Monday, October 13, 2014

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  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.

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.

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.

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.

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.

Wednesday, October 8, 2014

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


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

  • Popular Information 
  • Scientific Background
    • Handout: More detailed information includes references to original research articles
  • Advanced Information
  • Images
  • 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.
    • 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.
    • 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.

Diagrram cretit: Ganbaatar
Micrograph credit: Tesselkaffee
Text adapted from press release from Nobel Media

Monday, October 6, 2014

Nobel Prize 2014: The Brain's Positioning System

The Nobel Assembly at Karolinska Institutet has today decided to award

The 2014 Nobel Prize in Physiology or Medicine

with one half to

John O´Keefe

and the other half jointly to

May-Britt Moser and Edvard I. Moser

for their discoveries of cells that constitute a positioning 
system in the brain.

How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? This year´s Nobel Laureates have discovered a positioning system, an “inner GPS” in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function.

In 1971, John O´Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus that was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. O´Keefe concluded that these “place cells” formed a map of the room.

More than three decades later, in 2005, May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells”, that generate a coordinate system and allow for precise positioning and pathfinding.

Their subsequent research showed how place and grid cells make it possible to determine position and to navigate.

The discoveries of John O´Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?

How do we experience our environment?

The sense of place and the ability to navigate are fundamental to our existence. The sense of place gives a perception of position in the environment. During navigation, it is interlinked with a sense of distance that is based on motion and knowledge of previous positions.

Questions about place and navigation have engaged philosophers and scientists for a long time. More than 200 years ago, the German philosopher Immanuel Kant argued that some mental abilities exist as a priori knowledge, independent of experience. He considered the concept of space as an inbuilt principle of the mind, one through which the world is and must be perceived. With the advent of behavioural psychology in the mid-20th century, these questions could be addressed experimentally. When Edward Tolman examined rats moving through labyrinths, he found that they could learn how to navigate, and proposed that a “cognitive map” formed in the brain allowed them to find their way. But questions still lingered - how would such a map be represented in the brain?

John O´Keefe and the place in space

John O´Keefe was fascinated by the problem of how the brain controls behaviour and decided, in the late 1960s, to attack this question with neurophysiological methods. When recording signals from individual nerve cells in a part of the brain called the hippocampus, in rats moving freely in a room, O’Keefe discovered that certain nerve cells were activated when the animal assumed a particular place in the environment (Figure 1). He could demonstrate that these “place cells” were not merely registering visual input, but were building up an inner map of the environment. O’Keefe concluded that the hippocampus generates numerous maps, represented by the collective activity of place cells that are activated in different environments. Therefore, the memory of an environment can be stored as a specific combination of place cell activities in the hippocampus.

May-Britt and Edvard Moser find the coordinates

May-Britt and Edvard Moser were mapping the connections to the hippocampus in rats moving in a room when they discovered an astonishing pattern of activity in a nearby part of the brain called the entorhinal cortex. Here, certain cells were activated when the rat passed multiple locations arranged in a hexagonal grid (Figure 2). Each of these cells was activated in a unique spatial pattern and collectively these “grid cells” constitute a coordinate system that allows for spatial navigation. Together with other cells of the entorhinal cortex that recognize the direction of the head and the border of the room, they form circuits with the place cells in the hippocampus. This circuitry constitutes a comprehensive positioning system, an inner GPS, in the brain (Figure 3).

A place for maps in the human brain

Recent investigations with brain imaging techniques, as well as studies of patients undergoing neurosurgery, have provided evidence that place and grid cells exist also in humans. In patients with Alzheimer´s disease, the hippocampus and entorhinal cortex are frequently affected at an early stage, and these individuals often lose their way and cannot recognize the environment. Knowledge about the brain´s positioning system may, therefore, help us understand the mechanism underpinning the devastating spatial memory loss that affects people with this disease.

The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialized cells work together to execute higher cognitive functions. It has opened new avenues for understanding other cognitive processes, such as memory, thinking and planning.

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

  • The role of the hippocampus and it's place cells could be briefly discussed as you explore the cognitive functions of the brain.

  • A discussion of this year's Nobel Prize could evolve into a meaningful example of how science works, including the use of discoveries in animals that can later be applied to learning more about human structure and function.

  • Information revealed by this discovery could be discussed when discussing human disorders, such as Alzheimer disease, that involve impairments of spatial orientation and/or place memory.

Want to know more?

Here's a video in which May-Britt Moser and Edvard I. Moser explain their research, which you can use in your course discussion.

2014 Nobel Prize announcement

  • Official announcement, which includes photos of the laureates and links to related information.

Scientific Background: The Brain’s Navigational Place and Grid Cell System

  • accessed 6 October 2014
  • Plain English hand-out that can be used with your students.  Illustrated with clear diagrams.

Nobel Prize in Medicine Is Awarded for Discovery of Brain’s ‘Inner GPS’

  • L. Altman The New York Times. OCT. 6, 2014
  • Plain English article summarizing the discoveries.

The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely‐moving rat.

  • O'Keefe, J., and Dostrovsky, J. (1971). Brain Research 34, 171-175.
  • Original research paper describing key discoveries for which this prize is given.

Place units in the hippocampus of the freely moving rat.

  • O´Keefe, J. (1976). Experimental Neurology 51, 78-109.
  • Original research paper describing key discoveries for which this prize is given.

Spatial representation in the entorhinal cortex.

  • Fyhn, M., Molden, S., Witter, M.P., Moser, E.I., Moser, M.B. (2004)  Science 305, 1258-1264.
  • Original research paper describing key discoveries for which this prize is given.

Microstructure of spatial map in the entorhinal cortex.

  • Hafting, T., Fyhn, M., Molden, S., Moser, M.B., and Moser, E.I. (2005). Nature 436, 801-806.
  • Original research paper describing key discoveries for which this prize is given.

Article adapted from Nobel Media press release