E. coliImage credit

A bacterium’s fight against antibiotics seemed to pit each individual prokaryote against the world. If the bacterium had the gene(s) to neutralize the antibiotic, it survived. If it didn’t have those genes, bye-bye bacterium. Whether this bacterium’s neighbor was susceptible or not wasn’t thought to matter.

Research published in today’s Nature shows that antibiotic resistance isn’t so singular. The team led by James Collins found that a single colony of E. coli contains bacteria with differing levels of antibiotic resistance. What’s more, those bacteria that had the stronger resistance seemed to protect the rest of their less resistant colony members from the effects of the antibiotics, even though it came at a cost of fitness to the super-resistant bacteria.

A pure colony of bacteria is essentially a group of clones. In theory, a colony of bacteria is descended from a single bacterium. Because bacteria reproduce by dividing into two identical cells, the colony consists of millions of genetically identical individuals. Mutations can and do occur, and so even bacteria within the same colony can vary slightly. However, two bacteria from Colony A likely have more in common genetically than two bacteria in Colony B. Thus, a “colony” of bacteria could also be conceived of as the equivalent of a family unit.

Collins’ group grew E. coli in a large container called a bioreactor, which allows the researchers to precisely control the bacteria’s environment (and Collins says looks like “a component of a moonshine factory out in the backwoods.” )  They first added the minimum amount of the antibiotic norfloxacin that would inhibit bacterial growth. The researchers took a sample of bacteria every 24 hours, spread the liquid on a petri dish, grew up the bacteria and measured the antibacterial resistance of 12 randomly selected colonies.

Molecular structure of indole

Most of the bacterial colonies had lower antibacterial resistance than the entire system grown in the bioreactor. A few colonies, however, had a much higher bacterial resistance than average. These highly resistant bacteria had high levels of the enzyme tryptophanase, which E. coli uses to synthesize indole. A signaling molecule produced during times of high stress, indole can trigger a bacterium to turn on tiny pumps that remove the norfloxacin from within the cell. Indole can also prevent bacteria from being harmed by the high levels of free radicals created during antibiotic treatment.

The highly resistant bacteria synthesized extra indole not for their own benefit, but for the benefit of other colony members.  Collins hypothesizes that this is a type of “kin selection,” where an organism acts to protect those who share the same genes, even at high cost to the organism. Because the E. coli in the bioreactor were grown from a single colony, their descendents are essentially one big happy family.

Because so many bacterial species produce indole, Collins thinks that targeting indole signaling might be a new path to create new antibiotics.

These gigantic, flightless birds roamed South America during the Cenozoic (62-2 million years ago) before ultimately going extinct. The birds had large skulls and massive beaks, standing between 1-3 meters in height. Andalgalornis was a mid-sized terror bird, about 1.5 meters tall and weighing about 45 kg. Although paleontologists knew terror birds were carnivorous, no one knew exactly how they killed their prey.

A group of scientists led by Federico Degrange of the Universidad de la Plata in Argentina analyzed a fossilized skull of A. steulleti, which lived in Argentina approximately 6 million years ago. A CT scan revealed an unusually thick and rigid skull, which gave the skull much more strength in the front-to-back direction. Instead of being light and flexible like most bird skulls, the joints in the Andalgalornis skull were fused together into rigid beams that provided extra strength. This strength was not matched in the left to right direction or the up and down direction, which led the researchers to believe that this bird wasn’t engaging in any mad fights with their prey as their skulls and beaks weren’t strong enough to withstand any risky moves.

Artist's rendering of Andalgalornis attacking its prey. By Marcos Cenizo.

In an interview with Wired magazine, co-author Lawrence Witmer said “CT scanning extinct animals is exciting because you never really know what you’ll find inside. But you don’t need a CT scan to tell that this was one huge, bad-ass bird.”

Indeed, Dr. Witmer. Indeed.

Degrange FJ, Tambussi CP, Moreno K, Witmer LM, Wroe S (2010) Mechanical Analysis of Feeding Behavior in the Extinct “Terror Bird” Andalgalornis steulleti (Gruiformes: Phorusrhacidae). PLoS ONE 5(8): e11856. doi:10.1371/journal.pone.0011856

On Earth, biomolecules such as amino acids and sugars have different handedness; that is, the molecules can be mirror images of each other.  With the two amino acids in this picture, you can kind of imagine a mirror in between the two of them.  Yet no matter how you flip them around, the hydrogen atom and the amino group will not match up. Chemically, these compounds are exactly the same.  If you ran the same chemical reactions side by side, you wouldn’t be able to tell the difference.  However, the enzymes in your body are a little more discerning.  They only like the left-handed alanine molecule (on, ironically enough, the right-hand side of the image).  The D-alanine molecule?  The enzymes couldn’t be bothered.

 With sugars, the enzymes prefer the right-hand stereoisomer.

Why?  There’s a lot of hand-waving that goes along with those answers.  What many scientists think is that it was likely just some of the chance happenings that occur with natural selection.  As far as any biochemists know, there is no biological reason one stereoisomer should be preferred more than any other.  And when experiments have been done to try and create biomolecules in “primitive earth” conditions, there has been no selectiveness in terms of isomers.  Both left-handed and right-handed molecules were produced in a 50:50 ratio.

