Just a short post to share this hilarious video that I hope brings you and your mother closer this Mother’s Day – a little more than half of your DNA is thanks to them, you know!
A Biologist’s Mother’s Day Song
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Left Helix: Yellow! Rational design of single-chain peptide-based nanostructures
Nanobiotechnology is a rapidly growing and extremely fascinating field that, in one aspect, aims to rationally and selectively design biological molecules to perform advanced functions (the other aspect is to design non-biological platforms for biological processes). The most common biological molecules used are DNA, RNA and proteins for the reason that they may be conveniently and reliably produced by a variety of processes (PCR, IVT, IVTT, solid-state synthesis, etc). A few days ago I even mentioned one of these methods, DNA nanostructures (sometimes called DNA origami) and the amazing things they can do with biological computing. While there hasn’t been a world-changing breakthrough in the application of these structures yet, there has been some really interesting possibilities demonstrated. One of my favorites comes out of the institute I’m getting my PhD at and describes the application of DNA nanostructures as a platform for the directed assembly of synthetic vaccines.
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! 5 internet favorites to celebrate 60 years since the discovery of the structure of DNA
Happy DNA Day! On April 25th every year, we celebrate the 1953 publication of the discovery of the structure DNA in the journal Nature (Click here to read the paper!). 60 years is quite a short amount of time for us to have made such huge strides in understanding this exquisitely complex and exceedingly important biological polymer. All politics aside (we love you, Rosie!), the unbelievable environment of creativity and genius in the early 1950s was most definitely something to celebrate, and I hope you will!
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)
Grad School Zen #3: Use Your Notebook
Now’s as good a time as any to continue my Grad School Zen tips for us late night lab users looking to keep some peace and harmony in between the our PCR runs. My first two tips were to stop wasting time and do your experiments and to aim for minimalism. My third tip is one which I find I adhere to for pretty long stretches of time, but as soon as I drop out of habit with it, it’s time to play catch-up again – use your notebook!
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.
SimpleCV: A free, clean and minimal template for your online CV
While academics are expected to be highly skilled in a variety of fields, web design is not usually one of them.
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)