Biomolecule Imaging Pioneers Share Nobel Prize

Today, the Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2017 to Jacques Dubochet (University of Lausanne, Switzerland) and Joachim Frank (Columbia University, New York, USA), and Richard Henderson (MRC Laboratory of Molecular Biology, Cambridge, UK). The award is given "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution"

Cool microscope technology revolutionises biochemistry

We may soon have detailed images of life’s complex machineries in atomic resolution. The Nobel Prize in Chemistry 2017 is awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for the development of cryo-electron microscopy, which both simplifies and improves the imaging of biomolecules. This method has moved biochemistry into a new era.

A picture is a key to understanding. Scientific breakthroughs often build upon the successful visualization of objects invisible to the human eye. However, biochemical maps have long been filled with blank spaces because the available technology has had difficulty generating images of much of life’s molecular machinery. Cryo-electron microscopy changes all of this. Researchers can now freeze biomolecules mid-movement and visualize processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.

Electron microscopes were long believed to only be suitable for imaging dead matter, because the powerful electron beam destroys biological material. But in 1990, Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Joachim Frank made the technology generally applicable. Between 1975 and 1986 he developed an image processing method in which the electron microscope’s fuzzy two-dimensional images are analysed and merged to reveal a sharp three-dimensional structure.

Jacques Dubochet added water to electron microscopy. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse. In the early 1980s, Dubochet succeeded in vitrifying water – he cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimised. The desired atomic resolution was reached in 2013, and researchers can now routinely produce three-dimensional structures of biomolecules. In the past few years, scientific literature has been filled with images of everything from proteins that cause antibiotic resistance, to the surface of the Zika virus. Biochemistry is now facing an explosive development and is all set for an exciting future.

About the Nobel Laureates

Jacques Dubochet, born 1942 in Aigle, Switzerland. Ph.D. 1973, University of Geneva and University of Basel, Switzerland. Honorary Professor of Biophysics, University of Lausanne, Switzerland.
www.unil.ch/dee/en/home/menuinst/people/honorary-professors/prof-jacques-dubochet.html

Joachim Frank, born 1940 in Siegen, Germany. Ph.D. 1970, Technical University of Munich, Germany. Professor of Biochemistry and Molecular Biophysics and of Biological Sciences, Columbia University, New York, USA.
http://franklab.cpmc.columbia.edu/franklab/

Richard Henderson, born 1945 in Edinburgh, Scotland. Ph.D. 1969, Cambridge University, UK. Programme Leader, MRC Laboratory of Molecular Biology, Cambridge, UK.
www2.mrc-lmb.cam.ac.uk/groups/rh15/

What can we use from this in teaching undergraduate A&P?

• If you talk about imaging molecules in your course, this could be a way to garner student interest—considering that this is a current and ongoing effort in science. I always have a brief "shape is important in biological chemistry and here's what we can see with current tools" because they're going to see all those little odd-shaped rutabaga blobs in illustrations in their textbooks.


• If you bring up microscopy in your course, perhaps describing the types of microscopy, adding a bit of info on this could help show students that microscopy is still evolving—in exciting ways.


• Consider using the annual Nobel Prize announcements as a springboard to discuss the process of scientific discovery. 


• Consider mentioning the other major awards for scientific achievement and discuss what the judges seem to value most about scientific discoveries. The Nobel Prize is the one everyone has heard of, so it's a great place to start.


• Use the Nobel Prizes (and other awards) over time as a way to keep students aware of the history of, and progress, of human biology. One could also address the global diversity of laureates.  Or the lack of other kinds of diversity among laureates.

Want to know more?

Popular Information 

• my-ap.us/2hNGb1D 

Scientific Background

• my-ap.us/2hPtKm0

Images

Image - 3D structures (pdf 1.4 MB)

• © Johan Jarnestad/The Royal Swedish Academy of Sciences
• my-ap.us/2hNUq6o

Image - Blobology (pdf 8.5 MB)

• © Martin Högbom/The Royal Swedish Academy of Sciences
• my-ap.us/2hLMaDV

Image - Dubochet's preparation method (948 kB)

• © Johan Jarnestad/The Royal Swedish Academy of Sciences 
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Image - Frank's image analysis (pdf 1 MB)

• © Johan Jarnestad/The Royal Swedish Academy of Sciences
• my-ap.us/2hMkU8i 

Cool Animations (literally)

Structure and gating of the nuclear pore complex

• Eibauer M, Pellanda M, Turgay Y, Dubrovsky A, Wild A, Medalia 
• my-ap.us/2hMolMe
• my-ap.us/2hKWxbd

Ion gating in the sarcoplasmic reticulum membrane

• Samsó M, Feng W, Pessah I, Allen P
• my-ap.us/2hLJCWg

Antibody structure

• Zhang L, Ren G
• my-ap.us/2hLQp2j

Native LDL particles

• Kumar V, Butcher S, Öörni K, Engelhardt P, Heikkonen J, Kaski K, Ala-Korpela M, Kovanen P
• my-ap.us/2hO4Qms

Changes in the water and ion contents of organelles during apoptosis

• Nolin F, Michel J, Wortham L, Tchelidze P, Banchet V, Lalun N, Terryn C, Ploton D
• my-ap.us/2hMTYW4

Adapted from press release at nobelprize.org
Click each image for its source/attribution

Dissolving Microneedle Vaccinations

Researchers recently demonstrated that a flu vaccine delivered using microneedles that dissolve in the skin can protect people against infection even better than the standard needle-delivered vaccine.

The new microneedle patch is made of dissolvable material, eliminating needle-related risks. Not to mention the sea change it may mean for patients with severe needle anxiety!  I suspect this approach may also be more tolerable for many patients than oral and nasal vaccination methods. It is also easy to use without the need for trained medical personnel—making it ideal for use where healthcare resources are limited.

