January 2011

NOTE: The MolBio blog carnival, referring to this edition, was the featured selection on blogcarnival.com for January 11, 2011.

Welcome to the latest edition of the MolBio blog carnival!

To those of you in the Northern Hemisphere, stuck in a cold winter, looking forward to summer, this picture I took in the mountains west of Tucson (Arizona) will hopefully bring you warm, happy memories. I love living in northern Colorado now, on the eastern edge of the Rocky Mountains, but I do at times miss living in Tucson.

Reading through the submitted science posts reminds me of how easy I had it, to some extent, as a graduate student in analytical chemistry. Much of my research involved sugar-binding proteins that would still work after I did horrible things to them.

Heat them at 37°C overnight, no problem. Stick them in DI water, they keep on binding.

Heat them at 37°C overnight in DI water, it's just another day in the life of a happy protein. Even the enzyme I studied retained considerable function when I smushed it onto a metal nanoparticle.

My postdoc took the gloves off by introducing me to a transmembrane protein involved in pain perception, a protein all too eager to stick its finger in my eye, unafraid to make clear that rough treatment is unacceptable. I'm happy in my cell membrane. I'm not going into your crappy surfactant-saturated vesicle membrane. Switch surfactants on me, will you? I'll just shoo away your drug molecule. That'll teach you a lesson, you worthless punk.

Anyway, the following are the posts received for this month:

Basics of Protein Phosphorylation Part IV: Taking it Off.
Christopher Dieni, writing in Bitesize Bio, continues a series on intracellular protein phosphorylation. How do enzymes that either add (kinases) or remove (phosphatase) phosphate units to/from a protein or proteins select their targets? How are the functional similarities and differences between kinases and phosphatases exploited to execute their complimentary functions? It's clear that these are complex questions; an introduction is provided in this blog post, along with some suggested reading. The entire series has been specifically noted by an editor at BiteSize Bio. Rosetta Web Servers.
Nir London, writing in the Macromolecular Modeling Blog, discusses extensions of Rosetta. Originally intended to predict macromolecular structure, it has been further developed to carry out many more useful functions. These include predicting changes in chemistry (e.g. conformational and binding properties) due to changing one amino acid unit, designing enzymes with new functions, and much more.

More MicroRNA Mysteries.
Becky Ward, writing in It Takes 30, discusses why RNA interference appears to be more effective against some targets than others. RNA interference may be especially useful for controlling gene expression (e.g. in cancer), but progress in this line of research is hampered by the fact that scientists have an insufficient understanding of how RNA interference works (with potentially fatal consequences). It turns out that presumed RNA interference efficacy may be dependent upon the rate of messenger RNA turnover. How Long is a Cell, and Why?
Another contribution from Becky Ward (It Takes 30) presents the finding that microtubules (directly or indirectly) in cells dictate cell length. Contrary to reasonable speculation, neither cell volume, shape, nor intracellular actin appears to be relevant. This was personally very interesting to me, since my graduate student research partially focused on using macromolecular crowding to control the shape of giant vesicles (yeah, I know, that's a long way from a living cell, and yeah, I know, I wasn't trying to control vesicle length). Becky's post was chosen as an editor's selection at researchblogging.org.

Current Trends in Cancer Stem Cells - Phenotypic Plasticity.
Alexey Bersenev, writing in Hematopoiesis, discusses how tumors progress on the biomolecular level; specifically, that the biochemistry of blood cancer cells is nonuniform and changes over time. If a specific biochemical signature is used to sort such cells for drug development, the drugs resulting from the subsequent studies may not effectively target the cancer. My presumption is that scientists must figure out which biochemical signatures are static and focus on those for drug discovery, or somehow use cellular heterogeneity to their advantage. The Knock-Out Punch: Zinc Finger Nucleases.
Kevin Bonham, writing in We Beasties, presents new developments aimed at quickly uncovering gene function in humans and other higher animals. In the past it has been very expensive and time-consuming to design a protein (e.g. a zinc-finger nuclease) that selectively targets and knocks out a human gene. Improved biomolecular design has now dramatically increased the number of genes that can be targeted in zebrafish with zinc-finger nucleases, with a vastly improved success rate. This development improves the prospects of zinc-finger nucleases for realistic use in human medicine.

