Paper of the Week at JBC

A stalled ribosome (Dark Blue) is rescued through translation of the tmRNA ORF (Magenta). Proper positioning of this region of tmRNA in the A-site is achieved by the C-terminal tail of SmpB (Yellow) which is connected to the body of the SmpB protein (Orange) by a flexible glycine residue (Yellow gymnast). Generated with PDB files 4ABR, 4ABS, and 3J18.

Although I usually don't use this blog to herald my own accomplishments (i.e. I didn't mention successfully earning my doctorate earlier in the year), I cannot hide my excitement that my first author article, "Active and Accurate trans-Translation Requires Distinct Determinants in the C-terminal Tail of SmpB Protein and the mRNA-like Domain of Transfer Messenger RNA (tmRNA)", has been selected for paper of the week.

As a paper of the week (an honor bestowed on less than 5% of all JBC articles, I am told), there is a neat summary of the article on the JBC site. The summary / synopsis piece is entitled "How Two Molecules Keep Ribosomes Moving". Along with this preview, there is also short profile about me.

Unfortunately, reading the actual, finished article requires a subscription to the Journal of Biological Chemistry. A word of caution to interested readers: it is written for an expert scientific audience (as almost all research articles for scientific journals are). However, it is possible to view the earlier, 'online' version of the article; in addition, the JBC capsule provides a bite-sized summary of the work.

The below is copied from the article page at the JBC website. Although I wrote most of it, I claim no copyright. You can find the original text at http://www.jbc.org/content/early/2013/08/28/jbc.M113.503896

Capsule

Background: tmRNA and small protein B (SmpB) rescue stalled ribosomes through a template switching mechanism.

Results: Changes to the SmpB hinge, SmpB C-terminus, or tmRNA ORF affect ribosome rescue activity and accuracy.

Conclusion: Proper positioning of SmpB and tmRNA make distinct and supplementary contributions to ribosome rescue.

Significance: Template switching requires concerted action of distinct SmpB, tmRNA, and ribosomal determinants.

A Blogroll for Synthetic Biology

The emerging discipline of synthetic biology holds tremendous potential for both basic research and for delivering powerful, novel solutions to real world problems (both in medicine and in other industries). This field has grown from a handful of researchers at Princeton, MIT, Harvard, and Universities in California (with pioneers such as Dr. Drew Endy, Dr. George Church and Dr. Ron Weiss leading the way) to include laboratories all over the world. It is my belief that this field will represent the future of biology and will be a vast and critical part of the economy in the years to come.

There are several great resources on the web to learn about synthetic biology and keep abreast of the latest developments. In addition to sites such as syntheticbiology.org, I present below a blogroll of great sites to visit for anybody interested in this amazing field. (Image above is modified from synthetic biology.org; I claim no rights to this image). Of course, I haven't included my own blog, even thought I already have several posts about synthetic biology (for example, my article about DNA synthesis)

My Top Three:

Oscillator

http://blogs.scientificamerican.com/oscillator/

Part of the scientific american family of blogs, Oscillator mostly focuses on Synthetic Biology and is a great resource for interesting articles and news about the field. I especially like some of the perspectives given by the main author Chistina Agapakis (whom you can follow on Twitter).

Peccoud Lab Journal Club Page
http://peccoud.vbi.vt.edu

http://peccoud.vbi.vt.edu/category/journal-club/

For the aficionado or seasoned expert, this is a great resource where recent papers about, or related to, synthetic biology are discussed. This is a great feature to have on a laboratory group website which deserves emulation by other scientists.

Dreamer Biologist's Blog

http://dreamerbiologist.wordpress.com/blog-2/

This blog, maintained by an undergraduate with a passion for biology (and synthetic biology in particular), features articles on a range of topics. He maintains a separate section with material solely devoted to synthetic biology (http://dreamerbiologist.wordpress.com/synbio/), and the title of the biology I think captures the essence of what this field is: a call for biologists to dream up novel solutions to real world problems, and imagine new technologies based upon the power of life.

Please continue reading the article to get my full list of synthetic biology blogs and sites (Click 'Read More'). They are really worth a read! 

Do you know of a blog or site that I have missed? Please share the link and a description below by leaving a comment.

E. coli Biosensors: Going for the Gold

All that glitters is not gold, and the shine of most modern gold deposits are hidden underneath layers of dirt, soil and sand. Finding these deposits usually requires expensive and time-consuming chemical analysis of soil samples. Recently, an international team of reseachers met this challenge of gold exploration and prospecting by turning a common gut microbe, Escherichia coli (E. coli), into a miniature gold detection device.

