Observing with Street Lights

Observing with Street Lights
Dark sky sites not always necessary to see the Milky Way (This image was taken ouside of a B&B in Julian, CA)

Wednesday, March 25, 2020

Excellent free video lecture series on virology while stuck in our burrows; Looking into how viruses use symmetry and potential energy to their advantage;

Greetings from Palmia Observatory

Well here we are again holed up in our burrow, with only a few trips out to pick up food or occasionally just to look at the sky and see if the clouds have gone away.  It is hard to concentrate on much anything else but learning to adapt to the virus.  So, this post will cover some interesting aspects of viruses, picked up during my homework reading in virology, and how they rely on physics principles of symmetry, free energy and stability.

First up, though we should mention an interesting article forwarded to the OCA mail server, in which the author lays out a whole bunch of epidemiological models covering different mitigation strategies for dealing with the virus.  I can't say anything about the validity of the author's claims, but you can see right away how complicated the issues are with figuring out what drives the decisions to set policies for public policy.  The "hammer" in the title refers to strict isolation measures to block the transmission of the virus quickly, so that we can get back to making a living, and the "dance" refers to the ongoing monitoring and control as needed to bring the hammer back as needed.  The paper has main charts and graphs based on epidemiological modeling and seems to be very detailed.  I hope some kind of strategy like that might get us out of this situation until a vaccine is available.  Anyway, if you follow this type of stuff, check it out at:
https://medium.com/@tomaspueyo/coronavirus-the-hammer-and-the-dance-be9337092b56


In the previous blog post, I mentioned a book on the "Molecular and Cellular Biology of Viruses."  It is a good reference book for interested reader, but if you like to listen to lectures, rather than reading a textbook, there is a series of free YouTube lectures titled " Virology" with Professor Vincent Racaniello, Columbia U.

I am finding this series of lectures very interesting.  You should have had at least some introduction to molecular biology but the professor does a good job of introducing each topic.  This is a convenient way to keep busy and learn something about the virus, which we now shelter in place to keep away from.  You can check out the lectures at:
https://www.youtube.com/playlist?list=PLGhmZX2NKiNldpyRUBBEzNoWL0Cso1jip&app=desktop

Screenshot of Virology Lectures 2020  on YouTube (Source: Vincent Racaniello, Columbia, U.)
Screenshot of Virology Lectures 2020  on YouTube (Source: Vincent Racaniello, Columbia, U.)

In order to talk about symmetry and viruses we must first remember some of the basic biology of virus, which is in this lectures series, and I will review briefly.  My review is that of a student, so keep that in mind as you read this summary.

Now that the complete human genome has been sequenced  we find a mystery in that only about 1.5% of the genome is associated with making the proteins from which are made.  What are all of the other base pairs doing?  Some of them are leftover additions made by viruses.  The same is found when other organism's genome is sequenced.  We see that all of life is based on the same general base pair basis and that every animal, plant, bacteria and virus are all interrelated and we share a common history.
A big part of the human genome comes from viruses (Source: Vincent Racaniello, Columbia, U.)
A big part of the human genome comes from viruses (Source: Vincent Racaniello, Columbia, U.)

This genome sequencing also applies to viruses and phylogenetic trees can be prepared for viruses too.  This way the slight genetic differences between viruses, caused by mutations, allows one to track the history of viruses and find their closest relative.  Professor Racaniello told how the current version of the coronavirus now circulating around the world has a closest relative in a virus common to bats.
Phylogenetic analysis shows closest relative between mutating viruses (Source: Vincent Racaniello, Columbia, U.)
Phylogenetic analysis shows closest relative between mutating viruses (Source: Vincent Racaniello, Columbia, U.)

We need some more biological background before we can talk about the symmetry principles found in viruses.  As astronomers we naturally think in terms of distance in light years or megaparsecs and wavelengths of light measured in nanometers (nm).  Viruses are in the 20-1000 nm range.
Viruses are very small; mostly smaller than the wavelength of light (Source: Vincent Racaniello, Columbia, U.)
Viruses are very small; mostly smaller than the wavelength of light (Source: Vincent Racaniello, Columbia, U.)

How do you see viruses?  They are a bit smaller for optical microscopes, even though some of the effects of viruses on cells can be seen.  I remember when using x-ray crystallography to find the structure of biomolecules was the primary method, but now electron microscopy and especially Cryo-electron microscopy can achieve much the same resolution and do it much faster.
The tools of viral structural biology (Source: Vincent Racaniello, Columbia, U.)
The tools of viral structural biology (Source: Vincent Racaniello, Columbia, U.)