“Our novel transcutaneous vaccination using a dissolving microneedle patch is the only application vaccination system that is readily adaptable for widespread practical use,” said Professor Shinsaku Nakagawa, one of the authors of the study from Osaka University. “Because the new patch is so easy to use, we believe it will be particularly effective in supporting vaccination in developing countries.”

The new microneedle patch – MicroHyala – is dissolvable in water. The tiny needles are made of hyaluronic acid, a naturally occurring substance in tissue matrix and the synovial fluid that cushions the joints. When the patch is applied sort of like a Band-Aid, the needles pierce the epidermis of skin and dissolve into the body, taking the vaccine with them.

The researchers compared the new system to traditional needle delivery by vaccinating two groups of people against three strains of influenza: A/H1N1, A/H3N2 and B. None of the subjects had a bad reaction to the vaccine, showing that it is safe to use in humans. The patch was also effective: people given the vaccine using the microneedles had an immune reaction that was equal to or stronger than those given the vaccine by injection.

“We were excited to see that our new microneedle patch is just as effective as the needle-delivered flu vaccines, and in some cases even more effective,” said Professor Nakagawa.

Previous research has evaluated the use of microneedles made of silicon or metal, but they were not shown to be safe. Microneedles made from these materials also run the risk of breaking off in the skin, leaving tiny fragments behind. The new dissolvable patch eliminates this risk because the microneedles are designed to dissolve in the skin.

What can we use from this in teaching undergraduate A&P?

• Consider mentioning this advance when discussing the layers of the skin, this giving a clinical application to pique student interest.


• When discussing immunity and vaccination, consider mentioning this discovery.


• If you discuss hyaluronic acid when covering histology, this information may help students realize the importance of knowing such details because of clinical applications of materials science.

Want to know more?

• Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch.

• Sachiko Hirobe, et al. Biomaterials. Vol 57 (July 2015), Elsevier. doi: 10.1016/j.biomaterials.2015.04.007
• The original research article.
• my-ap.us/1eXzAud

Microneedle image courtesy of S. Nakagawa

Some content adapted from an Elsevier newsroom release

Protein Mechanism in Neurodegenerative Diseases

Huntingtin

Huntingtin, the abnormal protein that produces clumps characteristic of Huntington disease (HD), can spread from one neuron to another. That's what a recent study has uncovered. Because such protein clumping is observed in other neurodegenerative disorders such as Alzheimer disease (AD) and Parkinson disease (PD), some scientists hope that understanding this newly discovered mechanism of transmission within brain tissue may lead to possible treatments or preventive strategies.

If you want to read more about it, check out the resources I've provided below.

What can we use from this in teaching undergraduate A&P?

• This information can help us answer those pesky "why do we need to know all this if I'm going to be a [insert health profession here]?" challenges when covering the details of protein structure.  The sequence of amino acids and the complex folded structure of proteins really does have real-world clinical implications.  And is already becoming necessary to understand disease mechanisms and treatment strategies.  In real life!
• Discussing the basic idea of this discovery provides a starting platform from which we can jump into discussions of 
• Degeneration of tissues in general and neurodegeneration in particular
• Why neurodegeneration in specific brain locations produces specific neural deficits
• Prions and their possible roles in various disorders
• The possible roles of genetic mechanisms in neurodegenerative disorders
• The need to know details about protein structure (see item above)
• Current directions in medical research—that proteins are hot!

Want to know more?

Neurodegeneration’s Spread

• Ashley P. Taylor. The Scientist. August 4, 2014
• Plain-English article describing the new research showing that pathogenic protein aggregates that accumulate within neurons and are a hallmark of Huntington’s disease can propagate from cell to cell.
• my-ap.us/1kDnJnk

Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons

• E. Pecho-Vrieseling et al., Nature Neuroscience, 13 July 2014, doi:10.1038/nn.3761, 2014.
• The original research article.
• my-ap.us/YKuauI

Huntington disease

• PubMed Health. last reviewed 28 May 2013
• Basic information about HD.
• my-ap.us/1tAVHbM

Why Bother with Protein Folding?

• Kevin Patton. The A&P Professor. 22 May 2012.
• Further discussion of why protein folding is important in the undergrad A&P course; includes links to other resources.
• my-ap.us/1vtd9Ad

Want to Fold Some Proteins?

• Kevin Patton. The A&P Professor. 13 June 2012.
• Introduction of the Foldit game that allows anyone to participate in protein-folding research by playing an online folding game.
• my-ap.us/1l1PYMz

RNA Interference. Again.

Five years ago, I extolled the virtues of teaching a little bit about RNA interference (RNAi) in undergraduate A&P courses.  But for a while it looked like the promise of RNAi in basic and clinical research might be sputtering.  However, a recent article by Eric Bender called The Second Coming of RNAi shows that RNAi "the gene-silencing technique [now] begins to fulfill some of its promises."

I recommend reading the entire article at my-ap.us/1BbxvB9  Before you read it, allow me to reprise my reasons of five years ago supporting my proposal to include RNAi in your course.

What can we use from this in teaching undergraduate A&P?

• RNAi plays a role in defending our cells against viruses by stopping viral genetic code from being translated in host cells


• RNAi likely plays a role in regulating gene activity in a cell by preventing translation of the gene product(s)


• RNAi is increasingly used as method for "knocking out" a particular gene's effects in research animals in order to study the gene's functions


• RNAi is being used to treat genetic disease. . . an application that will likely expand greatly over the next few decades

I'll add two more items to my previous list:

• RNA interference is a mechanism of human disease, as has been demonstrated in some cases of inherited progressive hearing loss (for example).


