Fortunately, the field is rich in brilliant scientists thinking of ways to push the boundaries.

In a April 28, 2013 Chemical Biology paper a collaborative group of researchers in Slovenia and UCSF describe the rational design, production and characterization of a three-dimensional nanostructure folded out of a single peptide chain. What is most interesting is that this group strayed from the traditional path of peptide-based structure design. Normally, structural peptide design has been based on motifs and structures which are commonly found in natural proteins. De novo fold design and synthesis has been unsuccessful with the exception of a few cases.

Only when the structure is properly folded does the YFP assembly and display fluorescence. Image: Gradišar et al, Nature Chemical Biology 2013

The current report describes the application of a platform wherein interacting coiled-coil motifs drove the self-assembly of the protein fold. In this way, the group was able to design a tetrahedral structure which was very unlike protein folds found in nature. They went further and visually characterized their protein using AFM to directly see the small, three-dimensional, pyramid-like shapes. Additionally, they demonstrated the ability to functionalize these structures by attaching split pieces of the fluorescent protein YFP to different vertices of the tetrahedron  (shown above). One during proper folding would the YFP assembly correctly and show fluorescence. When the folding of the structure was disrupted, or if a position was deleted, the structure would align the segments of YFP and no fluorescence was be observed. While, this is a type of experiment which has been performed in other studies (i.e., the assembly of a Malachite Green RNA aptamer in RNA-based nanocube structures), it is an elegant and promising example of rationally designing peptide-based, non-natural structures.

The authors discuss the possibility of using these design principles for making nanostructures with cavities for drug delivery or for orienting synthetic catalytic sites. I’m excited to see what will come from subsequent studies, and also to see which biomolecule will be crowned king of the nanobiotech field – DNA? RNA? Protein?

References

1. Gradišar, H. et al. Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments. Nature chemical biology 1–6 (2013).doi:doi:10.1038/nchembio.1248

Happy DNA Day!

In honor of DNA Day, I wanted to share some of my favorite internet bits about DNA. Did I miss any of your favorites?

1. Visual representation of transcription and translation
PBS’ “DNA. The Secret of Life” is an extremely interesting feature focusing on this wonderful molecule. In the clip below we will see a remarkably accurate representation of the process of DNA transcription (the process of producing mRNA from DNA) and translation (the process of producing protein from mRNA) – in real time!

2. Francis Crick’s letter to his son shortly after discovering the structure of DNA
Reading this letter gives me chills every single time. Once Watson and Crick (with the aid of important discoveries and data collected by Rosalind Franklin and Maurice Wilkins) discovered the structure of DNA, they had a very short amount of time to publish it. There was a literal race to the finish in terms of getting the structure correctly. In fact, chemistry giant Linus Pauling (and twice Nobel laureate) tried to deduce the structure a bit too quickly and incorrectly imagined it as being a triple helix. Shortly after, Crick mailed his son Michael a letter describing in beautiful and elegantly simple terms and figures exactly what the discovery was and how important they felt it might be. Monumental is an understatement. You can read the letter at the New York Times.

3. The Nobel prize lectures of the co-discoverers of the DNA helix
While many believe that not all true contributors to the discovery of the structure of DNA were rightly credited, we shouldn’t discount the efforts of those who were. The awarding of the Nobel Prize in Physiology or Medicine in 1962 (less than a decade after the discovery) to Francis Crick, James Watson and Maurice Wilkins “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material” was a tremendous boon to biological research and the lectures given during the ceremony are worth a careful read. Click here to read Crick’s, Watson’s or Wilkins’ lectures.

4. Cold Spring Harbor Laboratory’s “DNA From the Beginning”
This is a great resource for those unfamiliar with the fundamental experiments leading to our understanding of the structure, function and use of DNA as well as those who just need a refresher. With useful animations, videos and clear text, this website delivers complex information in a nice, digestible package. Visit CSHL’s DNAftb now here.