Is It a Bird? Is It a Plane? No...It's Superantigens.
Faz, writing in Memoirs of a Defective Brain, discusses how the immune system recognizes bacterial invaders, and how bacteria can interfere with the immune response, with potentially lethal consequences. The awesome illustrative cartoons are reason enough to check it out. This topic is especially relevant to medicine today. I remember reading an article in Nature a few years ago about an experimental drug intended to interfere in the immune response, that ended up almost killing the patients by causing an extreme systemic reaction. Bacterial Biofilms that Broadly Resist Liquids and Gases.
Before parting, I'm going to torture you with a blog post by yours truly, written up in Phased. Most microbiologists know of bacterial biofilms, and the havoc they can cause in human medicine. It turns out that they can be far more resilient to chemical attack than is commonly appreciated; the fundamental, specific biochemical and physical basis of this resilience is only now being unraveled. Impressive biofilm resilience (at least one bacterial species briefly repels drain opener, which I presume is roughly 50% sodium hydroxide) may be bad news for drug development, but it's possibly very good news for the design of cheap, renewable, broadly-useful nonwetting surfaces.

That's it for this month's edition of The MolBio Carnival. You can check future hosts and past editions on the Carnival's home page. Be sure to subscribe to the RSS feed to receive notifications and summaries when new editions of the Carnival are posted. Also, you are welcomed to submit your best molbio blog articles to the next edition of The MolBio Carnival which will be hosted at MolBio Research Highlights. More info about the Carnival here.

This isn't blogger, wordpress, or anything like that, so I don't have a comment function. Nevertheless, if you do feel so inclined, I'd like to hear from you (you did a good job, you did a crappy job, a scientific correction, reporting a nonfunctional link, whatever). Drop me a line:
mslong79 at gmail dot com

Lauck, F., Smith, C., Friedland, G., Humphris, E., & Kortemme, T. (2010). RosettaBackrub--a web server for flexible backbone protein structure modeling and design. Nucleic Acids Research, 38 (Web Server) DOI: 10.1093/nar/gkq369

Larsson E, Sander C, & Marks D (2010). mRNA turnover rate limits siRNA and microRNA efficacy. Molecular Systems Biology, 6. PMID: 21081925

Takaku Y, Shimizu H, & Fujisawa T (2010). Microtubules are involved in regulating body length in hydra. Developmental Biology. PMID: 21047507

Picone R, Ren X, Ivanovitch KD, Clarke JD, McKendry RA, & Baum B (2010). A polarised population of dynamic microtubules mediates homeostatic length control in animal cells. PLoS Biology, 8 (11) PMID: 21103410

Sander, J., Dahlborg, E., Goodwin, M., Cade, L., Zhang, F., Cifuentes, D., Curtin, S., Blackburn, J., Thibodeau-Beganny, S., Qi, Y., Pierick, C., Hoffman, E., Maeder, M., Khayter, C., Reyon, D., Dobbs, D., Langenau, D., Stupar, R., Giraldez, A., Voytas, D., Peterson, R., Yeh, J., & Joung, J. (2010). Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nature Methods, 8 (1), 67-69. DOI: 10.1038/nmeth.1542

Doyon, Y., Vo, T., Mendel, M., Greenberg, S., Wang, J., Xia, D., Miller, J., Urnov, F., Gregory, P., & Holmes, M. (2010). Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nature Methods, 8 (1), 74-79. DOI: 10.1038/nmeth.1539

Fraser, J., & Proft, T. (2008). The bacterial superantigen and superantigen-like proteins. Immunological Reviews, 225 (1), 226-243. DOI: 10.1111/j.1600-065X.2008.00681.x

Epstein, A., Pokroy, B., Seminara, A., & Aizenberg, J. (2010). Bacterial biofilm shows persistent resistance to liquid wetting and gas penetration. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1011033108