• Learning about RNAi helps clarify a general understanding of the many roles played by RNA in our lives—some perhaps still undiscovered.

I'm not sure that it's useful to expect beginning undergraduate students to learn the nitty-gritty details of RNAi mechanisms.  But I do think it's valuable to be exposed to the general concept of RNA interference and gene silencing.  A&P students are going to run up against these eventually as they learn about and then administer RNAi-based therapies, after all.  And perhaps we should prepare them.

Want to know more?

The Second Coming of RNAi

• Eric Bender. The Scientist. September 1, 2014
• Article mentioned above. In plain English, it shows that clinical progress in RNAi therapy against liver diseases, the gene-silencing technique begins to fulfill some of its promises. Includes useful illustrations and links to other resources.
• my-ap.us/1BbxvB9

Why do we need to know about RNA interference?

• Kevin Patton. The A&P Professor. 14 April 2009
• My first article promoting the idea of teaching RNAi in the A&P course.  It links to an expanded article with additional teaching resources.
• my-ap.us/1xbq4v6

RNA interference revisited

• Kevin Patton. The A&P Professor. 9 June 2009
• Brief follow-up article that references the role of RNA interference as a mechanism of human disease.  Links to other resources.
• my-ap.us/1oDflzw

RNA Interference Animation and Slideshow

• Nature Reviews Genetics. Accessed 3 September 2014
• FREE animation, slideshow, and poster on RNAi, as well as a link to more details.
• my-ap.us/1roNGYm

RNA Interference BioInteractive

• Howard Hughes Medical Institute. Accessed 3 September 2014
• FREE slideshow with worksheet that students fill out as they view the slideshow.  Links to FREE DVD from HMMI called The Double Life of RNA.
• my-ap.us/1pJ9r5V

Nobel Prize 2014: Super-resolved fluorescence microscopy

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2014 to

Eric Betzig

Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA,

Stefan W. Hell

Max Planck Institute for Biophysical Chemistry, Göttingen, and German Cancer Research Center, Heidelberg, Germany

and

William E. Moerner

Stanford University, Stanford, CA, USA

“for the development of
super-resolved fluorescence microscopy”

Surpassing the limitations of the light microscope

For a long time optical microscopy was held back by a presumed limitation: that it would never obtain a better resolution than half the wavelength of light. Helped by fluorescent molecules the Nobel Laureates in Chemistry 2014 ingeniously circumvented this limitation. Their ground-breaking work has brought optical microscopy into the nanodimension.

In what has become known as nanoscopy, scientists visualize the pathways of individual molecules inside living cells. They can see how molecules create synapses between nerve cells in the brain; they can track proteins involved in Parkinson’s, Alzheimer’s and Huntington’s diseases as they aggregate; they follow individual proteins in fertilized eggs as these divide into embryos.

It was all but obvious that scientists should ever be able to study living cells in the tiniest molecular detail. In 1873, the microscopist Ernst Abbe stipulated a physical limit for the maximum resolution of traditional optical microscopy: it could never become better than 0.2 micrometres. Eric Betzig, Stefan W. Hell and William E. Moerner are awarded the Nobel Prize in Chemistry 2014 for having bypassed this limit. Due to their achievements the optical microscope can now peer into the nanoworld.

Two separate principles are rewarded. 

One enables the method stimulated emission depletion (STED) microscopy, developed by Stefan Hell in 2000. Two laser beams are utilized; one stimulates fluorescent molecules to glow, another cancels out all fluorescence except for that in a nanometre-sized volume. Scanning over the sample, nanometre for nanometre, yields an image with a resolution better than Abbe’s stipulated limit.

Eric Betzig and William Moerner, working separately, laid the foundation for the second method, single-molecule microscopy. The method relies upon the possibility to turn the fluorescence of individual molecules on and off. Scientists image the same area multiple times, letting just a few interspersed molecules glow each time. Superimposing these images yields a dense super-image resolved at the nanolevel. In 2006 Eric Betzig utilized this method for the first time.

Today, nanoscopy is used world-wide and new knowledge of greatest benefit to mankind is produced on a daily basis.

This video is a brief animation of how STED works and how it improves resolution of individual particles.

This video is a longer, more detailed presentation by one of the Nobel laureates (Hell).

What can we use from this in teaching undergraduate A&P?

• Discuss how this technology has enabled us to better visualize the chemicals and structures within our cells, enabling scientists to better understand the structure and function of cell, organelles, microbiome constituents, and other structures of the human body.


• If you do a brief run-through of the theory of microscopy—perhaps in your A&P lab—you can add a mention of this technology.  


• Your textbook or other learning resource may already have an example of this type of microscopy.


• A discussion of this  Nobel Prize could evolve into a meaningful example of how science works, including how incremental improvements in classical tools for observation expand the number of questions that can be answered.


• Use the links below (and images above) to use for a handout and/or teaching slides.

Want to know more?

Resources from Nobelprize.org

• Popular Information 
• Handout: Overview information in plain English
• my-ap.us/1rh0fAJ
• Scientific Background
• Handout: More detailed information includes references to original research articles
• my-ap.us/ZdLJ69
• Advanced Information
• Handout
• my-ap.us/1rh0dsp
• Images
• Can be used in your course
• Abbe's diffraction limit
• my-ap.us/ZR0LA8
• The principle of STED microscopy
• my-ap.us/1ncRH2C
• The principle of single-molecule microscopy
• my-ap.us/1pQbAZ4
• Biographies
• Eric Betzig, 
• U.S. citizen. Born 1960 in Ann Arbor, MI, USA. Ph.D. 1988 from Cornell University, Ithaca, NY, USA. Group Leader at Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
• http://janelia.org/lab/betzig-lab
• Stefan W. Hell, German citizen. 
• Born 1962 in Arad, Romania. Ph.D. 1990 from the University of Heidelberg, Germany. Director at the Max Planck Institute for Biophysical Chemistry, Göttingen, and Division head at the German Cancer Research Center, Heidelberg, Germany.
• http://www3.mpibpc.mpg.de/groups/hell
• William E. Moerner, U.S. citizen. 
• Born 1953 in Pleasanton, CA, USA. Ph.D. 1982 from Cornell University, Ithaca, NY, USA. Harry S. Mosher Professor in Chemistry and Professor, by courtesy, of Applied Physics at Stanford University, Stanford, CA, USA.
• http://web.stanford.edu/group/moerner