5. Paul Rothemund: The astonishing promise of DNA folding (TED)
One of my favorite topics, bar none. DNA origami is a fascinating field in nanobiotechnology which attempts to use the base-pairing ability of DNA to form complex 3-dimensional structures with the hopes that they can be used as materials for nano-scale devices for use in applications such as computing and drug delivery. In this talk Paul Rothemund, one of the founding scientists of the field, discusses the promise of DNA origami, what has been achieved, and what he hopes for the future. (Though RNA is looking like an equally, if not more promising, addition to the playing field)

One of the most critical aspects of science is to record all important details of an experiment so that you, or anybody else, can repeat the methods that you performed to achieve the same results. Consistency is key! Unfortunately, if all of your methods are in your head or scribbled on scrap papers floating around the lab, you’ll have a hard time explaining to the new grad student taking over your project just how that blot turned out how it did.

When you join a lab you’re usually either given a lab notebook or are required to get one. If neither of these applies to you, then do yourself a favor and go get yourself a lab notebook. One without spirals, rings or perforate pages. A real lab notebook. Take your time in choosing it, too; you should love that thing.

Every page in your notebook should be used for something useful. Don’t print out a paper that you want to read and glue the pages of the paper into your notebook, it’s a waste of space on something that you can either keep in organized folders or, better yet, digitally (and yes, I know somebody who actually did glue articles into his notebook). Your notebook should be used for any combination of 3 things only: experiments, protocols and meeting notes.

Experiments

You may have learned in some of your lab classes that your pages should begin with a formal paragraph of experiment justification or purpose. This isn’t really the worst idea in the world to actually do, but it will grow tiresome very, very quickly. Usually, it’s enough to just write a sentence or two describing why you’re doing anything at the bench that day.

For example, “This is an analytical gel to determine if the replicate plate produced on 4/19/2013 (p. 145) contains positive clones of plasmid pET-28b(+).” There’s a lot of information in that one sentence! I didn’t need to describe that I did a transformation on competent cells to produce a plasmid which will be used for this and that. I know that I will be running an analytical agarose gel (meaning I’ll have sample left) on colonies grown on a plate with antibiotics for pET-28b(+) from transformants that I produced on a certain day with a note for page where the details of that day are held and where I can get the rest of the info for the experiment.

Protocols

Protocols are a little bit less critical than experiments to keep in your lab notebook. In fact, I have recently begun to keep a separate binder with a comprehensive set of personally optimized protocols and have moved this part of my life out of my lab notebook. However, if you don’t want to go through that effort, the lab notebook is still a great place.

Your protocols are your life, really. Well, your data is, technically – but without consistent and optimized protocols then good data will be few and far between. Having said that, you should keep a record of your protocol development in your notebook. Additionally, you should attach commercial protocols to your notebook with any modifications you make to them (e.g., different dilution volumes or cycling times, etc). You can be sure that if you lose your notes on protocol adjustments they won’t be on the new digital printout you get from the manufacturer’s website.

Meetings

This one I’m also on the fence about because I’ve moved away from this to a separate book as well, but I included it in my grouping since these are really the only three things which I believe are appropriate to keep in a notebook.

Meetings are a very important way to vet questions on difficult problems or to ascertain the direction of your lab group. However, without proper record of what goings-on in those meetings, you’ll likely forget about them in no time. Nobody wants an angry PI coming after you because you forgot about an action-item mentioned in a meeting, right? The solution is simple – write it down. The best part about keeping these things in a lab notebook are they are essentially permanent.

Don’t forget some of these other important suggestions:

• Glue is horrible. Get yourself some good tape, but use a generous amount. I do all four corners and all four sides.
• Initial across two edges of anything you tape into your notebook.
• Always use pen and make sure its black, unless changing the color is used for emphasis across all of your pages. Felt-tip or gel pens might bleed; stick with ballpoint.
• Don’t put sticky notes in your notebook; they’re itching the crawl away.
• Remember a good digital organization scheme is critical to organizing your data, and it can come in handy if you fall behind a few days in your lab notebook so that you only put accurate information in your record. I use a Main Folder > Data Folder > Date scheme labelled as Year_Month_Date for the date folder. This way I can organize my folders by name and pull up the most recent data very quickly. I also label my files with the same date-type scheme, for example “2013_04_19_HeLa_2uM-DAPI.tiff”. This also makes it really helpful if I need to email somebody a data file; the experimental details that are critical are in the file name so they can figure it out as well.
• The table of contents is your friend; use it. Yes, it’s a pain to fill out sometimes, but it’s helpful if you want to jump to a page during an in-person discussion or a meeting.

