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More on the Lac Operon

A while ago I wrote two posts about the Lac Operon here. The first pointed to an animation by McGraw Hill Publishers that did a pretty good job illustrating how the operon works. In the second post, I highlighted the notion of polycistronic messages (more than one gene per mRNA molecule) and how this allows for control of a number of related genes at once – a trait not shared by eukaryotic cells. In that second post, I also finished with a graph of how cells grow in the presence of glucose and lactose.

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Cell Growth in the presence of glucose + lactose – As glucose is depleted, cells adjust to lactose digestion

One feature of that graph (reproduced here) that is notable is a little bump in the growth rate as glucose runs out and the cell converts to lactose digestion. A second important feature is that the rate of growth slows when the cell is burning lactose as its primary fuel.

 

Together, these features suggest that the cell is regulating lactose digestion very closely. In fact, there are two primary mechanisms of this regulation to appreciate. The first is that the lactose-digesting enzymes are controlled together on an operon that is regulated by lactose itself (or at least we can assume so for simplicity’s sake). In the absence of lactose, no lactase enzymes are made and no lactose is used as fuel. The reason for this is obvious when you look at the slope of cell growth under glucose metabolism (left) and lactose metabolism (right). Clearly, growth is SLOWER when lactose is used as fuel.

Therefore, so long as there is glucose, it is pointless to digest lactose at the same time. So it is best to only turn on the lac operon in the ABSENCE of glucose – regardless of whether lactose is present of not.

If glucose is absent and lactose is absent, turning on lactase enzymes is still useless. However, slow growth is better than no growth. So we should have a mechanism to turn on the operon when there is lactose in the environment.

Here’s a matrix of ideal regulation:

Screen Shot 2014-03-31 at 2.18.05 PM

How can a little, mindless bacteria achieve this exquisite control?

Simple: By using two regulators. One for glucose and one for lactose. Only when both conditions (glucose-, lactose+) are met do we make lactase.

Structure of the Lac Operon

operon1

First, lactose itself serves as an inducer. In the absence of lactose, a regulator protein binds to a DNA site between the polymerase binding site (the promoter) and the structural genes (the enzymes). When the regulator binds, its presence physically prevents the progress of RNA Polymerase.

When lactose is present, it binds the repressor protein in a way that causes its shape to change in a way that can no longer bind the DNA. The repressor then drifts away from its binding site allowing RNA Polymerase a clear shot to the structural genes.

operon2

However, RNA Polymerase is not always parked on the promoter waiting for the repressor to be removed. Its binding requires another protein to help stabilize its interaction with the DNA. This second protein is the CAP protein. The Catabolite Activated Protein. However, CAP alone will not bind either. It requires a signaling molecule called cyclic AMP (cAMP). cAMP is readily broken down when glucose is in the cell, so it only accumulates when glucose is absent. In that case, cAMP accumulates and binds to the CAP protein, which then binds to the CAP site. This site is located adjacent to the promoter, but on the side away from the structural genes. When CAP binds, it assists in recruiting the RNA polymerase to the promoter.

operon3

Therefore, if only one condition is met, it is insufficient to promote gene transcription. Only when the CAP+ cAMP protein is bound will the Polymerase be recruited. And only when lactose is present, will the repressor protein let the Polymerase pass.

operon4

In terms of the matrix we set forth above, we can see that these molecular interactions result in exactly the regulation that is optimal:

post-operon

 

 
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Posted by on March 31, 2014 in Uncategorized

 

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Something for my Micro Students to do Over Spring Break

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Posted by on March 18, 2014 in Uncategorized

 

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Micro Crossword

 

 

 

 

 

 

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Posted by on March 12, 2014 in Uncategorized

 

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“This blog is our last hope ”

“No, there is another.”

Exam I for Microbiology nears. Where will the extra credit questions come from? Will they all be found here? Perhaps. But there is A New Hope.

 
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Posted by on February 19, 2014 in Uncategorized

 

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Agriculture, emigration, deforestation and Malaria

ImageWhen malaria first began to infect humans is something of a mystery. It was a mystery that I hadn’t thought about much before now because … well, I don’t know, it just never occurred to me.

However, recently a colleague mentioned that there was a connection between it and the beginnings of agriculture. Despite the fact that I should know better, I dismissed the idea out of hand. That’s too recent, I thought. There’s no way that could be the case.

The idea of a connection was originally suggested by Frank Livingstone, who “suggested that Plasmodium falciparum (which is by far the deadliest of the several parasites that cause human malaria) had jumped into Homo sapiens from chimpanzees. He speculated that the rise of agriculture had led to human encroachment on wild forests, giving the chimp version of the bug, P. reichenowi, the chance to find a new host.” 1 

Despite my dismissal, the idea did come back to me late last night and I started to look into what was published on the subject. The first thing I found was one of Scientific American’s 60 second science podcasts on the possible connection between recent deforestation in South America and a resurgence in Malaria.  “Researchers looked at stats for 2006 …[and] compared those cases to deforestation in the same health districts over the previous 10 years. They found that a loss of just four percent of forest cover was associated with nearly 50 percent more malaria cases.”2

As always, correlation isn’t causation, but something is happening, and because Malaria is more common in open areas than forests, causation isn’t much of a stretch. And, if malaria does increase when land is cleared of forest, the connection to the advent of agriculture may not be far fetched at all.

Humans started domesticating animals and farming the land about 10,000 years ago , so we do have a date to shoot for in our estimate. The question is, ‘was malaria widespread prior to ~8000 B.C.E.?”