Diagrram cretit: Ganbaatar

Micrograph credit: Tesselkaffee

Text adapted from press release from Nobel Media

Sweeteners Alter Gut Microbiome to Promote Glucose Intolerance

I'll never forget when Ira Fritz, my doctoral committee chair, practically slapped a packet of artificial sweetener out of my hand as I was about to put it into my iced tea.  "That stuff will kill you!" he said as he extracted from me an oath to swear off the stuff.  I'm not sure I quite believed him, but to this day I still drink my iced tea unsweetened.

As usual, Ira was right.  Recently another brick has been added to the foundation of his concern about sugar substitutes. Researchers have found that sweeteners such as saccharine, sucralose, aspartame can alter the microbial ecosystem of our gut in a way that promotes the development of glucose intolerance.  Glucose intolerance is part of metabolic syndrome, one of the most significant epidemics of our (or any) era.

At least as interesting as this microbial mediation between our diet and our metabolic function is the fact that only those human subjects who were responders exhibited the changes observed.  This underscores our emerging view about the individualized nature of human nutrition and metabolism.

What can we use from this in teaching undergraduate A&P?

• We have yet another example to share regarding why and how the human microbial system plays such a vital role in our body.


• This may be an interesting story to bring up when discussing immunity in our A&P course, perhaps giving a preview of later topics on the gut microbiome and nutrition/metabolism.


• Nutrition and metabolism are not the same for everyone.  So the basic principles learned in an A&P course are likely to be generally true for humans, but not necessarily entirely true for every individual.


• Yet another example of the principle "you are what you eat."


• And here's another case of continued scientific research refining the story of what we know about human structure and function.  Consider mentioning it when you are explaining scientific methodology and it's relevance to A&P at the start of your course.  An interesting discussion may ensue after asking, "does this mean we should stop using sugar substitutes?"

Want to know more?

Artificial Sweeteners Linked to Glucose Intolerance

• Beth Skwarecki. Medscape Medical News. September 17, 2014
• Article summarizing the recent research.
• my-ap.us/1pkI645

Sugar Substitutes, Gut Bacteria, and Glucose Intolerance

• Anna Azvolinsky. TheScientist. September 17, 2014
• Another plain-English article covering how the consumption of artificial sweeteners results in glucose intolerance is mediated by changes in the gut microbiota in both mice and humans.
• my-ap.us/1qOBVvw

Artificial sweeteners induce glucose intolerance by altering the gut microbiota

• Jotham Suez, et al. Nature. doi:10.1038/nature13793 September 17, 2014
• Research article outlining the discovery of the sweetener-gut-glucose intolerance  link. Includes numerous illustrations.
• my-ap.us/1uLs0Hc

Metabolic Syndrome 

• S Wang, et al. Medscape. Updated 23 April 2014
• Detailed Medscap entry summarizing various aspects of metabolic syndrome.
• my-ap.us/1uLrNUE

Diet Sodas, as Well as Regular Ones, Raise Diabetes Risk

• Miriam E. Tucker. Medscape Medical News. February 14, 2013
• Article summarizing research showing that women who drink large amounts of diet soda are at increased risk of developing type 2 diabetes mellitus.
• my-ap.us/1uLrY20

Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale–European Prospective Investigation into Cancer and Nutrition cohort

• Guy Fagherazzi, et al. American Journal of Clinical Nutrition. January 30, 2013. 
• Original research article about the diet soda-diabetes link.
• my-ap.us/1BQOTLP

Photo: S. Snodgrass

Number of Human Genes Revised Downward. Again.

Genomic researchers in Spain have recently proposed a new, lower number of protein-coding genes in the human genome.  Previously, the number of coding genes was estimated by some at nearly 22,000 in the human genome.  The new estimate is approximately 19,000 protein-coding genes.

How can we use this new information in teaching undergraduate A&P?  Well, first we can update the numbers we use when discussing the role of genes in protein synthesis.  If it fits with our course objectives, we can use this as a way to transition to a discussion of coding vs. noncoding genes.

We also have an opportunity to discuss how science works—we are constantly checking our facts and revising our conclusions to improve the accuracy of our knowledge.  And that the story of genomics is far from complete.

I often tell students that I'm trying to tell them "the last, best story" of the human body's structure and function.  So if my story changes over time, that's a good thing!

FREE image you can use in your course

Want to know more?

Size of the human genome reduced to 19,000 genes

• Science Daily. July 3, 2014
• Press release in plain English based on information provided by researchers.
• my-ap.us/1qrtHWf

Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes. 

• I. Ezkurdia, et al. Human Molecular Genetics, 2014; DOI: 10.1093/hmg/ddu309
• Research article proposing the newly revised number.  Open access to full text of article.
• my-ap.us/1oL7aTh

Want a FREE digital image of the nuclear genome that you can use in your presentation, handout, or other course material?  The image above is in the public domain and can be used in your course materials.

Death spreads throughout body

C. elegans

In class discussions, we talk about what happens when the body dies.  And it's always a bit tricky when the discussion gets around to the idea that not every cell dies simultaneously.