Remember that a clean, organized and complete lab notebook will save your behind someday. Don’t try and say that nobody ever told you so.

This poses an issue if you don’t want to be limited to services like LinkedIn, About.me or your university webpage for managing your online presence. Sometimes you want to display information that isn’t readily displayed by profile services because the fields simply don’t exist, such as funding awarded, selected publication, favorite links and methods or videos you love. There are a number of ways to produce a custom web presence (a WordPress blog, for example), but they are usually bloated with features that can take away from what you want to display, rather than enhance it.

To address this, I present to you SimpleCV – a clean, minimal and (best of all) free template for your online academic CV. 

It isn’t the fanciest thing you’ll find on the internet, but that’s the point. Your CV shouldn’t distract, it should focus, and the content to focus on here is you. What could be more important than you?! SimpleCV is exactly what it sounds like, a simple, clean and unobtrusive way to get what you want on the internet.

The best thing is you don’t need any web design experience to make SimpleCV work. You just need a text editor of some sort and a hosting space with a minuscule amount of space – no dynamic coding necessary! That means no databases, no php, etc. Some text editor options on Windows are TextPad or CrimsonEditor; on Mac try Fraise.

There are 2 files: a .html page that renders the CV and a placeholder .png for the profile picture. You can delete the profile picture if you want; it is provided as a demonstration of the size that fits nicely in the page.

Click the link below to download SimpleCV. You can change, use and share it however you’d like. No rights reserved! I put a small footer with a link back to this page in the code, but if you’re so inclined you may delete it.

If you’d like to help me and TheBioBlog in exchange for the download you can do a couple of things: (1) you can sign up for updates on the sidebar; (2) you can leave a comment below and tell me what you think or leave a link to your use of SimpleCV; (3) you can share this page on Facebook or Twitter; or (4) you can just tell people about the site.

Enjoy!

(8 kb / .zip file)

Check out the page now! https://www.facebook.com/TheBioBlog

Happy Monday!

I’ve been working on The Biology Blog over the past 4 years to bring you information on fresh, cutting-edge science. I’ve had some small hiatuses and lag between posts due to the rigor of graduate school and long hours in the lab. I’ve been working on new content that I hope to bring to you on a more regular schedule from now on, and I hope you’ll come back to see what I have to say and to let me know your opinions as well.

One of the first changes that I am making to streamline your reading experience at The Biology Blog is in email subscriptions. Previously, I used Feedburner to manage subscriptions to new posts. Subscriptions are now moving over to Jetpack (powered by WordPress.com), which I hope will be a more ideal option for getting notifications of new posts.

One of the drawbacks to this is the potential to leave current subscribers “behind,” so to say. Right now I’ve set a deadline of the end of June 2013 as a stopping point for collecting subscriptions on the site through Feedburner. The feeds will still be fed through Feedburner, but I will need to assess which option seems to be liked the most.

For now, I will suggest that everyone who would like to subscribe to please use the direct mail subscription, which is fed through Jetpack and WordPress.

Please keep an eye out for other changes.

More content this week!

Best,
JY

Update: Many thanks to Twitter user @MarcosEgeaCorti for a tip on a similar app for Android users, Colony Count. It’s in Beta right now, but it looks to be a pretty good alternative!

The iPhone is an incredible tool, but rarely have I seen it used for truly useful applications in the lab. Sure, there are molarity calculators and the like, but those can all be replaced by sitting at the computer and cranking out some numbers on the Google Chrome search bar (my favorite method). These sort of calculator-based Apps, while nice, don’t even come close to taking full advantage of the fact that the iPhone is a tool; it’s in your pocket almost constantly (those of us who have them), and is ready and waiting to be used! Don’t just use it as a calculator, it’s so much more.