One way to ask this question was to question whether Malaria was with us before we (humans) left Africa, or more recently. This moves the timeframe back to about 50,000 years ago (a reasonable landmark prior to agriculture). One way to ask this question is to look at diversity of the parasite’s genes. Just as the greatest diversity among humans occurs in Africa with less diverse groups coming out from this population, the same should be true of the microbe.

“The researchers found that genetic diversity did indeed decrease at greater distances from Africa. The correlation is very strong, says lead author Francois Balloux of the MRC Centre for Outbreak Analysis and Modelling in London, and the pattern matches human migration out of Africa, which scientists believe started some 50,000 to 60,000 years ago.”3 ( See here and here

For a visual representation of the genetic argument for the origin of malaria, see the map below:

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                                         Genetic Variation of Malaria                                                     (grey dots represent possible sites of origin)

Whether Livingstone’s idea may be correct or not probably has no bearing on the idea that human disease originated in chimps and does nothing to undermine the possibility of a connection between recent outbreaks of disease and clearing land for farms.

 

References

1. “The source of malaria” The Economist. Aug 4th 2009.

 2. “Plasmodium falciparum Accompanied the Human Expansion out of Africa “Kazuyuki Tanabe  et al. Current Biology, Volume 20, Issue 14, 1283-1289, 17 June 2010

 3. “When Humans Left Africa, Malaria Came Along” MARTIN ENSERINK. Science Now. 18 June 2010.

 

 
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Posted by on January 30, 2014 in Uncategorized

 

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MicroBiology Test Questions

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Mixed Culture

Despite the surfeit of responses to my call for General Biology Test questions earlier this week that I had to wade through (read sarcastically), I thought I would yet again offer the opportunity for anyone (Students!?) to present potential test questions. If there is anyone out there who would like to try their hand at it, please respond here in the comments section with your proposed question(s).

Topics for this exam include:

-Laboratory techniques (primarily microscopy and culturing methods)

-Cell composition/organelles/functions, comparing and contrasting prokaryotes and eukaryotes

-Prokaryotic cell biology

-Eukaryotic cell biology

-Viral biology

-metabolism / flow of energy through living systems

-cell culture / growth patterns / nutrition

 
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Posted by on October 23, 2013 in Uncategorized

 

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Soylent….

ImageSoylent Green is a great movie.

Oh, and it’s people.

See my review of what happens just before the crash of a ‘J’-shaped growth curve here.

 
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Posted by on October 1, 2013 in Uncategorized

 

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Herd Immunity

In MicroBiology class we’re still a long way from our immunology unit, but we have started talking about some basic principles of the immunity and vaccination, including the idea of ‘herd immunity’. This is the notion that even incomplete vaccination may be sufficient to prevent the spread of an infection through an entire population.

In this video, Scientific American’s Dina Fine Maron explains Herd Immunity very simply.

http://link.brightcove.com/services/player/bcpid910142956001?bckey=AQ~~,AAAAAFNl7zk~,OmXvgxJOvrGd04F7pX4DjTcq0KXtMvCb&bctid=2632175457001

Interestingly, as I started writing this, I stumbled upon the old crap movie, Outbreak – I’ll also be calling this film crap on my film blog, 100FilmIn100Days.

 
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Posted by on August 31, 2013 in Uncategorized

 

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First Quizzes tomorrow…

Image I mentioned in my classes that I sometimes post extra credit hints here – but not always. Just enough to make it worth checking once in a while and help buoy my stats.

In class last Thursday someone mentioned that they heard I liked to post extra credit questions about Twin Peaks (a favorite series), but that was last semester. I’m sure I won’t be able to resist throwing a couple in at some point. And, after all it’s always a good idea to see that TV doesn’t always have to be predictable and mundane – sometimes it can be awesome.

If I am giving any hints, it’s that this year, I’ve been watching a lot of movies- especially ones from the 70s and 80s – and writing reviews on my other blog, the now-incorrectly titled, 100FilmsIn100Days. So perhaps, we’ll see a little of that nice Dutch Colonial on Long Island from time to time. 

But not all of my extra credit questions come from incidental materials. Sometimes, they’re  serious, about subjects like the Measles outbreak I discuss below or material that I think is cool, but too detailed or tangential to be tested on for credit.

I look forward to getting back in class. See you soon.

 
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Posted by on August 26, 2013 in Uncategorized

 

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Jeopardy, coffee and cookies

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Gameboard for tomorrow’s In-class Jeopardy

Now I’ve done it.

I often feel like saying things out loud is a curse against me. I’m expecting to get up early and make some fresh coffee and cookies for tomorrow’s Micro Exam #1 Review.  But, with the curse and all, I do worry…

The one thing I do have going in my favor is a longing for chocolate chip cookies. For some reason I have not been baking as much lately, but I’ve been trying to get back in the habit. The last two weekends I have made bagels though, so perhaps it will happen.

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Bagel Recipe adapted from Laurel’s Kitchen Bread Book

So, tomorrow, after two cancelled classes due to inclement weather:

Micro: Open review of all material, discussion of the next chapter in Vaccinated (hmmm, I’ve lost track of where we are…), quiz on the last chapter of this unit(Ecology, growth and nutrients) and then potential exam question jeopardy.

General Bio: Continue / finish  cell division and cancer (both covered in chapter 5 of the text), then discussion of the latest chapter of Your Inner Fish (again, I’m at a loss. The chapter after teeth…).

I’d get up and check these things, but I am trapped under a large, sleeping cat who is known to be ferocious when disturbed, so I’d rather keep my hands.

 
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Posted by on February 27, 2013 in Uncategorized

 

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