April 29th, 2008 ecoli
What’s one of the first thing students learn in high school about nucleic acid molecules? It’s that DNA is double stranded and RNA is single stranded. Not only is this fundamentally incorrect, such type of “linear” thinking is, I would argue, a ‘dangerous’ line of thinking, that may be hard for students to escape from.
Any biochemistry student can tell you that, not only can certain types of RNA form secondary and tertiary structures, but that these structures are critical to understanding the catalytic activity of RNA. This has important revelations for evolution (the RNA-first world hypothesis) and for molecular biology.
Microbiology Bytes ran a segment on The shape of HIV RNA (see image below). The higher order, 3 dimensional structure of HIV RNA could play some important role in viral replication and pathogeneiss
This example serves to illustrate the important point that higher order RNA structure could more important in biology than we could have imagined. Therefore, if we keep giving students the impression that RNA (and other molecules) are linear and static, than they could carry with them a false veiw of biological models.
Coincidently, this also is another reason that computational and mathematical modeling in biology will become all important in the coming years. As it turns out, biochemical structures are just too complex to realistically model without computers (at least not easily).
And, as it turns out, even knowing three dimensional structures may not be enough. Carlos Simmerling from Stony Brook University does computational modeling of biomolecular systems (specifically proteins and nucleic acids) as dynamic entities. In other words, intra-interactions, as predicted by mechanics, cause molecules to “move and shake.” These molecular “vibrations” caused by electrostatic interactions could also greatly potentially affect reactivity of molecules in ways we could have never predicted without computer modeling. Simmerling also develops tools to view these molecules in their energetic states. Here’s a video from Simmerling’s group of the enzyme HIV Protease.
These developments stress the need for new scientists (yes, even biologists) to think mathematically and artistically. We need to be aware of all three dimensions (plus the time dimension) in order to work towards building accurate models of biological and biochemical systems.
Posted in biochemistry, link out, microbiology, musings | 2 Comments »
April 23rd, 2008 ecoli
Microblogology shares a study by the Evanston Northwestern’s MRSA screening program that demonstrates that the most effective ways to control infectious diseases can also be the cheapest, and least ’scientific.’ To study epidemiology is to be smart about pathogens. Where are they coming from, how do they infect, what physical barriers can we set up to stop the spread of pathogens from patient to patient?
The study found that 8.5% of their patients carried MRSA into the hospital (carried, not necessarily infected with). By isolating these patients and taking special precautions, in terms of hygienic practices, the hospital was able to cut down hospital-acquired infections 70%.
This is a more cheaper way to control MRSA than drug development, and it doesn’t give the bacteria a chance to development new antibiotic resistance in the first place. Simple cleanliness and hygiene can probably to attributed to the lessening of the roles of infectious pathogens to the human death rate perhaps even more than antibiotics or vaccines. We seem to have forgotten this along the way; that chemicals and not efficient planning is the more effective method of preventing infections.
Posted in link out, medicine, microbiology, news | No Comments »
April 13th, 2008 ecoli
Small Things Considered reports on a scientific finding that shows that antibiotic resistance in bacteria strains taken from soil samples is fairly common. Even though in some of these samples, they would be unlikely to have come into contact with man-made antibiotics. Testing 18 antibiotics from man-made and natural sources against 11 different samples, researchers did not find any sample that didn’t have bacteria that could metabolize at least 1 antibiotic.
Its an interesting find, which has implications for medicine and health, but is it surprising? I would tend to disagree. Given the rate that bacteria can evolve antibiotic resistance, it stands to reason that there should bacteria exist in nature that can metabolize them.
I quote Paul Orwin who left a comment in the above blog post:
I thought it was fairly clear that in the environment, there are lots of bacteria making antibiotics, and others that can break them down and/or resist them… I can’t see any way that this doesn’t affect clinical use of antibiotics. First, we know that there is plenty of movement of bacteria between soil and host organisms. Second, we know there is plenty of gene transfer going on in both environments. Therefore, there is a very high probability that within a soil microbial population, there is a potential pathogen (Burk and Pseudo being pretty strong contenders) that eats antibiotics for breakfast.
Posted in evolution, medicine, microbiology | 1 Comment »
April 11th, 2008 ecoli
This could provide a new area of evolutionary microbiology. Apparently, Campylobacter jejuni and Campylobacter coli trade so much genetic material via horizontal transfer, that the two species are merging.
Visit Not Exactly Rocket Science for more information.
Posted in evolution, microbiology | No Comments »
March 26th, 2008 ecoli
So I’m giving a journal club presentation in about an hour (as of 6, when I started this) and I figured I’d write a quick blog post about it.