And of course, that can lead to a discussion of how tissue death occurs, even in the case of necrosis that occurs as a result of ischemia or other damage. There are certainly many mechanisms involved—quite a few of which have yet to be clarified.

Recently, researchers have brought a step closer by mapping out some of these mechanisms.  In their report (cited below), they reveal that in the gut of the C. elegans worm, calcium ions flowing into cells cause the lysosomes to burst suddenly.  And we know what that means! Intracellular destruction leading to cell death.

What causes the calcium ions to rush into the cells? Gap-junction ion-channel proteins called innexins (analogous to connexins in humans) open up and allow calcium ions to flow into one cell then the next, producing a wave of destruction along the gut.

In interesting phenomenon is that esters of anthranilic acid (formed from the amino acid tryptophan) in the lysosomes not only produce acidosis in the cytosol, they also fluoresce brightly with a bluish glow during this process of cell death.

The video below shows an amazing anterior-to-posterior wave of fluorescent blue in C. elegans worms as this "wave of death" travels along the gut wall.

Okay, now here's the kicker.  By knocking out the innexin channels, the researchers were able to stop the wave of death!  Whoa!  A cure for . . . death?!

Not so fast.  This worked in a WORM, which is not as complex as a vertebrate like the human.  And it only worked in INJURED worms, not elderly worms dying of old age.  So it won't stave off death entirely—or unusually prolong life—but it could lead to treatments for preventing or reducing necrosis that occurs as a result of ischemia and other injuries.

This information—and that dramatic video—could be an interesting addition to your class.  It ties in why it's important to understand concepts such as:

• ions
• amino acids
• ion flow into cells
• gap-junction ion channels
• lysosomes
• cell death and organismal death
• necrosis (and factors leading to necrosis)
• use of animals in research
• the intersection of basic science research and medical applications

Want to know more?

Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. 

• Coburn C, et al.  PLoS Biology 11(7): e1001613. 2013. doi:10.1371/journal.pbio.1001613
• The original research article.  Includes FREE images and PowerPoint slides you can use in your course.
• my-ap.us/19SRjOG

Glowing, Glowing, Gone: Cell Fluorescence Casts Light on How Death Spreads Throughout Body

• By Christopher Crockett. Scientific American online 2 August 2013
• Brief, less technical, article explaining that researchers have identified a key molecular pathway for animal death that may provide clues for better managing traumatic injury and disease in humans.
• my-ap.us/13MxJjs

New life science journal eLife publishes first articles

Most journals that publish the "big news" in life science breakthroughs, such as Nature and Science, carry with them big price tags for accessing the information they contain.  Unless your institution subscribes, that leaves most A&P professors out of the loop on the information we need to update our courses.  More importantly, it leaves us out of the loop of information that helps us keep the excitement of science alive in our courses.

The Public Library of Science (PLoS) began publishing FREE online science journals a few years ago, and now a new MAJOR free online journal dedicated specifically to the life sciences and biomedicine has emerged.  See my-ap.us/SqSOJM for more information

First announced in summer 2011, eLife is a researcher-led initiative for the best in science and science communication. Backed by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust, the initiative’s first aim is to launch an open-access journal for outstanding advances in life science and biomedicine, which is also a platform for experimentation and showcasing innovation in research communication.

The eLife journal Web site is set for launch by the end of 2012, but the first collection of articles was released October 15 – listed at the eLife Web site with the full content available at the online archive of the U.S. National Library of Medicine, PubMed Central (PMC), and its mirror sites including UKPMC.

According to Randy Schekman, the journal’s Editor-in-chief, “We see no reason to delay the availability of these discoveries. Our editors have identified them as important, inspiring contributions of the high caliber expected for eLife. So, while the launch of our own journal Web site isn’t expected until December, we will best serve our authors, and science, by just getting them out there.”

eLife’s initial collection of content includes these topics that may be of interest to A&P professors:

• A hormone involved in response to starvation that dramatically increases the lifespan of mice in which it is overexpressed, although further research into side effects is needed (Zhang et al.).  Information about this discovery will increase student interest in endocrine function, eh?


• A critical signaling molecule involved in the interaction between a species of single-celled organisms and bacteria – an important advance in efforts to understand the evolution of multicellularity (Alegado et al.).  I often discuss the implications of the serial endosymbiosis theory in my teaching of cell biology— I think this new information may play into that whole scenario.


• How cells cope with the stress of poorly folded proteins, and specifically how fission yeast deploys the same cellular machinery as other organisms but in an unusual and very different way (Kimmig et al.). I've mentioned the importance of understanding protein folding in A&P many times.

Links to the freely available full text for each article, plain-language summaries (the eLife digest), expert commentaries (Insights), and an editorial describing the motivations behind this move, are available at my-ap.us/U7OP25.  I think the eLife digest and the Insights are particularly useful for A&P professors and A&P students to use in expanding their understanding of human structure and function.

Want to know more?

For more information about eLife, visit my-ap.us/S5K9d3.

To sign up for free updates in the areas that interest you at my-ap.us/WToDyp

Content adapted from eLife press release 

That junk is valuable!

During spring cleaning in my household, I'm often heard lamenting that yet another of my treasures has been deemed "junk" and hurled into the "it's outta here" box.  As we've been discovering in science, so-called "junk DNA" is also truly a treasure.

As scientists have been outlining for years, even before the start of the ENCODE project to explore the genome "within and between the genes," the noncoding regions of DNA contain important information that allows cells to regulate the activity of genes.

The ENCODE (Encyclopedia of DNA Elements) just announced the publication of 30 linked papers in Nature and other journals that give us the clearest picture yet of the critical roles played by noncoding DNA. 

