Posts Tagged ‘RNA’

The Common Cold

January 27, 2009

A few weeks ago had a small cold.  I wondered what was really going on inside my body.  It turns out this is a complicated and fantastic story about the immune system.  First let’s over the high-level events of the common cold:

  1. A Rhinovirus infects the upper respiratory system
  2. Leukocytes detect the virus
  3. Leukocytes initiate inflammation
  4. Adaptive immune system is activated
  5. The virus is eliminated

Now let’s check these steps out in more detail:

Infection

A virus (usually a rhinovirus) enters your nose and lands on your adenoids (part of your tonsils) the virus binds to the epithelial cells with proteins called cell adhesion molecules.   You can think of it like cellular Velcro, but instead of little plastic hooks they’re made of protein structures which interlock.  This binding changes the structure of the virus’s protein shell (the capsid), which in turn causes myristic acid to be released onto the infected cell.  This acid creates a pore through which the virus can inject its RNA.  Once RNA is within the host cell, it begins replication through RNA transcription.

Detection

The immune system has cells which contain special “pattern recognition receptors” (PRRa) made of protein, which bind with various pathogens including viruses.   Examples of these cells are leukocytes (white blood cells) including macrophages and dendritic cells which both bind with viruses.  If a leukocyte binds with a rhinovirus (or other pathogen) with its PRRs, then it will internalize it in a process called phagocytosis.

Here is an incredible video of another leukocyte called neutrophils chasing down a bacterium and phagoticizing it.  Neutrophils is about 14 microns across, and I believe this video was shot over several hours:

Inflammation

These activated leukocytes respond to the binding of pathogens by release chemicals called cytokines.  These chemicals are one way which cells communicate and organize their efforts.  In the immune system, releasing cytokines, as well as other chemicals, draw more leukocytes to the site of the infection through an amazing process of cellular motion called chemotaxis.   Chemotaxis is basically proteins moving in response to their chemical environment, which causes a cell to propel itself  in a specific direction to reach its chemical goal.  This process escalates the inflammation in a feedback loop of chemotaxis, phagocytosis, and cytokine release.  These released chemicals also cause the familiar symptoms of inflammation: redness, heat, swelling, pain, and loss of function.

In my next post I’ll talking about the adaptive immune system which is pretty incredible.

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Our Ribosome

November 23, 2008

When you think about nano-machines, which perform a complex mechanical operations at the molecular level, you might think of science-fiction and the promise of nanotechnology.  Well, one of the most incredible nanomachines is in our cells: the Ribosome!  The magnificent contraption created after hundreds of millions of years of evolution reads an mRNA strand as input, and outputs a protein made of amino acids.  (Yes, we read about these chilralitic wonders in a previous post.)

The ribosome is found in all living cells, both Eukaryotes (protozoa, algae, humans, etc . . .) and Prokaryotes (bacteria and archaea).  It is composed of 2 subunits, one large and one small.  For Prokaryotes the small subunit is labeled 30S, and the large subunit 50S.  For Eukaryotes, they are 40S and 60S respctively.  (The S is for Svedberg units, a measure of sedimentation.)  The are a composed of a complicated intertwining of proteins and rRNA and look like this:

the small subunit on the left contains an RNA molecule (cyan) and 20 proteins (dark blue); the large subunit on the right contains two RNA molecules (grey and slate) and more than 30 proteins (magenta). The image also shows a transfer RNA (orange) bound to the active site of the ribosome. (Harry Noller, UCSC)

The small subunit on the left contains an RNA molecule (cyan) and 20 proteins (dark blue); the large subunit on the right contains two RNA molecules (grey and slate) and more than 30 proteins (magenta). The image also shows a transfer RNA (orange) bound to the active site of the ribosome. (Harry Noller, UCSC)

Here’s how the process works in Prokaryotes:

  1. After mRNA is transctibed from DNA, it reaches (I’m not sure how), the small Ribosome 30S subunit.  Attached to 30S are 2 initiation factors, IF1 and IF3, which keep 30S seperated from the larger 50S.  the mRNA contains a special start codon (usually AUG), which marks the beginning of the mRNA sequence to read for protien synthesis.  A codon is a set of 3 genetic bases, which corresponds to a specific amino acid, but more about that later.
  2. IF2 binds to the intitiator tRNA which holds the start anticodon, and IF2 brings this initiator tRNA to the ribosome’s P-site.  If the initiator codon is AUG, the anticodon on the initiator tRNA will be UAC.  Those sequences will bind together.
  3. Once IF2 engages, it deposits the initialtor tRNA at the P-site, then all IFs disengage.  This allows 50S to attach with 30S, surround the P-site.
  4. The tRNA which contains the anticodon for the next codon triplet in the mRNA sequence is guided into the A-Site inside the ribosome.  Each tRNA contains an anticodon on one end and an amino acid on the other end.  It is these amino acids which will be bound through peptide bond formation to form our protein!
  5. After the bond is formed, the tRNA in the P-site is ejected out of the ribosome, and the tRNA in the A-Site is ratcheted into its place.  Then the cycle repeats until the special stop codon on the mRNA is reached.
  6. When the stop codon is reached, the subunits disengage, and IF1 and 2 re-engage 30S, starting the process all over gain.

There is a large amount of research into modeling this incredible process.  One example is this remarkable video produced by the Weizmann and Max-Planck Institutes:

UPDATE:  There is some debate as to the realism of this video.  Unfortunately I have not found much information on it, which leads me to believe that this video is only remotely representative of actual processes.   It is still quite instructive, so please just take it with a grain of salt.