The urinary tract is a multi-organ system that opens to the external environment and, as a result is prone to infections from various pathogens. Approximately 50% of women will get at least one urinary tract infection (UTI) in their lifetime. Uropathogenic Escherichia coli (UPEC) is responsible for 80% of community acquired UTIs, so it is an important pathogen to study.
There are essentially four stages in the current UTI model. Attachment of UPEC to the walls of the urinary tract, invasion of host epithelial cells, replication within those cells, and exfoliation of the epithelial cells concurrunt with bacterial efflux.
My presentation is primarily concerned with the first stage of this process, namely attachment or adherence. UPEC adhesion to the cell wall is absolutely required for initiation of infection, which makes adhesins molecules attractive candidates to study, for the ultimate purpose of vaccine creation. In addition to initiating infection, adherence prevents mictruition, or the ‘washing out’ of UPEC by urine flow throughout the urinary tract. Another important factor is that these adhesin proteins can act as surface antigens and be recognized by the host immune system.
Evading immune response would then become a primary ‘goal’ of UPEC, from selection pressures from the immune system. There are several homologous types of adhesins, and each has various roles in the infection process. In a multi organ system, a bacteria may want to express different adhesins at different times. This would help the organism adapt to microenvironments and conserve resources by limiting coexpression. In addition this could help UPEC evade host immune response by ‘hiding’ key surface antigens. This is known as phase variation.
I’m primarily concerned with a specific adhesin known as pyelonephritis-associated pili (Pap). These pili bind to uroepithelial cells and are responsible for symptomatic UTIs. The expression is controlled by a single operon (promoter, operator, structural gene sequences). UPEC contain several homologous copies of this operon, which have variation in their function.
So, we know that phase variation can control the expression of analogous adhesins, because the gene expression is regulated by different mechanisms. But, homologous copies of the pap operon are controlled by the same mechanism, even though they can have slightly different functions. How can a bacterium control the expression of these different pap operons?
The answer lies in the their very sequence variation. Sequence variation in the genes that encode their epigenetic regulators is selected for. These variation changes the functioning of the epigenetic proteins so that the expression can be modulated or the gene activators turned off. The expression of some copies of the operon are favored, and this is selected for by the host immune system.
References:
Makrina Totsika, Scott A. Beatson, Nicola Holden, David L. Gally (2008) Regulatory interplay between pap operons in uropathogenic Escherichia coli , Molecular Microbiology 67 (5) , 996–1011
Posted in evolution, microbiology | No Comments »
March 25th, 2008 ecoli
So what’s with academics infatuation with facial hair? I suppose its perhaps less common these days, but facial hair is certainly more commonly seen in universities than on the street. Jake Young’s theory (from Pure Pedantry) is that it extends from the necessary slovenliness that comes with being a grad student.
In any case, having a beard can pose problems, especially for those microbiologists, because beards happen to be an excellent substrate for microbes. It then becomes as issue of balancing wisdom vs. safety.
Posted in microbiology, musings | 2 Comments »
March 21st, 2008 ecoli
My father was diagnosed with early stage Lyme disease this morning, so in honor of him I want to talk a little bit about Borelia burgdorferi.
Lyme disease was described a few decades before the cause was known. The present form became studied after outbreaks occured in the area around Lyme, Connecticut, giving the disease its popular name.
B. burgdorferi is a spirochete bacteria, meaning that it has a helical coiled shape. It was first identified by Jorge Benanch, of the State University of New York at Stony Brook, who developed the first critical ELISA antibody test that could test for the presence of the bacteria. Dr. Benanch just so happens to also be the boss of my department and his wife was one of my high school biology teachers (now there’s something wikipedia can’t tell you). Soon after it was isolated by Willy Burgdorferi, for whom the bug was named.
The life cycle of Borrelia is interesting because they require ticks for transmission and mammals to feed on. Tick larvae become infected with Borrelia during the larvae or nymph stage when they feed on white-footed mice. Borrelia remains in the tick as it advances in its life cycle to adult. The adult ticks then feed on small mammals or humans, transmitting the spirochete where (in humans and dogs) it can become pathogenic. However adult ticks preferentially feed on white-tailed deer (no immediate relation to white-footed mouse) and is the source of the name ‘deer tick.’ The adult tick has to feed on deer blood for at least three days in order to be able to reproduce. Borrelia is nonpathogenic to deer.
This is an interesting commensal/parasitic relationship between these three organisms. The ticks rely on deer and Borrelia relies on the ticks. They are barely aware of the others existence, yet they have evolved together in a unique sort of hierarchy.