Compare these two images of a poliovirus.  The one on the left was done with x-rays and the image on the right was done with CryoEM.  Now, the resolution of CryoEM approaches the same 3 nm range.
Different images of Poliovirus for different instrumental resolution (Source: Vincent Racaniello, Columbia, U.)
Different images of Poliovirus for different instrumental resolution (Source: Vincent Racaniello, Columbia, U.)


The principles of CryoEM start with an electron microscope but instead of staining the samples, the samples are fast frozen instead.  The frozen samples have enough contrast that the structure can be seen without staining.  The techniques was recognized with the Nobel Prize in Chemistry in 2017.

CryoEM freezes rather than staining the sample (Source: Vincent Racaniello, Columbia, U.)
CryoEM freezes rather than staining the sample (Source: Vincent Racaniello, Columbia, U.)

We need to review the common connections between viruses and living cells. Each cell has to carry out hundreds of complex chemical reactions and a central part of these reactions is that they occur inside of a membrane that separates the cell from the outside environment.  Some material can diffuse through the cell membrane, but other molecules must be able to pass through the membrane in a controlled manner.  In this next slide we see that the cell membrane is covered with many different types of proteins that are able to control the inflow and outflow of other molecules.  These molecules are necessary to maintain the life of the cell.  When various nutrients and other molecules outside of the cell bump into the cell membrane randomly, they also interact with the proteins that poke through the cell membrane and then are brought into the cell if needed.  In the blog post from last week, we mentioned that the receptor used by the coronavirus is the ACE2 receptor
All cells have embedded proteins to facilitate transport across the membrane (Source: Vincent Racaniello, Columbia, U.)
All cells have embedded proteins to facilitate transport across the membrane (Source: Vincent Racaniello, Columbia, U.)

The ACE2 receptor is located in the cell membrane and regulates the amount of ACE (never mind what this stands for now).  For anyone on high blood pressure medication you know that removal of high levels of ACE from the blood is a key therapy.  But the use of these medications apparently works by increasing the number of ACE2 receptors in the cells in the lungs and blood vessels and might be be reason why more elderly patients are more susceptible to the coronavirus.  Again, this is my student view and interpretation of the situation and might not be valid.

Just in case you are curious about what the ACE2 looks like, check out the ribbon diagram for ACE2 as shown in Wikipedia.  Each ribbon section corresponds to the long chain of amino acids that make up the protein or enzyme.  The ACE2 receptor weighs in at somewhere around 90k Daltons, which o my student approximations represents about 800 amino acids.  Without going into an biochemical detail, the ribbon diagram shows the 3-dimensional structure and location of the proteins that make up the protein.
ACE2 receptor ribbon diagram (Source: Wikipedia)
ACE2 receptor ribbon diagram (Source: Wikipedia)




Viruses also carry signaling molecules that poke outside their capsid structures.  These spikes and knobs, and the corona like spikes on the coronavirus, also interact with the cell and are able to be brought into the cell.  The cellular chemistry is such that if an outside molecule has the right signaling molecule as part of its structure, is brought into the cell.  Again we see that viruses incorporate and use the same signaling molecules that are necessary for each cell that is required to carry out its metabolic processes.
Viruses have surface mounted proteins to unlock membrane receptors  (Source: Vincent Racaniello, Columbia, U.)
Viruses have surface mounted proteins to unlock membrane receptors  (Source: Vincent Racaniello, Columbia, U.)


The next slide summarizes the overall process.  The graphic shows the virus particle entering the cell at which time it sheds its protective capsid coating and then the internal cellular machinery transports the DNA to the cell's nucleus, where the normal cellular machinery dutifully turns out the components needed to make more virus particles.  Once the virus DNA and capsid coat are complete, normal cellular machinery transports the particle to the cell wall and it is released to carry on its infection outside the cell.
Viruses cross the cell membrane and release genetic DNA/RNA  (Source: Vincent Racaniello, Columbia, U.)
Viruses cross the cell membrane and release genetic DNA/RNA  (Source: Vincent Racaniello, Columbia, U.)
Ok, now finally, we get to return to the main topic of the physics of the symmetry of the virus.  The following slide describes how the capsid coat is fabricated and assembled.  The virus DNA is the template to make all of the components needed to assemble more virus particles.  Of particular interest are the molecular subunits make go into making the capsid protective coat.  Note how in this example, three identical molecules just fit together to make a triangular structure.  The triangular structure then assembled together so that 20 triangles make up on 20 sided icosohedral structure, which is the capsid coat.
Viruses have highly symmetric structures to protect its DNA  (Source: Vincent Racaniello, Columbia, U.)
Now each of of those 60 subunits are quite complex proteins with their own special structure so that fit closely together.  Three subunits form a lightly bonded structure, held together by ionic bonds, not covalent bonds, that resembles a triangle.  Then these 20 triangles for the 20 sides of the icosahedron.

