating GTP hydrolysis). Once in a while a molecule at the end of the pathway will alter the activity of molecules on the top of the cascade. These feedback loops give these signaling pathways a rheostat like ability. Other times the pathway may branch (molecule X activates molecules A, B and C), and other times the pathways converge. Some pathways "crosstalk" to other pathways so that signals that affect cell division also tweak signals that influence cell suicide. In addition the levels of each player can change. Gene expression and protein turnover thus play critical roles in determining how effective a signaling cascade can propagate or inhibit a signal. As a result, different cell types vary in their interpretation of any given signal. It's why a gut epithelial cell differs from a kidney epithelial cell.
But is this the best way to think of these signaling cascades? With the advent of big biology, we are discovering that most signaling proteins can influence the state of almost every other protein in the cell. Once we had a clear picture of signaling, but now our view resembles more and more a bowl of spaghetti. Naturally we must question whether all these putative links exist and whether they are important.Read the rest of this post... | Read the comments on this post...
Posted: 03 Aug 2008 12:46 PM CDT
BioInform has a report (sub reqd, or get it from the Google cache) on a special session on scientific publishing organized my Scott Markel at ISMB. Since that is a topic of particular interest to bbgm and bbgm readers, thought I’d give it a read and find out if there were any new insights there.
I won’t delve into all the specifics, but it is clear that there is a desire in the community to make scientific publication as machine readable as possible. As has been discussed many times here, scientific research is a treasure trove of information and the content contained within papers and other forms of publishing should become part of the data that we try to mine and correlate, and in the long term it’s not just the text, but as pointed out in the article images and other datasets as well.
Mark Gerstein in particular brings up some points which make a ton of sense, and to a degree are somewhat obvious. That we still need to debate them is the part that makes me frown. Wouldn’t it be nice if we could take some of those ideas and thoughts for granted? For example
The part that people don’t seem to grasp, or at least it didn’t jump out to me is that for text-based documents, we have a database, one called the world wide web. Via DOIs and other identifiers, each paper is an addressable resource. Given the right structure and the right APIs it’s a data mashup waiting to happen. Or if you structure things the right way, and want access to a nice n-tuple data store, use something like Freebase or Talis as a backend platform
But I agree with Matt Cockerill as well. We need better authoring tools, and authoring tools need standards for markup and structure. I am not sure where this comes from and how this will be implemented. Unfortunately, we all still write our papers in Word. The LaTeX crowd, or the HTML crowed would probably be happy providing some markup (it doesn’t have to be too heavy).
I won’t even debate open access vs. closed access. In my mind it is no longer a debate. It is good to hear publishers talking about online journals, and about integrating other media formats into publications.
Posted: 03 Aug 2008 08:20 AM CDT
The recent SNP association report, “Identification of loci associated with schizophrenia by genomewide association and follow-up“ (doi:10.1038/ng.201) by O’Donovan et. al, - an analysis of more than 370,000 Affymetrix SNPs on a population of 479 affected individuals - finds strong evidence for rs1344706 in the zinc finger protein 804A (ZNF804A). One clue to the otherwise inscrutable history of this gene may lie in the findings of a yeast 2-hybrid screen where ataxin-1 was used as a bait. Mutations in ATXN1 can give rise to Spinocerebellar Ataxia, a degenerative condition of the cerebellum and spinal cord. Such profound developmental deficits, even if weakly expressed would be consistent with the many cognitive difficulties experienced by patients with schizophrenia.
Posted: 03 Aug 2008 06:20 AM CDT
We’ve reached the end of another week here on Bitesize Bio, so let’s close with the usual survey of what’s happening Around the Blogs. Luckily, the post titles speak for themselves…
Which baby do you want? A dilemma for the 21st century parent-to-be
How to blog, get tenure and prosper: Starting the blog (Anthropologist John Hawks recently got tenure, and blogged on it - go congratulate him!)
Dent, I’ve found you! - Alex references a hilarious cartoon depicting the 9 types of Principal Investigators.
Posted: 03 Aug 2008 02:23 AM CDT
Hello Health will change the way medicine is practiced worldwide. Believe me, that will happen. The service was just launched officially. And I can’t wait to see how it goes. What we can say at the moment is their marketing is perfect. How to create interactive ads? Like that:
Keep an eye on Jay Parkinson and Hello Health.
And if I can tell you a secret, I will launch something really new in this field in about 3 weeks… Stay tuned!
Posted: 03 Aug 2008 12:55 AM CDT
Now they have:
Unique idea on the life science market. You should definitely check it out.
Posted: 03 Aug 2008 12:46 AM CDT
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