Caught a great talk today at the OHRI by visiting speaker Mahendra S. Rao, who is probably the world's leading scientist in embryonic/neural stem cell therapies. The talk featured an overwhelmingly impressive wealth of data on neural stem cell biology, particularly pertaining to transplant studies. Most of this work was done in his former capacity as head of the NIH's stem cell program.What was most interesting about the talk was the work Rao is now leading as VP Stem Cell research at Invitrogen Corp (in the more ES-cell research friendly state of California). He recently took up this post after leaving the NIH as a result of their decision to abandon ES cell research in light of the Bush administration's strong anti ES cell research policies. From what he presented of his new project at Invitrogen, it's obvious they are now about to kick some serious ass in the arena of clinical therapeutic development. They've got GMP-friendly, FDA-approved and production-scalable technologies and ES cell lines ready to go. Couple with that Invitrogen's recent moves that has established the company as the leader in gene expression and cell culture technologies, and what you have is imminent domination of the biological therapies scene. Looks like one of the first applications they will go after is Parkinson's disease, using ES-derived neurons to replenish dopamine producers in the substantia nigra.
Interestingly, while transplanted ES-derived neurons are suitable for applications such as Parkinson's as they can survive long-term in recipient's brain, Rao mentioned that their potential in other regenerative therapies is limited by the fact that we do not yet know how to make the transplanted cells properly integrate into existing neuronal circuitry. Strong impetus for a lot of interesting research in probing neural connectivity...
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I'm not sure that it's even possible to get proper wiring. During development there are a lot of signals that direct the migration of neurons and the establishment of synapses. It's naive to think we can just put a cell in an adult brain and it'll just know what to do.
Yeah that's my thought too. However the developmental process might be less efficient than theoretical maximum, so you might be able to somehow get the neurons to the same endpoint in a useful timeframe through artificial manipulation. Then again, maybe you can beat development. Interesting question.
Then again, maybe you can't beat development was what I meant to say.
Actually there is a great essay on plos ONE about brain wiring:"Waddington referred to the buffering of developmental systems to produce a “wild-type” phenotype in the face of various mutations or environmental insults as “canalization” (though the definition of “wild-type” may be subjective—is right-handedness wild-type, for example?). Increasing mutational load should reduce the capacity for such buffering, leading to the prediction that individuals with greater developmental “noise” should be more susceptible to disease. Such noise can be indirectly measured by examining markers of “fluctuating asymmetry”, including fingerprint asymmetry, for example, which has indeed been found to be higher in individuals with schizophrenia."
That raises an interesting point regarding the genetics of noise buffering...this is in in the context of developmental noise. In another context, gene expression dynamic within cells has recently been shown to be very noisy, the source of this noise remain largely unknown. I've thought it would be interesting to know if there are particular genes within the cell that globally regulate the noisiness of gene expression. Some of these might also be genes that regulate the noisiness of development which goes can go awry and cause pathology as in the above example.
Here's an example: HSP90 reduces (buffers) global developmental/morphological "noise" in the fly and arabidopsis. However, this modeling study suggests that any gene that is part of a complex network can in theory act a global capacitator of phenotypes. Maybe it would be interesting to compare the relative contributions of each gene to the stability, robustness or noise of the genetic network of the cell as a whole...
Because evolution takes time, traits and molecular signatures must atleast partly represent capacities-noise? Since molecular capacities, even within a lifespan(ie developmental capacities) have the potential to cause disease when deregulated they are imp-no?!-so how do you study noise which accumulates over evolutionary time when you are trying to be a reductionist and can't even concentrate with the music on?!
Also an interesting point. I suppose the term noise is sort of a word borrowed from electronics which has only recently been applied to biology. In the context of telecommunications/electronics etc., it implies a sort of annoying uselessness. But as you point out what one would call "noise" in biology is perhaps actually equivalent to what we call the variation of biological traits, which may increase or decrease fitness depending on the environment. This variation is of course absolutely necessary for the evolution of life in the first place...
The way you talk about it Bayman, you seem to think noise is a purposeful regulated biological mechanism. I think rather it is just random, and a consequence of ineficiencies in biochemical reactions due to the second law of thermodynamics. I don't think transcriptional noise is engineered by the cell, it is just a consequence of pol ineficiency.The ineficiency of the polymerase is directed by natural selection, but there is a theoretical maximum.
Ahhh yes. Biology, the realm of purposeful randomness. Kind of like a good bayblab discussion.
Randomness with a purpose. A motto to live by.
Omar:
See Stephen Weber's hack at:
http://singpolyma.net/2006/10/comments-on-mainarchive-page-peek-boo/
Follow the instructions but ignore those pertaining to peek-a-boo functionality.
This will do the trick. If you find your page loads slow, you can copy the remotely hosted javascript file that is called in the first bit of javascript from http://jscripts.ning.com/get.php?xn_auth=no&id=2706908' type='text/javascript to your own host server and change the address line (script src=) to the url of the file at the new location.
Good luck!
Wrong again:
Try this - Comment hack
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