A new tool was released today by Promega, a major player in the biotech research product field. The Promega Colony Counter ($3.99) is easily the best usage of the iPhone that I’ve seen to date.

Put simply, it’s an automated bacterial plate colony counter. All you have to do is take a picture of the plate and the App uses image segmentation algorithms to give a best guess for how many colonies are on the plate (presumably by simple size and shape measurements). Once the plate has been counted by the App, the user has the opportunity to refine the count by marking additionally colonies and masking areas that skew the obvious distribution (like satellite colonies, for example). What makes this App truly powerful, however, is the workflow. Setup a row of plates on your bench and go down the line, capturing images and calculating the colonies per plate; the App will organize them into a group and give you the averages across the set for reporting later or recounting if needed! All of this, in your hand and at your bench.

While the price may be steep for those who don’t usually like to buy the more “expensive” Apps, I feel like this tool is going to be seeing a lot of usage in bacteria-heavy operations. A cheaper alternative would be to take pictures and email them to yourself with your phone, then run them through a free segmentation software like CellProfiler.

With all of the benefits of this App, however, I can’t help but feel weird about using bacterial plates and holding your phone with the same hands… be careful!

While not quite as scientifically impacting (yet), Reddit user AllUpInHyuh posted images of a neuron model produced in the online game Minecraft - a game in which users interact to build, modify and interact in a world composed of Lego-like building blocks. The images show a structure composed of dynamic-type bricks which, in total, represent action potentials, ion fluxes and membrane boundaries of a neuron. As of this posting, a video of the model in action is unavailable.

This represents a very interesting perspective of biological modeling wherein users/researchers may actually “exist within” the systems they are modeling. Imaging following, real-time, an mRNA strand being produced, spliced, transported, translated and then degraded not by observing a rendering from a pre-made program, but by following a model produced by known physiological constraints of proteins, ions and other biomolecules involved. The possibilities are extremely exciting!

Click here to view the images of the Minecraft neuron model.

It turns out that the hypotheses, molecular modeling and in vitro biochemical tests were right – quadruplex DNA does exist! These motifs, termed G-quadruplex structures, are composed of guanine-rich sequences and exhibit a high thermodynamic stability and parallel-strand organization. Specifically, they “comprise two or more G-tetrads that form when four guanines  are held in a planar arrangement through Hoogsteen hydrogen  bonding, with additional stabilization provided by a monovalent cation coordinated to the O6 lone pairs of each guanine” (Source).

Presence of G-quadruplex DNA at various stages of the cell cycle. Biffi et al, 2013.

By using specifically engineered antibody approach to investigating these G-quadruplex structures in DNA, researchers at the University of Cambridge have provided the first quantitative evidence of their existence in vivo and further explored their role in genomic structure and organization.

It turns out that these structures are highly stable, and can be further stabilized by small molecule ligands. The additional observation that these structures are more numerous during cell division provides an interesting therapeutic opportunity; because pro-cancerous genes, or oncogenes, usually act to speed a cell through cell division, specifically targeting these G-quadruplex structures with a small molecule ligand might halt rapidly dividing cells and poise them for destruction.

Cancer biologists like to say that cancer cells “go or grow,” and that by halting their migration we can target specifically dividing cells. Discoveries such as those described in the Nature Chemistry paper published earlier today might provide some practical opportunities for taking advantage of this deadly behavior.

The researchers hope to further their investigation by structurally mapping the locations which are prone to developing these structures in order to gain insight into their physiological functionality at the genome-wide level.

This landmark discovery shifts our thinking by shattering the iconic image of DNA as only a double-helical structure and excites me about future discoveries fueled by this breakthrough.

Read more at PhysOrg and Nature.