In a recent paper published in PLoS One, researchers from the University of Nebraska and their collaborators in Australia detail how they have genetically modified E. coli to act as a gold biosensor by borrowing the golTSB genes from a closely related microbe, Salmonella typhimurium. By pairing these gold recognition genes to a known enzymatic activity, researchers can detect and quantify small amounts of gold by simply measuring a change in the color of the bacteria-containing solution. The gold detection limit for this biosensor is on par with that of the chemical analysis currently used in the industry, which is slower and involves much more expensive instruments.

These proof-of-concept studies, which were partly funded by both Newmont Exploration Proprietary Limited and Barrick Gold of Australia Limited, are the latest step towards the development of a quick, accurate and specific biosensor that will make examining potential gold mining sites easier and faster. The authors of the study demonstrate that their biosensor can be used to determine the concentration of gold in a soil sample or a sample containing multiple metals. This is an improvement over earlier research of prototype biosensors, which only demonstrated detection in relatively pure samples.

For more detail and commentary about this study, please select 'Read More'. Do you think cell based biosensors will revolutionize gold exploration? Comments are welcome below!

Nanopore Sequencing: Towards Reading and Writing?

Nanopore sequencing is an emerging technology that promises fast, easy and affordable way to 'read' the bases in DNA. While researchers are seeking the $1000 genome, nanopore sequencing (once refined) may be able to deliver under budget and on a time scale of minutes, not hours or days.

Other bloggers and science writers (at BiteSize Bio, among others) have done a great job covering this technology (several of which I complied at the end of this article in a short 'webibliography', or bibliography of websites). Here, I would like to speculate on the use of a nanopore for the synthesis (or writing) of a DNA sequence. 

FInding a cheaper and faster way to synthesize a DNA sequence is a big challenge, and one that with a growing urgency. I've previously highlighted the importance of meeting this challenge and some current attempts at solutions. The ideal solution may currently be residing in the realm of science fiction. As I mentioned in the previous article, solutions that employ a controllable polymerase have great potential. A recent article from the Akeson laboratory (Olasagasti, 2012; PMC3711841) shows that this may be possible. Indeed, Akeson and colleages are able to electronically control both the threading of DNA through a nanopore, as well as the synthesis of the threaded DNA. 

Select 'Read More' to see the rest of the article. What are your thoughts on nanopore sequencing? Do you think that it is feasible that this technology can be adapted in some way for a next-generation DNA sequencing solution?

A Webibliography of Microbiology Blogs

There are many places on the web to read about microbiology and molecular biology. From science news breaks to commentary on research and everything in between, below are my favorite blogs and sites devoted to the field (other than my own, of course). This list is often referred to as a blogroll, although here I am calling it a webibliography (a condensed version of the phrase used by a friend and fellow blogger, Michael Goeller, at the Kenilworthian).

My Top 5 Greatest Hits (with a bullet!)

Microbe World: A terrific hub for everything microbiology. This site contains blogs and news feeds, as well as excellent podcasts such as TWiM (This Week in Microbiology). Sister podcasts include the more specific TWiV and TWiP (This Week in Virology and Parasites, respectively).

MicroBEnet: A great blog, which I have included in this greatest hits collection for the reason given in the note below. This blog focuses on various aspects of microbiology, with a particular focus on those microbes that share our dwellings (the microbiology of the built environment, as the author himself describes it.) This focus is connected with a program setup by the Sloan Foundation.

Of particular interest in the MicroBEnet blog is the Microbiology Blogroll post, which is similar to the very collection of websites you are currently reading. The blogroll post is much more comprehensive than my own list (although it lacks the CSHL blog), although it is unannotated. Instead, the most recent post for each blog is shown.

Small Things Considered: This blog, which seems to have a title that plays off of an NPR game show, is an excellent read. It is supported by the American Society for Microbiology (ASM). Here you can find microbiology news ranging from the TWiM press family, as well as reviews and commentary on primary literature (look for the research blogging icon) and everything in between. 

Research Blogging, Biology: A sort of biology blog aggregation site which lists posts from a variety of authors and topics with a common thread: they all are either review or commentary on primary research. You may have noticed the research blogging icon on other sites; all of these posts are also listed at this website. 

CSHL Lab Dish:  A news blog for Cold Spring Harbor Laboratory, a preeminent research organization (can be considered the birthplace of molecular biology). Although infrequently updated, the quality posts are worth the wait. My favorite are the SCIENCE SHORTS: brief and straightforward 5 minute talks on a particular topic, prepared for a general audience.

Select 'Read More' to see the rest of my annotated list of microbiology websites. Do you have a favorite site that I have missed? Please feel free to share it by leaving a comment below!

NusA to save the day during heat shock: commentary and review of Li, et al 2013

A review of Li, et al Escherichia coli transcription termination factor NusA: heat-induced oligomerization and chaperone activity (2013) Scientific Reports, vol 3 (2347) PMCID: PMC3731644

In previous blog posts, I have taken a look at two slightly dated articles concerning drug development against mycobacterium tuberculosis. Here I will continue my series of reviews but with a new direction. My last review provided a new perspective on a study that had already received press from others. For this review, I have chosen a much more recent paper, which has not been analyzed (to my knowledge) by another other blogger, science journalist, or microbiology enthusiast.

