Thursday, October 1, 2009

“Noitulove”, one-Factor iPS cells and more in my picks of the week from RB

Another week has gone by and some very interesting molbio blog posts have been aggregated into Every week [see my opening post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.

Note that I'm only taking into consideration the molbio-related blog posts aggregated under "Biology".

Once again, three blog posts were selected this week:

1. Reverse evolution has been defined as the “reacquisition by derived populations of the same character states as those of ancestor populations” a

Can evolutionary changes be reversible? One could argue that the longer the “evolutionary path” (longer time span since diversifying from an ancestral state), the harder is to return to that specific ancestral state, due to accumulation of more changes.
Although there are many limitations to the study of reversibility, a recent paper argues that by “studying the reversibility of evolutionary changes in protein structure and function, (some of) these limitations can be overcome

Keith Robinson at Omics! Omics! discusses this paper which, by means of ancestral gene reconstruction, protein engineering and X-ray crystallography, uses the vertebrate glucocorticoid receptor as a case-study for reverse evolution. It appears that the path that led the ancestral gene to acquire its new functions it’s one that’s very hard to retrace directly. Several mutations which optimized the new specificity of the glucocorticoid receptor also destabilized elements of the protein structure that were required to support the ancestral conformation. So, reversing only the key function-switching mutations yields a non functional protein.

From the article:
Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution.
Keith states:
[T]his is a well-detailed case where evolutionary change eventually blocked the route back to the start.
a Teotónío AH & Rose MR (2001)Perspective: reverse evolution. Evolution 55: 653–660

2. A few weeks ago the Albert Lasker Basic Medical Research Award honored John Gurdon and Shinya Yamanaka

for discoveries concerning nuclear reprogramming, the process that instructs specialized adult cells to form early stem cells — creating the potential to become any type of mature cell for experimental or therapeutic purposes.
[See Quick post: Gurdon and Yamanaka win Lasker]

Yamanaka showed that you can generate pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions.
The study of these induced pluripotent stem cells (or iPS cells) has grown rapidly over the last few years: several studies have now reported the generation of iPS cells from human cells using the same factors.

Charles Daney over at Science and Reason discusses a recent article in Nature reporting the generation of iPS cells from human fetal neural stem cells using only one transcription factor: OCT4. Interestingly, these cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo.

Charles also comments on potential therapeutic applications of iPS cells and on a few issues that hamper their use at the time.

3. Structural genomics is the large-scale determination of protein structures. Cranial Discomfort discusses a provocative new article in Science reporting a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima, through the use of structural genomics and systems biology.
The network encompassed 478 proteins of which the structures of only 120 have been determined experimentally and 358 were predicted and modeled with a variety of computational approaches. This allowed for the generation of a metabolic model of T. maritima.

From the article:
(…) integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.

That's it for this week. Stay tuned for more MolBio Research Highlights!

ResearchBlogging.orgSome of the articles discussed in this week's selected posts:

Bridgham JT, Ortlund EA, & Thornton JW (2009). An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature, 461 (7263), 515-9 PMID: 19779450

Kim, J., Greber, B., Araúzo-Bravo, M., Meyer, J., Park, K., Zaehres, H., & Schöler, H. (2009). Direct reprogramming of human neural stem cells by OCT4 Nature, 461 (7264), 649-643 DOI: 10.1038/nature08436

Zhang Y, Thiele I, Weekes D, Li Z, Jaroszewski L, Ginalski K, Deacon AM, Wooley J, Lesley SA, Wilson IA, Palsson B, Osterman A, & Godzik A (2009). Three-dimensional structural view of the central metabolic network of Thermotoga maritima. Science (New York, N.Y.), 325 (5947), 1544-9 PMID: 19762644

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