References

• Biffi, G., Tannahill, D., McCafferty, J. & Balasubramanian, S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nature Chemistry 1–5 (2013).doi:10.1038/nchem.1548

My next tip I expect will be, for some, just as hard or harder to implement: I propose that by (1) being smart about intermediate steps in experiments and (2) reducing the amount of active work going on at the lab bench in any given moment you will experience the benefits of faster experiment times, less stress, and fewer mistakes caused by missteps and/or contamination. Essentially this means applying some principles of minimalism to your science.

One way that you might actively try to achieve minimalism in your science is to ask yourself questions will you’re writing out your volumes and pulling out your supplies: Can you reduce the number of tubes required for step 3 by using a master mix? Is it necessary to have your serological pipette controller sitting in the middle of your bench if you only need a 1 mL pipettor? Do you have to have to have four 200 uL tip boxes at your bench at all times? Why do you have three unused microfuge tube racks crowding your work area?

The number of questions to achieve a decluttered, blissful workspace is seemingly limitless.

If you have storage space, use it. If you don’t, go buy an art/tackle box to store things under your desk and bring them to the bench when you need them. I have an ArtBin Essentials 1-Tray (less than $20) for things that I don’t necessarily use at my bench but at instruments scattered around the lab; but why leave them by the instrument? They could get stolen, broken or generally get in the way of other people’s work. It’s easy to keep them in this convenient and inexpensive box and use them as needed. Plus, they’re not crowding the work area at my bench.

You clean your home; you clean your desk; why not keep your bench clean? You’ll feel more willing to get over to your bench and start your experiment if it’s clean, organized and inviting. Try to go in the opposite direction of the image below, I think you’ll be happier.

Happy New Year everyone! I wish everybody nothing but successful experiments in 2013!

As a little gift from me to you I’ve made a science-themed wallpaper (shown above and downloadable below). In the center are chromosome 20 and chromosome 13 (from an Alu FISH experiment uploaded to WikiDoc by C. Michael Gibson, MD), get it? 2013! There are two versions; one with an inspirational science quote by everyone’s favorite popularizer Carl Sagan, and one without the quote.

The wallpaper is freely downloadable below in a number of sizes to fit most popular resolutions:

Unless I make a change.

So for my first Grad School Zen tip, I say to get out of the bottomless pit of planning and just do your experiments. I’m not suggesting to do away with planning altogether, of course; planning is essential. I am suggesting to start being more active in going forth with experiments with the plan to be aware of challenges and mistakes, and to let those experiences inform repeats or future experiments.

I won’t wax poetic for too long on the point, because Leo over at ZenHabits has done a wonderful job on a related topic. Read his post “The Do Plan, or Why We Know But Don’t Do” for an excellent read on dropping the fear of accomplishing something and just doing it. I couldn’t help but be reminded how useful his tips were for life as a graduate student, and I hope to make the change from planning to doing right away. Productivity, here I come.

Rongxiang Xu is suing the Nobel Prize Assembly on allegations of overlooking his contributions to regenerative stem cell technologies

Rongxiang Xu, founder and chairman of MEBO International Group (a Chinese regenerative medicine company), filed a lawsuit in the Orange County, California court system this week against the Nobel Prize Assembly for allegedly overlooking his contributions when making the decision for the 2012 Nobel Prize in Medicine or Physiology. The prize was awarded to John Gurdon and Shinya Yamanaka “for the discovery that mature cells can be reprogrammed to become pluripotent.”

In Xu’s suit, which calls for a jury trial, he claims that his 1984 research demonstrated pluripotent reversion of stable somatic cells ahead of the research by Yamanaka and colleagues. His company markets a proprietary moist-exposed burn ointment (hence, MEBO) that boasts the ability to induce “physiological repair and regeneration of extensively wounded skin.”

While he claims earlier research, Xu’s patent (read the full text of US #6,991,813) for the product was filed in June 2001 and issued in January 2006; Yamanaka’s discoveries were submitted to the journal Cell in April 2006 and accepted in August 2006; the paper has been cited 4,265 times according to the Web of Science.

According to a statement by Dr. Xu, his “main priority for filing this suit was to clarify the Academy’s mistaken and misleading statements for the preservation of humanity and future generations, life science research should not desecrate the nature of human life” (PRNewswire).