Basics of Protein Phosphorylation Part IV: Taking it Off. Christopher Dieni, writing in Bitesize Bio, continues a series on intracellular protein phosphorylation. How do enzymes that either add (kinases) or remove (phosphatase) phosphate units to/from a protein or proteins select their targets? How are the functional similarities and differences between kinases and phosphatases exploited to execute their complimentary functions? It's clear that these are complex questions; an introduction is provided in this blog post, along with some suggested reading. The entire series has been specifically noted by an editor at BiteSize Bio.	Rosetta Web Servers. Nir London, writing in the Macromolecular Modeling Blog, discusses extensions of Rosetta. Originally intended to predict macromolecular structure, it has been further developed to carry out many more useful functions. These include predicting changes in chemistry (e.g. conformational and binding properties) due to changing one amino acid unit, designing enzymes with new functions, and much more.
More MicroRNA Mysteries. Becky Ward, writing in It Takes 30, discusses why RNA interference appears to be more effective against some targets than others. RNA interference may be especially useful for controlling gene expression (e.g. in cancer), but progress in this line of research is hampered by the fact that scientists have an insufficient understanding of how RNA interference works (with potentially fatal consequences). It turns out that presumed RNA interference efficacy may be dependent upon the rate of messenger RNA turnover.	How Long is a Cell, and Why? Another contribution from Becky Ward (It Takes 30) presents the finding that microtubules (directly or indirectly) in cells dictate cell length. Contrary to reasonable speculation, neither cell volume, shape, nor intracellular actin appears to be relevant. This was personally very interesting to me, since my graduate student research partially focused on using macromolecular crowding to control the shape of giant vesicles (yeah, I know, that's a long way from a living cell, and yeah, I know, I wasn't trying to control vesicle length). Becky's post was chosen as an editor's selection at researchblogging.org.
Current Trends in Cancer Stem Cells - Phenotypic Plasticity. Alexey Bersenev, writing in Hematopoiesis, discusses how tumors progress on the biomolecular level; specifically, that the biochemistry of blood cancer cells is nonuniform and changes over time. If a specific biochemical signature is used to sort such cells for drug development, the drugs resulting from the subsequent studies may not effectively target the cancer. My presumption is that scientists must figure out which biochemical signatures are static and focus on those for drug discovery, or somehow use cellular heterogeneity to their advantage.	The Knock-Out Punch: Zinc Finger Nucleases. Kevin Bonham, writing in We Beasties, presents new developments aimed at quickly uncovering gene function in humans and other higher animals. In the past it has been very expensive and time-consuming to design a protein (e.g. a zinc-finger nuclease) that selectively targets and knocks out a human gene. Improved biomolecular design has now dramatically increased the number of genes that can be targeted in zebrafish with zinc-finger nucleases, with a vastly improved success rate. This development improves the prospects of zinc-finger nucleases for realistic use in human medicine.
Is It a Bird? Is It a Plane? No...It's Superantigens. Faz, writing in Memoirs of a Defective Brain, discusses how the immune system recognizes bacterial invaders, and how bacteria can interfere with the immune response, with potentially lethal consequences. The awesome illustrative cartoons are reason enough to check it out. This topic is especially relevant to medicine today. I remember reading an article in Nature a few years ago about an experimental drug intended to interfere in the immune response, that ended up almost killing the patients by causing an extreme systemic reaction.	Bacterial Biofilms that Broadly Resist Liquids and Gases. Before parting, I'm going to torture you with a blog post by yours truly, written up in Phased. Most microbiologists know of bacterial biofilms, and the havoc they can cause in human medicine. It turns out that they can be far more resilient to chemical attack than is commonly appreciated; the fundamental, specific biochemical and physical basis of this resilience is only now being unraveled. Impressive biofilm resilience (at least one bacterial species briefly repels drain opener, which I presume is roughly 50% sodium hydroxide) may be bad news for drug development, but it's possibly very good news for the design of cheap, renewable, broadly-useful nonwetting surfaces.