which came first riboswitches or ribozymes?

We have discussed RNA a lot in the lecture class.  There is much more to talk about regarding these versatile molecules.  For instance, some RNA molecules can act like enzymes.  Origin of life enthusiasts believe that this supports the notion that early life was RNA based....the RNA world hypothesis. 

But on the other hand, some RNA is regulated by many outside factors.  Some of these factors interact with a region on the mRNA called riboswitches, these are binding sites within mRNA for molecules which help control the production of the protein which results from that particular RNA.  These molecules are the "dependent" cousins of the more independent ribozymes.  It would be interesting to see if ribozymes are controlled by riboswitches or they are dependent on them.

1 Provide an example for how riboswitches work.  What is the advantage of having a switch within the mRNA which is used for the translation process? (i.e., why could not the switch be outside the sequence?).

2 Riboswiches show that mRNA sequences are used for more than just making a protein...the same sequence can bind to factors which control the sequence.  What is the significance of one molecule of RNA having multiple functions?

3 Can you envision a scenario for how roboswitches could have evolved?

Telomeres and Spock



"my what lovely telomeres you have" said the wolf-virus
to the little red-riding hood-cell

 


  Cells have their own version of Spock's famous missive "Live long and prosper."  Cells make this statement using repetitive DNA sequences found on end of chromosomes called "telomeres." Telomeres act as a cap on the end of chromosomes.  They are thought to be another "guardian of the genome" of sorts.  Some scientists believe that longevity is related to telomere length. In fact, telomeres have been shown to be longer in individuals who are healthy and exercising compared to individuals who are under stress.



What's even more interesting is that telomeres are thrown out or lost during cell division so they have to be "remade" using a specific polymerase.



How do telomeres protect DNA?

What is the significance of telomeres being made from repetitive DNA? (what is repetitive DNA and what is it good for?).

What determines how long telomeres are?

How are telomeres related to cell function?

Some bacteria have telomeres,  so from one perspective it looks like they were handed down via evolution.  Why use what appear to be accidental sequences to make the ends of chromosomes? Is there some advantage or design feature inherent in these chromosomal pieces?

inTRON Legacy... the problem of snRNPs (the smurfs of cell biology)

A recent study highlights the importance of spliceosome components by showing that a rare genetic disease is caused by a mutation in a

snRNP.  The spliceosome is a machine made of several snRNPs.  These molecular scissors cut precisely the right location on the DNA to remove an intron and promote the ligation of exons.  Prokaryotes appear to do just fine without introns. 

 So what is the purpose of introns?  What overall function do they provide for eukaryotes?  Why use such a complex splicing operation for a function which appears to do nothing more than rejoin exon regions?   How do evolutionary biologists propose that snRNPs and spliceosomes evolved? Is this good design or is this entire process wasteful and therefore not good evidence for design in nature?

location location location, position of chromosomes, gene expression, and bad design?

garage DNA ..what a mess?

The amazing organization of the eukaryotic nucleus was shown in a fascinating article in Scientific American.  It turns out that chromosomes occupy certain locations in the nucleus.  Some chromosomes reside at the periphery of the nucleus and others near the middle.  Some chromosomes also appear to favor being next to "buddy" chromosomes.  It is not yet totally understood why chromosome position is important, except that it is very crucial to cell function.  One nucleoskeletal protein lamin, helps tether the chromosomes in place.  Mutations in lamin are responsible for all sorts of disease conditions, including progeria, or premature aging.


Also it appears that the chromosomes near the nuclear periphery are more quiescent than chromosomes near the center.  The chromosomes in the center are more involved in gene expression.  No one knows how the chromosomes get directed toward a specific place in the nucleus.  I find it quite amazing that this overall structure can be maintained because there is so much DNA in the nucleus.  Remember in its stretched out form DNA is  hundreds of thousands of times longer than the nucleus diameter.   I have trouble just keeping a few power cords untangled in the garage.  Just imagine my garage packed full of tightly wound-up and partially wound-up power cords  and that I need to find one cord in particular to unwind and use and I must do this while literally swimming through a tangled maize of power cords.  I think you would suffer from "power cord" entrapment before you could even reach the power cord you need. 