The lawsuit (case number 30-2012-00615804-CU-DF-CJC) states that ”Dr. Xu has no interest in challenging the Nobel Prize, in discounting the work or discoveries of the scientists who won” and that his “main interest is in rehabilitating his dominant position as the owner, pioneer of the scientific achievement characterized in the publication at issue.”

Credit is extremely important in science, but when it comes to awarding it, what measure is most important? Who was first? Or who had the greatest impact. Arguably Dr. Xu’s patent has had a great impact on society, having been involved in the treatment of millions of patient in dozens of countries, but Yamanaka’s research has enabled thousands of scientists to make drastic discoveries in progressing the field. The results of this case will surely set new precedents for future decisions in awarding credit for seminal research.

Read more at Biotechniques, PRNewswire, and BioSpectrum.

The caption from their website:

On the cover: Nucleosomes serve as roadblocks to transcription, and in this issue, Bintu et al. (pp. 738–749) dissect these imposed barriers to rapid passage by eukaryotic RNA polymerase II (Pol II). Using single-molecule methods, they determine how the individual elements of the nucleosome—the histone tails, the specific histone-DNA contacts, and the DNA sequence—modulate the dynamics of transcription. The clay model on the cover illustrates how Pol II has to overcome two types of barriers during transcription through a nucleosome (blue): the histone tails at the entry site of the nucleosome (horizontal gate) and the histone-DNA contacts at the nucleosome dyad (stop sign). The secondary structure of the nascent RNA (pink) restricts backward movements of the polymerase during pauses, aiding transcription. Conceptual design by Lacramioara Bintu and Manchuta Dangkulwanich. Artwork by Manchuta Dangkulwanich and Gheorghe Chistol.

I highly recommend you do yourself a favor and check out some of their other gorgeous journal covers in the archives.

Other journals are trying to catch up, but Cell has really mastered the art of scientific journal covers. What are your favorite covers?

If the difference between N and N-1 ever matters to you, then you are probably up to no good anyway – e.g. trying to substantiate a questionable hypothesis with marginal data.

- W. H. Press et al., Numerical Recipes

Something to get you through your Friday – stay out of trouble with that data!

ORIGIN      
        1 ggggacaagt ttgtacaaaa aagcaggcta ggaggataac atatgacgca gatgaccgaa
       61 aacgatgaag aaccgattaa cactcacgaa ggtcgtatcc cgcaattcac gcacgagatg
      121 atcgactgga tcaacacgga gcgttgccaa ctggactcta ctgcgcgctc tagcgaaaac
      181 gacgcatctc cggcgcgtaa actgatcaac ggcctgatcg gtcatacggc cctgctggca
      241 cgcgaagcct ccctggaaga accgcagaat acgcacatct ctctgcaaaa cgagctgtat
      301 ttcgctcgca tgctggctac cgaaattaac acccatatct cttggatcaa taccgagcgt
      361 aacatcggcc atactaccca cgaaccggcc ctggagatgc agcagaacat ctctgcatgg
      421 gcgaacgatg agcgcgaacg ctctaaccag tggctgatcg aaagctggca tatcaccgaa
      481 cagaacccta ttaacgaggc aaatgacttc atccgttcta atcagtgggg tctgcaatgg
      541 agccagaacg cccgtcagca gtttacccag ccttctcatg ctaaggaaac tcacgaaacc
      601 cagatgactg aagccctgca aaatgaaatc tccgcgtggg ctaaagagtc cgaagcatcc
      661 cagaactctg gtcgtgaaga aaccattaac ggcagcttcc gtcagatgga caacgctacc
      721 tggcagcctc agattaatac ccagtgaacc cagctttctt gtacaaagtg gtcccc
//

Not so weird, right? Now, carefully look at the translation:

