Faculty of 1000

Post-publication peer review

Separation Anxiety

Posted by rpg on 4 March, 2010

Stem cells for dummies

The ability to maintain embryonic stem cell lines—more importantly, to preserve their pluripotence—in culture held out great promise for the treatment of a range of conditions from cancer to Parkinson’s disease. Unfortunately the technology ran into trouble when in 2001 the US Government restricted Federal funding to work done with the 21 lines that existed then, effectively kiboshing meaningful stem cell research in the US. Although the ability to induce pluripotency in adult cells (‘induced pluripotent stem’ or ‘iPS’ cells) avoided much of the controversy associated with deriving cells from human embryos, iPS cells are not as reliable as the real thing. All this changed last year when President Obama revoked the bill and enabled the development of new guidelines for Federal funding. And last month, the federal contract with the National Stem Cell Bank—the only one in the US—expired, throwing the stem cell game wide open.

All this means that we’re likely to see a lot more requests for stem cell line approval, like this:

Request for Human Embryonic Stem Cell
Line to be Approved for Use in NIH Funded Research. Type of Information
Collection Request: Revision, OMB 0925-0601, Expiration Date 02/28/
2010, Form Number: NIH 2890.

—and there’s even a Stem Cells for Dummies! (H/T)

Naturally, F1000 has its fair share of stem cell excitement. A study from Osaka University shows that embryonic stem cells do not have circadian rhythms; in fact, they do not express the transcriptional-translational feedback loops that generate rhythm in somatic cells. And although differentiation appears to induce circadian rhythm in these cells, subscequent treatment with the factors used to create iPS cells turns it off again. It’s not that straightforward though: an older paper, from Kyoto University, evaluated last week, finds a role for a cyclic gene that is expressed in stem cells, and in fact its expression level at the point of differentiation determines cell fate. So it would appear that circadian rhythm and commitment to cell differentiation are pretty much inseparable in development.

Six degrees of separation

It’s been an intriguing week for Structural Biology, too. The apparent similarity of many protein folds looks like an accident of physics rather than of evolution: there are only so many folds available to the 20 natural amino acids. Almost any two protein domains are separated by seven or fewer intermediate structurally similar domains—and this holds even for artificially-created polypeptide sequences.

The fact that evolutionary divergence need not be invoked to explain the continuous nature of protein structure space has implications for how the universe of protein structures might have originated, and how function should be transferred between proteins of similar structure.

Intrinsically unstructured proteins can lead to pathological conditions such as cancer and amylopathies. A paper from Madan Babu’s lab at the MRC-LMB (where I spent six happy years) shows that these proteins are actually very tightly and differentially regulated. Solving the three-dimensional shape of structured proteins, on the other hand, is fraught with difficulties. It’s exciting then to see a method that nearly doubles the size of proteins that potentially could be solved by NMR, by only looking at the peptide backbone assignments. Expect to see more NMR structures, and faster, then.

At the movies

I don’t think there’s any denying that studying the cytoskeleton gives the most opportunity for biology eye candy. A group at Southwestern Medical Center in Texas looked at how semaphorin receptors talk to the actin cytoskeleton, and show that fly cell ‘bristles’ reflect what’s going on inside the cell. They also show that a protein called Mical unbundles and depolymerizes actin fibres.

Finally, there’s been a lot of interest in how sticking cells down to a surface helps them stick mnore tightly to each other. A paper in the Journal of Cell Science, evaluated twice on F1000, describes an intriguing technique to test this: the researchers used two micropipettes to pull cells apart, measuring the force required as they do so. Reviewers Ekaterina Papusheva and Carl-Philipp Heisenberg say

In future studies, this could be used to visualize the spatial transmission of the signals between integrin and cadherin adhesion sites e.g. by implementing fluorescence resonance energy transfer biosensors

which should make for some very pretty data indeed. There is a movie of the technique, that I found fascinating. Can you predict when they’re finally going to separate?

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