1 Investigate progeria and hypothesize how nuclear organization could lead to this syndrome and other disease states.  Many diseases are related to chromosome structure and function including cancer, does this support the notion of bad design?....i.e., does the fact that some aspects of cell structure are more involved in promoting disease states show that a designer of the cell or life is unlikely ?




2 Describe how nuclear organization and chromosome location could evolve during the evolution of the nucleus from a prokaryote ancestor? What are some of hurdles that evolution would have to overcome?

the creation of life, the end of vitalism and Dr Venter’s Frankenstein cell

Last year, biologist Craig Venter created the first artificial cell.  Or did he?  Apparently he was able to manufacture a genome and stick it in a bacterial cell which had its DNA neutralized or removed.  Many news outlets claimed that he created the first synthetic life form. 

The creation of a living cell from scratch would be no small feat considering the billions of atoms and thousands of proteins, and hundreds of lipids and carbohydrates that would have to be put in the correct place.  If we used a cooking analogy, it would be like constructing a single cookie one speck of flour and one speck of sugar at a time….that would be some cookie and it would take a long time to get every single speck of flour, sugar, baking soda, salt all in the right place.

However, that is not what Venter did.  So did he really create the first synthetic life form?

One of the nations leading bioethicists, Arthur Kaplan has inferred that this is the end of the idea that life has a spiritual dimension or a “vitalism"; an idea that has persisted in philosophical biology for hundreds if not thousands of years.

1 How did Venter make his genome and insert it into the bacterium?    How did he remove the original DNA?

2 Did he create a living cell?  Share your view.

3 Is this the end of vitalism?

"stretchy pants" and hemidesmosomes

In the movie Nacho Libre',  Nacho is a wrestler (luchador) and likes to wear the "stretchy" pants the luchadors wear.  Living things made out of cells can be very firm like plant structures, but in animals,  cells are very stretchy and can participate in making structures like human skin and other tissues which are very malleable.  In our next topic in class we will discuss how eukaryotic tissue cells communicate with the outside world. Certain outside stimuli involving the extracellular matrix can promote shape change in cells and it can cause them to stretch and contort in ways that seem extreme.  Some cells must be stretched and shaped in order to form the shape of internal organs and for wound healing.  How do you stretch a cell and not break it?  Answer:  very carefully.


In a recent paper in Nature, a mechanism for stretching cells is proposed.  The mechanism centers around fascinating membrane protein complexes called hemidesmosomes.  Hemidesmosomes have been known for quite some time to be attachment structures which attach cells to other cells or the extracellular matrix.  Hemidesmosomes also attach to cytoskeleton components inside cells.  But new studies suggest that hemidesmosomes are also mechanosensors able to detect outside forces which squeeze and stretch cells. Hemidesmosomes communicate with intracellular cell signaling components such as kinases and other proteins.  Here again we have another case where a protein is involved in multiple functions.  The end result of the squeezing and stretching is elongated cells that contribute to the final shape of an internal organ for example during embryogenesis.


1 Review hemidesmosome structure and suggest a mechanism for how they could be involved in cell stretching? 


2 What would be the overal mechanism that would drive the cells to take on shapes which would contribute to the final morphology of an internal organ?


3 How do cells know how much force they can take before they rip apart?

Life on Mixotricha paradoxa

No, this is not a newly discovered planet but a flagellated Trichomonad found in the gut of the termite (Mastotermes darwiniensis). Paradoxa helps digest wood fiber in the gut of the termite. It appears that paradoxa moves by using its flagellum. But a closer inspection shows that the flagellum is perhaps only a steering device and the entire structure moves by the locomotion of hundreds of bacteria on the surface of paradoxa.
 
Thus we can document yet another function for the flagellum.  There are several kinds of bacteria on the surface of paradoxa and some are held in what appears to be specialized brackets on the surface of paradoxa.  Some of these bacteria contain their own flagellum and some of the bacteria are spirochetes.  The spirochetes are thought to provide the locomotion on the surface of paradoxa.  It would seem that a most efficient way for this organism to move would be to communicate with its surface motors when it wants to stop or start or go faster.

And there is good reason to want to move fast because Mixotricha paradoxa is hunted and eaten by other creatures lurking in the shadows.  Maybe this is a good reason to live in a  nice safe place like a termite gut.