The journal Nature has a great site that links many resources about these new discoveries in one nifty "dashboard."  Besides the 30 linked papers, you can access podcasts, news, comments, quick summaries of the ENCODE project, and more.  It's a great place to get up to speed on what's going on, so that we can be more informed about the current state of knowledge as we weave the genomic story into our A&P courses.

You might even find some resources that you can use directly in your course . . . or as supplemental activities.

Explore Nature's ENCODE site at my-ap.us/NatureENCODE

Want to fold some proteins?

In a previous post, I proposed that A&P students should be aware of the basic elements of protein folding.  To follow up, I'd like to mention a interesting phenomenon related to protein folding and "citizen science" using an online game called Foldit.  


The Foldit game is an online puzzle game in which anybody can try their hand and finding which way a given protein folds most efficiently.  Interestingly, this has proven to yield useful results for biochemists not obtainable by traditional methods.

You may want to mention the Foldit game to students.  I've already posted it at my blog The A&P Student.

Want to know more?

Online Gamers Achieve First Crowd-Sourced Redesign of Protein
Jessica Marshall & Nature magazine
Scientific American Online January 22, 2012
[Brief article about recent redesign of a protein by online gamers using Foldit. Original paper published in Nature Biotechnology]
my-ap.us/wRK2bV

Foldit Online Protein Puzzle
Scientific American Citizen Science accessed 23 January 2012
[Brief description of the online game Foldit and the goals of the project.]
my-ap.us/zIV75F

Foldit - Solve Puzzles for Science
[Direct link to portal for the game Foldit]
my-ap.us/wfRQPF

Why bother with protein folding?

For those of you who use (or refer to) my textbooks, you may notice that I've been gradually adding more and more coverage of protein folding to most of them. My newest text (due out in March) adds a bit more to the story. Why bother?  Isn't that way more than beginning students need to know for an A&P course preparing students for health careers?

I submit that beginning A&P students should know a bit about protein folding.

Knowing the very basic principles of protein folding help students visualize the complex shape of proteins.  That, in turn, helps them understand that "it's all about shape" when trying to understand how proteins like enzymes, receptors, and most other proteins work—proteins that they'll encounter many times throughout their A&P course and beyond. 

Besides that, protein folding has become a key concept in understanding not only how the body functions, but how to intervene therapeutically in important diseases.  If a class of therapy based on protein folding is now being developed, a class of therapy that many of our students will likely encounter in their professions, don't we owe it to them to cover the basic ideas of protein folding? 

This latest idea was brought up at a recent meeting of the American Society of Cell Biology (ASCB).  You may want to read the article below, which briefly summarizes some current work being done in developing drugs that affect protein folding systems.  None of the specific  information in the article would be appropriate for A&P students to learn.  But reading it will give the A&P professor better insights about why the concept of protein folding is important for students to learn.  And it gives you a chance to say, "I was just reading about how scientists are now developing drugs based on protein folding . . . " to get their attention in class!

Want to know more?

Protein Folding and Disease: The Path from Bench to Bedside
V. Glaser
Genetic Engineering & Biotechnology News 15 Jan 2012. Vol. 32, No. 2
[Brief, illustrated article that clearly summarizes some recent work in applying principles of protein folding to drug therapies.]
my-ap.us/wFh6F2

Protein folding animation
[Interesting Quicktime animation that shows a protein folding]
my-ap.us/xzWnW4

GCSF Protein Folding Illustration Movie
[Another animation, a bit more complex than the previous one.  Clearly shows different types of models used in most A&P textbooks.]
my-ap.us/xpSisS


The Three-Dimensional Structure of Proteins
[Narrated animation showing four levels of protein structure, including visualization of protein folding.]
my-ap.us/yAS2fr

Artificial life?

Once they "get" the basic idea of molecular genetics, my A&P students become fascinated with those teeny-weeny molecules can have such huge impacts on the structure and function of the body.  On the drive home from campus today, I heard a great story on NPR about the announcement by Craig Venter that his team has successfully created a living, reproducing cell using completely synthetic DNA.  

They did this by using yeast cells to assemble smaller, synthesized bits of DNA and transferring it to living cells, which then reproduced the genome in offspring cells. 

While this is a long way from the claims (and concerns) of "creating artificial life," it is a huge discovery.

If you want to hear more about this, listen to the story yourself at Scientists Reach Milestone On Way to Artificial Life.

.

Crazy artificial genetish

This is just crazy.  I'm still not decided whether it's mad-scientist, what-could-they-possibly-be-thinking? crazy or it's brilliant, why-didn't-they-think-of-this-sooner, life-is-now-complete crazy.

According to a recent post at TheScientist.com, scientists have recently created an artificial system in which a bizarre, created ribosome reads codons in mRNA that are four bases long. You read the correctly . . . instead of reading bases three at a time (like in real life), these little monsters can read a whole different form of genetic language—or genetish, as author Matt Ridley calls it.

This breakthrough allows scientists to build a whole new system of creating proteins—one in which there could be up to 256 different possible amino acids available.  This means that instead of being limited to using only the 22 naturally-occurring amino acids currently available for playing around to produce crazy new proteins, scientists can now also use synthetically modified amino acids with a variety of chemical properties. Modified or synthetic amino acids have no 3-base codons to represent them in natural genetish.

Just a few months ago, we were lauding the Nobel laureates who helped us figure out the structure of the ribosome.  Now we're seeing the creation of artificial ribosomes that translate artificial genetish. I guess this is a huge breakthrough for chemists hoping to synthesize new types of proteins.  It may also provide opportunities for synthetic biologists (scientists attempting to create artificial cells, tissues, and organisms).  It certainly is a great starting point for a sci-fi novel!

Want to know more?

Genetic coding revamp
Jef Akst
TheScientist.com 14 Feb 2010
[Summary of development of a new genetic language.]