In this next screenshot, which uses the ribbon notation you can see that the structure of of a typical subunit, which represents a 3-dimensional model of the actual protein.  The ribbon notation (here where each color, red, blue, brown, and yellow, represents and actually captures the 3-dimensional structure of the protein being modeled.

Viruses have highly symmetric structures to protect its DNA  (Source: Vincent Racaniello, Columbia, U.)
Ok, we finally have reached the point where symmetry comes into the world of viruses.  In the next screenshot we see the basic structural unit of a virus.  The capsid protects the viral DNA and has the symmetry of an icosahedron, which is a 20 sided structure, made up of 20 triangles that fit together to enclose a space.  Many virus capsids are composed of 20 sides, each made up of three polypeptide molecules.  It is much easier to forgo with the ribbon diagrams and just show the icosahedral structure as shown in the screenshot below.
The capsid is icosahedran of 20 sides, each made from 3 identical components  (Source: Vincent Racaniello, Columbia, U.)
The capsid is icosahedron of 20 sides, each made from 3 identical components  (Source: Vincent Racaniello, Columbia, U.)

We are now at a point to recognize why this capsid structure is so important.  First of all it protects the viral DNA when the virus particle leaves the cell.  Secondly, the capsid structure is easily assembled inside the infected cell, because the structure self-assembles from subunits manufactured in the cell, and with the viral DNA inside, the virus particle can then exit the cell and begin anew the infection process.

The virus particles are said to be metastable.  They are just stable enough so that they can survive transport outside of the cell and yet when they get inside the cell they can transition to a lower energy state by ejecting their capsid protective coat.  The graphic below shows how this energy transition is much like a load spring in that no outside energy is needed as long as the virus can surmount the energy barrier at which time it is all downhill then in terms of energy.  It is interesting to note that these chemical reactions use ionic bonding, rather than the more energy intensive covalent bonding which typically requires energy carriers like ATP to complete the process.  So, in one sense, the virus is able to complete its journey without relying on any additional energy from the cell, once that is all of the viral components have been manufactured by the cell and its energy sources.
The potential energy of virus construction is like a load spring  (Source: Vincent Racaniello, Columbia, U.)
The potential energy of virus construction is like a load spring  (Source: Vincent Racaniello, Columbia, U.)



Viruses are able to achieve this metastability and low energy requirements by using symmetrical arrangement of components.

Metastability is achieved by symmetrical use of ionic bonding of subunits  (Source: Vincent Racaniello, Columbia, U.)
Metastability is achieved by symmetrical use of ionic bonding of subunits  (Source: Vincent Racaniello, Columbia, U.)


Viruses are not constrained to have capsids made out of just 60 identical proteins.  In order to contain larger and more complex types of DNA, the capsid coat and box must be made larger.  The symmetry of larger viruses is based on the same symmetry of the icosahedrel structure but more subunits are combined.  So instead of 60 identical subunits, the example virus shown below uses 720 copies of the subunit.

Larger viruses can be based on using more identical symmetrical subunits  (Source: Vincent Racaniello, Columbia, U.)
Larger viruses can be based on using more identical symmetrical subunits  (Source: Vincent Racaniello, Columbia, U.)






Magnetic marbles show closed structures made from  groups of 5 or of  6 (Source: Vincent Racaniello, Columbia, U.)
Magnetic marbles show closed structures made from  groups of 5 or of  6 (Source: Vincent Racaniello, Columbia, U.)

Ok, so that is enough viral homework for this time.  The lecture series is much more informative and thorough than I have been in this short summary, so check out the actual lectures if you are inclined.  I hope you do see though the connection to symmetry and low energy requirements.

Now, I have to transition to being one of the many judges for the OC Science Fair, which this year has been forced to be conducted over the internet.  It won't be the same atmosphere like in previous years where you have hundreds of students and their projects all collocated at the fair grounds.  I'm not sure how it will all work out, but at least the students won't have the whole event cancelled or postponed.



Until next time, here from our burrow, stay sane, stay safe,

Resident Astronomer George



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