Questions:

1 Spirochetes move by rotating.  How can a rotating twisting bacterium promote locomotion of paradoxa and yet stay attached to its host if its entire cell body rotates?

2 If paradoxa communicates with its motor bacteria, what form of communication would this be?

Cellular UPS and bad design

As I have mentioned in class, I think that bacteria and viruses appear to possess  features consistent with the idea that they are designed to deliver agents to cells.  For instance, their size is conducive to cell interaction and many possess elaborate motors , docking and delivery systems.  In fact, the bacterial flagellum which is often advertised as having one function, actually demonstrates many functions, i.e. it is a docking/binding agent as well as a motor, it also appears to be a receptor in some instances.  Thus the flagellum demonstrates co-option; it has more than one function,  an idea that many intelligent design theorists don’t like.  In addition some bacteria can control the actin polymerization inside cells inducing the cells to make “cellular arms” or pseudopods.  Thus they  induce the cell pseudopods to engulf them and they enter the cell in this manner.  Recently, researchers have used  bacteria to deliver a virus to a cell which induced profound genetic changes in the cell.  Viruses themselves possess several elaborate mechanisms for engaging cells and entering cells.  Viruses not only deliver genetic information to cells, but they can deliver proteins, they can control intracellular biochemistry and they can deliver membranes and membrane proteins.  Take for instance the flu virus.  It is an enveloped virus.  Technically when it leaves a cell it takes along some membrane from that cell.  Could it be that everytime you get a flu, you also get some proteins and membrane components from your friends?   What are the long term and short term implications of this?  But then again, viruses and bacteria can cause lots of problems.  If these creatures were designed as extracellular delivery organelles, is this the best design?.... because it appears that with a few "slight modifications" they can become agents of cellular destruction.

Questions:

1 Discuss the microbial extracellular organelle theory as described above.  What are its strengths and weaknesses as a theory?

2 If bacteria and viruses are designed delivery agents, why does our immune system try to eliminate them?  Or does it?

the dreaded dihydrogen oxide cell toxin: beware!!

Dihydrogen oxide is one of the most lethal cellular toxins.  It kills cells by causing them to swell uncontrollably and then burst, or in some cases to shrivel up like a crumpled piece of paper.  However most all cells on earth have been able to resist this toxin by using a membrane protein to prevent its deadly actions.  But even more interesting dihydrogen oxide or water is required for life and the aquaporin channel helps maintain a non-lethal concentration of this precious but deadly fluid.

Aquaporin is a fascinating integral membrane protein.  It is able to "filter" water into the cell by keeping other polar or charged molecules around the same size as water  out of the pore.  Plant, animal and bacterial cells have aquaporin channels. 

Questions:

1 How does aquaporin operate as a selectivity filter?  What would happen to cellular metabolism if it did not operate as a selectivity filter?

2 The complexity and requirement of aquaporin for cellular life appears to be a problem for the evolution of the first cells.  Or is it?  Some plants cells can take in water without aquaporin.  Could this represent a more ancient water controlling mechanism?  Check it out and comment on what you have learned.

cell suicide and the schizophrenic Jason Bourne organelle

We are discussing the lipids and proteins which make up the membranes in cells in lecture.  One of the most bizarre membrane proteins is called the mitochondrial permeability transition pore (mPTP).  This is a cluster of proteins which connect the inner mitochondrial membrane with the outer mitochondrial membrane and forms a pore.  The pore only  forms briefly under extreme cell stress conditions and essentially really messes up the mitochondria so that it reverses its function, and begins consuming ATP which  usually kills the cell.   In many cases this activity leads to apoptosis also called programmed cell death. This drastic measure often occurs after local cellular stress or stress of internal organs like during a heart attack.    Just like Jason Bourne in the Bourne Identity, the identity of the mitochondria is difficult to determine, it is a unique mystery organelle in many ways, and like Bourne, it  commits violence when stressed out....or is it that it commits violence to protect itself? Just what could the mitochondria be protecting? 

Questions:

1 What are the different ways that a cell can die?

2 What is apoptosis?  What are its benefits?

3 What would be the advantage to having the vital energy producing organelle also double as a death organelle?

4 Considering the idea that the mitochondria is a specialized internal bacterium, are there parallels in function between  mitochondria and extracellular free living bacteria with respect to energy production and promotion of cell death?