Some background from the primary literature:

A chemical toolkit for proteins — an expanded genetic code
Jianming Xie et al.
Nature Reviews Molecular Cell Biology 7, 775-782 (October 2006) doi:10.1038/nrm2005

An evolved ribosome for genetic code expansion
Caroline Köhrer et al.
Nature Biotechnology 25, 745 - 746 (2007) doi:10.1038/nbt0707-745

A network of orthogonal ribosome·mRNA pairs
Oliver Rackham et al.
Nature Chemical Biology 1, 159 - 166 (2005) doi:10.1038/nchembio719

Prions are our friends

OK, let's see if I can remember what I just read about prion proteins (PrPs) . . . I think I read that they can help us store memories.  Oh yeah, that's right . . . and it turns out that they are needed to maintain the insulating myelin sheath around neurons that enables proper conduction of action potentials.

In my Anatomy & Physiology textbook I define a prion as

a term that is short for “proteinaceous infectious particles,” which are proteins that convert normal proteins of the nervous system into abnormal proteins, causing loss of nervous system function; the abnormal form of the protein also may be inherited; a newly discovered type of pathogen, not much is known about how the prion works; see bovine spongiform encephalopathy, variant Creutzfeldt-Jakob Disease (vCJD)

Well, it turns out that prions are not all bad, after all.  In a recent article in Nature Neuroscience, scientists report that certain prions are needed for the axonal signaling to Schwann cells that is needed to maintain the myelin sheath (pictured) and thus maintain normal conduction of nerve impulses.

In another finding reported in the journal Cell, scientists working with prions in sensory neurons of the sea slug found that the clumping of prions that we previously associated only with prion diseases plays a role in preserving memory.  Typically, when prions clump, they for tangles called amyloid plaques in a cell. Apparently, the clumping of certain prions at synapses increase the length of time that a memory is stored at that synapse.

Researchers also found that the neurotransmitter serotonin promotes the formation of the memory-preserving clumps.

More work needs to be done, of course, but these findings may lead to the discovery of a central role for prions in retaining long-term memories.

Want to know more?

Axonal prion protein is required for peripheral myelin maintenance. 
Bremer, J., et al.
Nature Neuroscience. 24 January 2010. doi:10.1038/nn.2483
[Original research article]

Prion protein is not all bad
Tina Hesman Saey
Science News February 13th, 2010; Vol.177 #4 (p. 17) 
[Summary article describing the role of prions in maintaining the myelin sheath, as well as some general insights on the emerging new view of prions.]

Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation
Kausik Si, et al.
Cell Volume 140, Issue 3, 421-435, 5 February 2010
[Original research article included a nifty graphical summary of the central findings.]
Click here for an audio interview with the scientist about this breakthrough

Protein clumps like a prion, but proves crucial for long-term memory
Tina Hesman Saey
Science News web edition : Thursday, February 4th, 2010
[Summary article explaining new research findings and their importance.]

Ribosome scientists win 2009 Nobel Prize in Chemistry

EXTRA! EXTRA! This news just in from the Royal Swedish Academy of Sciences . . .

The 2009 Nobel Prize in Chemistry has been awarded jointly to

Venkatraman Ramakrishnan
MRC Laboratory of Molecular Biology, Cambridge,
United Kingdom

Thomas A. Steitz
Yale University, New Haven, CT, USA

Ada E. Yonath
Weizmann Institute of Science, Rehovot, Israel

"for studies of the structure and function of the ribosome"

As I've mentioned in yesterday's "extra edition" of The A&P Professor, as well as in previous posts, I love to tie major awards and other news about major discoveries in the recent history of science into what we are actually learning in A&P class. And the real people behind these discoveries.

Wow, this morning's announcement for the chemistry prize couldn't have been better timed. Not long ago we wrestled with the story of protein synthesis and my students slowly realized the critical role of the ribosome's structure in that story.

An understanding of the ribosome's innermost workings is important for a scientific understanding of life. This knowledge can be put to a practical and immediate use; many of today's antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive. This is why ribosomes are such an important target for new antibiotics.

This year's Nobel Laureates in Chemistry have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering.

This gives us an opportunity to show how understanding the "basic science" that are teaching translates (ahem) into applications in "the real world."

Want to know more?

"Public" summary
[PDF article intended for the general reader; does a good job of recapping the role of the ribosome within the big picture of biology, includes some nice graphics that you can use in your class plus links for further reading]

Scientific Background
[PDF article directed at those of use with some science background; well-written summary of the ribosome and the evolution of scientific discovery leading to the awarding of this prize; includes some good graphics; comprehensive list of scientific references]

Other resources

Nobel's "useful links and further reading"

FREE image of ribosome's role in translation

FREE image of detailed ribosome structure

Additional FREE ribosome images

NOTE: I apologize to my email subscribers who received two posts yesterday instead of one. I've adjusted the timing so you should only get one delivery on these rare occasions when I have an "immediate" post to send to you.

{Some content of this post came from the Nobel organization}

Can a borrow a cup of copernicium?

Last month, I gave you the heads-up on the newly confirmed element 112. Now, we have a proposed name for it . . . Copernicium (Cp).

An eponym for the 16th-century Polish scholar Nicolaus Copernicus (pictured)—the guy widely known for his ground-breaking heliocentric view of cosmology—the new name is not yet official. Copernicium is the name proposed by the discoverers . . . and that usually becomes the official name unless somebody finds out it means something nasty in some human language somewhere.

This eponym thing is interesting. In human anatomy, we are shunning eponyms—in chemistry, it seems to be embraced. Hmmm. And get this . . . Nick Copernicus's name is in fact adopted from the name of element 29, copper (Cu). The name is the Latinized form of Mikołaj Kopernik—his surname having been based on his family's business (copper work).

