The lac Operon

This article has appeared separately at For the Sake of Science.

By Michael Hawkins

The lac operon of E. coli is the classic example for describing inducible prokaryotic gene expression. One excellent video description of it can be found here.

The jist is this. Not all genes are turned on all the time. There are ones which are needed constantly, others which are only needed in specific types of cells, and then others which are ‘turned on’ in specific situations. It is on this last point which I will focus.

In order for a gene to be ‘turned on’, it must be ‘off’ in the first place. All this means is that an organism’s (relevant) DNA is not being transcribed, thus preventing translation and the manifestation of proteins. The way this occurs in E. coli by means of the lac operon is that the lac repressor is bound to a DNA sequence.

A repressor is itself a protein. It binds to an organism’s DNA, thus preventing RNA polymerase from transcribing anything. This is a physical blockade; the repressor prevents the RNA polymerase from physically attaching and running along a specific sequence of DNA. This is the default position for an inducible repressor.

The way the repressor is removed is simple to understand. It has a specific shape to it which enables it to bind to the DNA sequence. However, this shape can be changed if lactose is present. The lactose will bind to the repressor, thus causing an allosteric change in shape. This means the repressor is no longer the specific shape needed to attach to the DNA, so it releases its ‘grip’.

This release allows the RNA polymerase to continue with transcription. This, eventually, turns to translation. In this stage, enzymes are created, two of which are ß-galactoside permease and ß-galactosidase (there is a third which can be ignored here). The former of the two is membrane-bound. This means it becomes embedded in the cell membrane. This quickens the transport of lactose from outside to inside the cell. Think of it like a tunnel through which only specific shapes can fit.

Once these specific shapes (lactose molecules) pass into the cell, ß-galactosidase breaks them into their constituents, one of which is glucose. This is used as a key source of energy in many organisms, including E. coli.

Once concentration falls, lactose molecules are no longer bound to the repressor, making it free to resume its normal duties attached to DNA.

Question 1 and Respect

By Michael Hawkins

It is necessary to briefly address the ugliness of Question 1. The results were abysmal: 52% of Mainers are bigots.

It would be a mistake to forget the analogy consistently drawn by No on 1 supporters. That is, this is like the past denials of civil rights for racial minorities.

Yes on 1 supporters never bothered to show how same-sex marriage infringed upon anyone’s rights. From this reason it must be concluded that “bigot” is the most appropriate term for these people.

Yet there’s an unjustified apprehension surrounding this label. Those who fought for liberty would do well to remember that the aforementioned analogy was more than just words. It meant something.

Do away with the undue respect. A bigot is a bigot is a bigot. Declare it loudly.

RNAi: Watching Your Back

The following has appeared on For the Sake of Science. The article in the physical copy of Without Apology has slightly different wording for the sake of print.

By Michael Hawkins

RNAi is an arrestingly interesting little mechanism for protecting the health of cells. The “i” stands for interference, and with good reason. RNAi is made up of a series of molecules which work to detect and destroy possible viruses and RNA which could be viruses.

It was first detected in 1986 when an attempt was made to make a really, really purple flower. The reason was purely for aesthetics, but it would prove to be far more important.

Knowing the gene which coded for purple pigmentation in petunias, geneticists made the logical conclusion and figured adding a bunch of those genes to the flowers would increase the depth of purple coloring in them. But as it turned out, they were wrong. In fact, they were remarkably wrong. Instead of deep purple flowers, they produced white flowers. Not a hint of purple anywhere.

No one had an answer to why would be. It took 12 years until researchers came up with the answer (and another 8 until they were awarded a Nobel Prize).

When viruses invade a cell, they ‘seek’ to make copies of themselves by utilizing the available DNA source. Post-transcription, this comes out with a funny shape due to the RNA making a mirror image of itself. The RNAi then recognizes this strange shape and destroys it with dicers. But it doesn’t stop there. Any sequence which comes out of the nucleus thereafter is also destroyed. This prevents any of the viruses (hopefully) from being translated and replicating (thus exploding out of the cell and infecting other cells).

Something similar happened when the geneticists tried making the super purple flowers. There wasn’t a mirror-image RNA sequence, but there was a funny sort of shape created by all the extra purple pigmentation genes. The RNAi recognized this as a potential virus and began destroying it. All of it. This meant there were no genes for purple getting translated into proteins.

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

So far this is pretty exciting stuff. It’s a post-transcriptional defense mechanism against viruses no one ever knew existed. But it has so much more potential than just as a passing curiosity.

Think about it. If RNAi can essentially turn off genes by destroying them through a sort of sequence-detection, then what stops it from curing diseases? This discovery has the serious potential to cure all the major ailments facing the world today: AIDS, cancer, Alzheimer’s. There has already been success in treating macular degeneration. This is a disease where too many blood vessels are growing in the eye. It damages the retina over time and makes vision majorly cloudy and blurry. There are simply too many genes for blood vessels being produced. But one way to stop this disease is to stop that blood vessel growth. To achieve this, a patient is given an injection which contains a copy of the gene with its mirror image (two mirror strands of DNA). The RNAi detects this misshape and destroys it. It then destroys all other likewise sequences. The same principle could be applied to any number of diseases.

There is an excellent NOVA video on RNAi which can be viewed here. It’s certainly worth watching (and only 15 minutes long).

November edition of Without Apology

I have just received the newest edition of Without Apology. All the articles are up now and I will be distributing it pretty soon.

One of my personal favorites is by Ryan D’Alessandro, Levels of Faith. It’s nice to have someone else contribute. Speaking of which, anyone with good ideas is welcome to write for my paper. You won’t get paid, but I am willing to mail copies of the physical publication out.