Posted in evolution, microbiology | 2 Comments »
March 21st, 2008 ecoli
Taking Swansont’s lead, I’m declaring an annual Talk Like a Biologist Day. As far as I know, there is no such day already, so I’m going to take the initiative in saying that there needs be one. The date is as yet to be determined, but some possibilities are April 22nd (Earth Day) and July 18th (birthday of Robert Hooke, discoverer of the cell). Leave a comment if you like one of these two dates, or you would like to propose a different one. This is a collaborative work in progress, so don’t be shy.
So in order to talk like a biologist, you’ll need to become familiar with the jargon and how to use it in every day situations. Allow me to provide some examples and feel free to add your own.
Is something distracting you from getting your work done on time? Don’t worry, it’s not your fault, it’s just due to an “allosteric interaction.”
Any type of regular route is a “pathway.”
Don’t talk about how someone looks, but you should discuss their “phenotype.”
Tough day at the office? If you snap at your co-workers, blame it on negative “environmental stimuli”
If something is happening here, it’s “autonomic.” Far away is “somatic.”
Murdered your child in a fit of frustration? Don’t worry, just pass it off as “strategic infanticide.”
Don’t pick out your outfit this evening, “apply selection pressures” to your wardrobe.
You’re not over the hill, you’re just in the ’stationary phase’ of your growth.
Trying to leave work early? Tell your boss that due to the “high concentration” of employees, you’re “diffusing” out of the building and that attempting to stay would be “energetically unfavorable.”
Put “saccharides” in your coffee.
Try to “replicate your design information” with your significant other tonight.
While your at it, assure them that s/he has your “striated involuntary cardiac muscle tissue.’
Don’t touch anything today, but “probe” with your “receptors.”
Refer to household pets by using their binomial nomenclature, and don’t forget to refer to yourself as a “taxonomist.”
If you happen to be stacking objects today, make sure everyone knows that its a “nested hierarchy.”
Don’t forget to take it easy today. On Talk Like a Biologist Day, its important to “maintain homeostasis.”
Posted in evolution, humor, link out, microbiology | 6 Comments »
March 20th, 2008 ecoli
Helicobacter pylori is a fascinating bacteria with an interesting historical timeline. The Microbiology Blog ran a little segment on it, to announce an upcoming book, and I thought I’d add to the story.
Back in the days before 1979, stomach ulcers were blamed entirely on spicy food and stress. People that came down with ulcers or gastritis were put on a bland diet of oatmeal and soft foods like that.
Enter Australian pathologists, Robin Warren and Barry Marshall. They successfully isolated and cultured H. pylori from mucosal linings of the stomach specimens. They suggested that it was H. pylori in fact, and not diet, that was the direct agent of stomach ulcers and gastritis.
Initially, the response of the scientific community was skepticism. The consensus was that no organism could survive the high acidity of the stomach (pH 2). However, in an astonishing experiment, they proved the entire scientific community wrong.
Dr. Marshall drank H. pylori cultures, subsequently developing gastritis and the organism was recovered from his stomach lining. After ten days, an endoscopy was taken proving his symptoms were, in fact, gastritis and that H. pylori was present. He then treated himself with bismuth salts and Metronidazole, antibiotics to anaerobic organisms. They went on to show antibiotics as an effective treatment for many clinical cases of stomach ulcers.
To make the case even more interesting, in turned out, from later DNA sequencing data, this organism represented an entirely new genus of bacteria. Of which, several other species were discovered in other mammals and birds.
For their work and obvious dedication to ‘hands on’ experimentation, Warren and Barry received the 2005 Nobel Prize in medicine.
*disclaimer: drinking bacterial cultures will not necessarily garauntee a Noble Prize, though if you’re really desperate, it might be worth a try*
Posted in medicine, microbiology | 1 Comment »
March 18th, 2008 ecoli
Original ideas that categorized filamentous bacteria as the stressed and dying members of a population are apparently wrong. This is not a terribly unusual finding since scientists are always correcting ideas; assigning roles to presumably defunct systems and finding mechanisms for what were thought to be random processes.
Filamentation in bacteria occur when the cell continues to grow after its chromosomes have been copied, but the cell doesn’t divide. Filamentous cells are characterized by their elongated shape, which can be 10-50 times longer than normal. Certain bacteria have genes that encode proteins which can make alterations to cell length for the purpose of becoming filamentous, but random mutations can cause deletions in components controlling cell division with a similar affect.
Read the rest of this entry »
Posted in evolution, microbiology | No Comments »
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