So tuck that away in your trivia file, eh?

Click here for more information.

Element 112

Just in case you mention the total number of "known" elements when reviewing basic chemistry at the beginning of your A&P course . . . you should be aware that we're now up to 112.

Ununbium (Uub), as well as several proposed elements beyond 112, are listed in the periodic chart in Figure 2-1 (p. 34) in Anatomy & Physiology. As I stated, this is NOT essential information for A&P students, but a little bit of background to keep you up to date on the state of science. And you NEVER KNOW when it might come up, eh?

Researchers in Germany, then later in Japan, were able to manufacture atoms of Uub. The first succesful team (in Darmstadt, Germany) will be suggesting a permanent name to the International Union of Pure and Applied Chemistry (IUPAC) to replace the placeholder name "Ununbium." The IUPAC should be announcing the new name within a few months.

Here's a video from the Periodic Table of Videos (background)
http://www.youtube.com/watch?v=dqMksokDbeA


Here's another video updating the Periodic Table of Videos
http://www.youtube.com/watch?v=KJ_TZUWdlYU


{Image of electron shell diagram for Ununbium, the 112th element in the periodic table of elements from Pumbaa (original work by Greg Robson)}

Human fertility gene found

Here's another little nugget to throw into your lecture on reproduction . . . researchers recently identified a gene that improves fertility in humans.

The CFTR (cystic fibrosis transmembrane conductance regulator) gene in chromosome 7 (q31.2) may have a single amino acid substitution (valine instead of methionine in exon 10) that is correlated with improved fertility among male parents.

You may recall that different mutations of the CFTR gene may instead cause cystic fibrosis (CF) [see Anatomy & Physiology 7ed. p. 119-120, 1118-1119].

This nugget can be used in your A&P class to emphasize the concept that the amino acids assembled during translation from the genetic code have to be in the specific and exact order in order to function properly. Mutations to this gene, for example, can reduce normal function (as in a CF mutation) . . . or they can improve function (as in the fertility-enhancing mutation described here).

This nugget can also be used to explain why it's important to know about amino acids and protein structure . . . and the relationship of the genetic code to this structure. Perhaps it's a good idea to even be able to recognize the names of amino acids like valine and methionine--news such as this will become more and more commonplace as the years go by and this will become common and expected knowledge among health professionals.

Obviously, this new information can color any discussions you have in your course regarding genetic mechanisms in general and genetic mechanisms of disease in particular.

Want to know more? Check this out:

Human Fertility Gene Found
Elie Dolgin
The Scientist 3 April 2009
[Good summary article about the discovery, which was presented on April 2, 2009, and will be published in the Proceedings of the National Academy of Sciences.]

[Click the image above for a FREE illustration that you can use in your class.]

Net calories

We're teaching about metabolism and nutrition . . . then comes the perennial question for which we have no good answer:

"Well then, which diet is best?" Meaning, which of the popular weight-reduction diets du jour are most scientifically sound, based on what we've just learned?

This is a great question!

Not because I have a great answer--I don't.

It's a great questions because I don't have an easy answer. We (meaning "the science community") simply don't know enough yet to say for sure. So it's a great question to talk about that aspect of how science works.

It's also a great starting point to ask, "based on what we are learning now, which do you think would be best?" This opens up possibilities to apply concepts, such as

• how nutrients are converted to different forms (lipids, carbs, proteins),
  
• how nutrients are stored in the body,
  
• how metabolism works,
  
• what an energy budget is,
  
• how metabolic imbalances can created pH imbalances and other problems,
• the role of vitamins and minerals in the body,
  
• the role of fiber in the digestive tract,
  
• what metabolic rates are,
• the role of hormones,
• and . . . well . . . this list goes on and on . . .

One concept that I often emphasize in this context is the balance between how many calories come in to the body (food calories) and how many calories go out of the body (metabolic calories expended). Much of the difference is stored* . . . and the favorite way we store it is as body fat. This concept is emphasized in my textbooks as well.

But what about all these different approaches to weight-loss dieting. Or just having a healthy diet in general? What about:

• low-fat vs. high-fat diets
• good-fat vs. bad-fat diets
• low-carb vs. high-carb diets
• processed foods vs. unprocessed foods
• high-sodium vs. low-sodium diets
• high-fiber vs. low-fiber diets
• and this list also goes on and on . . .

You've probably heard about the latest news on this topic . . . something that can inform your next discussion of this topic . . . and perhaps spark additional discussions, eh?

A study recently published in the New England Journal of Medicine suggests that the best weight-reduction diet is as simple as reducing calories in a diet that can include just about anything, as long as it's proportionally high in "heart-healthy" foods such as vegetables and fish.

So the "it's all about the calories" notion is pretty close to the mark, eh?

Want to know more? Check out these resources:

Weight-Loss Winner: A Diet High in Fiber, Low in Calories
by Coco Ballantyne
Scientific American online. 25 February 2009
[FREE article summarizes the recent study]

Stick to a Low-Calorie Diet and It Will Work
by Nathan Seppa
Science News online. 25 February 2009
[Another FREE summary of the recent study]

Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates.
Sacks, F.M., et al. 2009.
New England Journal of Medicine 360(Feb. 26):859-873.
[FREE full-text article about the latest research.]

The Science of Weight Loss
Scientific American online. Accessed 27 February 2009
[FREE set of online resources related to this topic.]

Calorie Calculator
freedieting.com Accessed 27 February 2009
[FREE online calculator estimates the daily calorie needs of an individual based on age, gender, size, exercise habits, etc. Has advanced options and links to additional calculators. Interesting class, lab, online, small-group, or homework activity.]

* some of the calories are lost in the feces

[photo by NatalieTraynor at Flickr.com]