MTQMTENDEEPINTHEGRIPQFTHEMIDWINTERCQLDSTARSSENDASPARKLINGLIGHTALLAR
EASLEEPQNTHISLQNELYFARMLATEINTHISWINTERNIGHTTHEPALEMQQNISAWANDERERS
NQWLIESWHITEQNPINEANDFIRSNQWGLQWSQNARQQFTQPSHAKETHETQMTEALQNEISAWAK
ESEASQNSGREETINGSFRQMDNATWQPQINTQ

Are you seeing it yet? Let me help – trade out all of the letter Q appearances (Q = glutamine) for the letter O:

MTOMTENDEEPINTHEGRIPOFTHEMIDWINTERCOLDSTARSSENDASPARKLINGLIGHTALLAR
EASLEEPONTHISLONELYFARMLATEINTHISWINTERNIGHTTHEPALEMOONISAWANDERERS
NOWLIESWHITEONPINEANDFIRSNOWGLOWSONAROOFTOPSHAKETHETOMTEALONEISAWAK
ESEASONSGREETINGSFROMDNATWOPOINTO

And finally, add a few spaces and line breaks:

M TOMTEN
DEEP IN THE GRIP OF THE MIDWINTER COLD 
STARS SEND A SPARKLING LIGHT
ALL ARE ASLEEP ON THIS LONELY FARM
LATE IN THIS WINTER NIGHT
THE PALE MOON IS A WANDERER
SNOW LIES WHITE ON PINE AND FIR
SNOW GLOWS ON A ROOFTOP SHAKE
THE TOMTE ALONE IS AWAKE
SEASONS GREETINGS FROM DNA TWO POINT O

As is the tradition on the internet, a response has been issued – this time by the scientific news source Scientific American. In a post on her blog “Doing Good Science” entitled “On the apparent horrors of requiring high school students to take chemistry“ Janet Stemwedel, an Associate Professor of Philosophy at San Jose University, has provided potent rebuttals to Bernstein’s numerous, and often unsubstantiated, points.

I won’t go into it here, because this is already a blog post about a blog post about a blog post, but I will definitely urge you to visit the posts at the links above and read for yourself.

What do you think?

HEK-293 cells were used to synthetically design a two-communication system in mammalian cells. (Image: ATCC)

Published online in Nature Biotechnology last week, a multi-national team from Switzerland, Germany and France demonstrated the first example of rationally designed, two-way communication between mammalian cells (Source). While the microbiologist might scoff at this and point to any of the glut of literature describing synthetically design genetic circuits and phenotypic responses achieved in bacterial and yeast systems, the mammalian cell poses a significantly greater challenge. In the Letters publication, Bacchus et al. describe the engineering of “sender,” “processer” and “receiver” cells (all HEK-293 cells, a favorite for mammalian genetic engineers due to the ease of introducing foreign DNA) to exchange a variety of signaling molecules (including L-tryptophan, VEGF and acetaldehyde) in order to trigger specific, and pre-determined phenotypic responses.

This is huge.

This is the first time that mammalian cells have been rationally designed to mimic natural behavior in order to produce a specifically desired response. Even more impressively, they  didn’t leave their demonstration at just a simple signaling exchange – they showed a realistic, biologically relevant phenotypic response! The authors designed an experiment wherein a co-culture of cells designed to express and respond to different stimuli simulated the production and maturation of blood vessels. Using the vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), the authors observed that their system reproduced the characteristic transient permeability and tightening of endothelial layers which are critically important to the growth of blood vessels.

The authors emphasize the important point that, in contrast to bacteria and yeast, multicellular organisms are composed of specialized cell populations that tightly coordinate their physiology by intercellular communication. This article represents the first reverse-engineering of this intercellular communication, and in particular the first to reproduce a realistic biological phenomena. This development can provide two important opportunities for the research community: first, it can provide the tools to dissect important communication pathways and finely understand the nuances of these communications, much in the same way that recombinant DNA technology allowed us to do for gene networks; and second it provides the opportunity to design more biocompatible implants capable of communicating and interfacing with our natural physiology.

Catch the article in the link below!

References

• Bacchus, W. et al. Synthetic two-way communication between mammalian cells. Nature Biotechnology (2012).doi:10.1038/nbt.2351 (Source)