Why have I chosen a paper on NusA molecular biology in E. coli? Other than the fact that the article is fresh off the press (from the Nature sub-journal Scientific Reports), the claims (which are fairly well supported) the authors make are another example of how bacterial proteins often function as swiss army knifes: they have multiple functions, sometimes not revealed until environmental conditions are changed or cellular stresses are introduced. 

I will begin this review with a short summary, known as a Capsule. This style of synopsis / abstract is being pioneered by the Journal for Biological Chemistry (JBC), and I think it is a great idea for making summaries primary research literature more accessible to a general audience. One way to think of it is a shorter abstract, written not for experts but for the public (and policy makers, I suppose!). Authors of manuscripts submitted to JBC must provide a capsule statement; here, the capsule below is my own, not written by the authors of the NusA study in Scientific Reports (and not conforming to JBC's strict 60 word limit).

Capsule

Background:  NusA is a protein factor known to be involved in transcription termination and anti-termination (transcription is part of the process of turning genetic information in DNA into proteins and enzymes).

Results: Upon heat shock, NusA forms oligomers (multiple copies of the same protein factor bound together) which help prevent other proteins from aggregating.  

Conclusion: NusA contributes to the heat-shock resistance in E. coli by acting as a buffer to protein aggregation.

Significance: Describes a new role for NusA and expands the knowledge of how bacteria cope with stress; these abilities (in general) are important for many bacteria, including pathogenic bacteria that must resist stress from our immune system and medicines.

I invite readers to form their own capsule of this article, especially if you disagree with my choice of areas to emphasis.

Manuscript Highlights

1. NusA is the latest example of a multi-functional protein with latent chaperone 'buffer' activity during heat-shock. GreA, another transcription related factor, is also recent example.

2. NusA oligomerization (distinct from aggregation), mediated by the C-terminal repeat domains, is thought to be responsible for the chaperone buffer activity.

3. NusA's role in heat-shock conditions is not demonstrated under physiological conditions; experiments are done in vitro or with over-expressed and tagged NusA. This may reflect technical limitations.

Select 'Read More' to see the rest of the review

Protein Folding can be fun in more ways than one

Although this blog often features serious discussions of scientific research, I am myself a big fan of board and card games. In fact, I am an avid chess player, dedicated enough to play in (and sometimes place) in tournaments in the New York area. I even run another blog devoted to Chess and the ways in which it intersects with Science.

One feature of gameplay that attracts me is how it can be adapted for educational uses. In indirect and abstract ways Chess has taught me a multitude of lessons. Other games, such as Scrabble and Boggle (and some iPhone adaptions or derivatives) may help to improve one's vocabulary, even if just slightly. More to the point, however, I recently began to think of ways to devise some games that will make certain concepts in Microbiology and Molecular Biology easier to grasp and fun to learn.

Here I am showcasing the first of these efforts: a game about protein folding. Protein folding describes the manner in which a protein, which is a polymer (or string) of amino acids in a particular sequence, folds into a 3-dimensional shape. For a refresher on the relationship between our genetic material and a protein's shape, please refer to my crash course on the central dogma of molecular biology. The 3D configuration of a protein is extremely important in microbiology and molecular biology. A majority of the behaviors a microbe carries out are executed by proteins, and protein structure usually dictates function.

Before giving you a description of my invention, which is meant solely for edutainment, I need to point out another game that revolves around protein folding. FoldIt, designed by David Baker's laboratory group, is at once an entertaining computer game and a brilliant idea. Since it is difficult for computers to accurately determine the structure of a protein from the amino acid sequence alone, Baker uses FoldIt to enlist the help of people all across the world in this task. By taking protein structures and turning them into puzzles, FoldIt has players tweak the shapes of proteins and rewards them with points for more stable structures. Apart from actually being quite fun (especially if you are a fan of puzzle games), playing this game actually advances scientific research and protein structure prediction.

My game, which I tentatively call "Protein Power" (for lack of a better name), is different. It is a board game designed simply for fun and to teach some concepts behind protein folding. It resembles in some ways both Scrabble and primitive protein folding models (ones in which polar and hydrophobic beads were placed upon a grid). The screen shot above gives you a glimpse into the game: you place amino acid tiles upon a board and score points for connections or interactions between them: hydrophobic interactions are rewarded, salt bridges score points as well. Hopefully, through the game players will become familiar with the idea that protein folding involves hiding hydrophobic residues from water and forming energetically stable structures. At the very least, I hope they have fun playing and that the gameplay is not too derivative (I think it's actually fairly original). Unlike Foldit, it is a multiplayer, strategic board game.

Select 'Read More' to see the rules for the game and example gameplay.