The researchers who wrote this paper, however, have a different theory.  They believe that the selectiveness of the isomers might have been due to the molecules that arrived on meteorites and other debris from outer space.

On meteorites, there are relatively large numbers of aldehyde molecules (like formaldehyde from your biology dissection labs- the fumes always made me throw up).  The researchers found a “pristine meteorite” in Antarctica and analyzed some of the carbon-based molecules on it.  They looked at two amino acids- alloisoleucine and isoleucine, which are mirror images of each other, and found that their precursor molecules — the aldehydes — were likely not in a 50:50 ratio of stereoisomers.*  In fact, they found a 14% excess of the left-handed aldehydes.

This paper, like any research paper should, raises more questions than it answers.  What is a pristine meteorite and how can we tell?  Are these good ways to look for biomolecules?  What does this tell us about how life may have started?  Could the excess of the left-handed isomers be a fluke?  Does this make life from outer space any more or less likely?  Does life have to have left-handed amino acids and right-handed sugars?

And for further reading, check out Robert Hazen’s book Genesis.  Don’t worry, it’s not religious at all.

I can’t get the DOI information right now- I’m working on it.  I’ll post it as soon as I get it! Image credit: Tainano Nanobiotechnology Glossary *Fun chemical vocabulary: racemization (ray-SUH-muh-zay-shun) is when you start out with an excess of one stereoisomer, and over time, it turns into a 50:50 ratio.

Researchers at the University of Michigan and at the National Institute on Aging conducted a detailed study of genetic variation in human populations, which can pinpoint a person’s genetic heritage to a specific population in a geographic region.  Results at this level of specificity mean that this information is 100 times more detailed than previous studies.

Data was gathered from 29 populations on five contients, and a total of 500,000 different genetic markers were sequenced.  What the data showed was the continual implications of the founder effect, which happens when a small, random subset of a population leaves the main group and reproduces on their own.  Because these founder populations are usually so small — sometimes less than 50 people — a mutation that was initially rare in the larger group can become quite frequent in the founder population.  So as small groups of humans broke off from the larger population to settle in new areas, the diversity of the group was gradually diminished.

“Now that we have the technology to look at thousands, or even hundreds of thousands, of genetic markers, we can infer human population relationships and ancient migrations at a finer level of resolution than has previously been possible,” said lead co-author Noah Rosenberg, of the University of Michigan’s Life Sciences Institute, in a press release.

From a genetics standpoint, what is especially interesting is the importance of copy number variants (CNV) in DNA.  CNVs are long stretches of DNA that can be repeated in different numbers in different people- or deleted entirely.  Some genetic diseases, like Fragile X Syndrome, are caused when the copies of a particular DNA sequence get so large that they cause structural abnormalities.  With an additional 507 CNVs discovered by Rosenberg’s group, researchers now have more tools to use to screen for potential genetic diseases.

“This data set is so rich. It provides a much more comprehensive, cross-sectional snapshot of the human genome than previous studies,” said Paul Scheet, a post-doctoral researcher in the U-M Department of Biostatistics and one of the lead authors.

Some information and quotes provided by University of Michigan press release.

Jakobsson, M., Scholz, S.W., Scheet, P., Gibbs, J.R., VanLiere, J.M., Fung, H., Szpiech, Z.A., Degnan, J.H., Wang, K., Guerreiro, R., Bras, J.M., Schymick, J.C., Hernandez, D.G., Traynor, B.J., Simon-Sanchez, J., Matarin, M., Britton, A., van de Leemput, J., Rafferty, I., Bucan, M., Cann, H.M., Hardy, J.A., Rosenberg, N.A., Singleton, A.B. (2008). Genotype, haplotype and copy-number variation in worldwide human populations. Nature, 451(7181), 998-1003. DOI: 10.1038/nature06742

However, in the most recent edition of PLoS Pathogens, researchers from the University of Georgia and the University of Montana (among others) released a ground-breaking study on Apicomplexa biology.  Hadn’t heard of Apicomplexa?  Neither had I.  But they are a phylum that consists of many of the parasites that have plauged humans for millennia, such as Toxoplasma gondii, Cryptosporidia, and Plasmodium sp., the latter of which cause malaria in hundreds of millions of people each year.  Studying these little critters has been difficult first because, being eukaryotes, they have substantially more genes than bacteria or viruses.  Second of all, drug development has been hindered because, again, they’re eukaryotes.  Things that kill them are much more likely to kill or harm us.

When you add all of these factors to the historical deficits in funding towards tropical disease (read as: diseases that don’t affect Americans and therefore effectively don’t exist), it meant that little progress was being made towards finding new cures for malaria and like diseases.

Enter the current study on Aplicomplexa.

What these scientists did was take a first step in developing a more firm understanding of parasite biology.  Many of these genomes have been sequenced.  And, like with the Human Genome Project, it’s a fantastic first step.  But only a first step.  Information isn’t all that useful until you can, I don’t know, actually use it.  The biologists involved with this study created a high-throughput genetic screening for heat-sensitive Toxoplasma gondii mutants.

Which means precisely nothing, until you understand that “high-throughput genetic screening” really means an easy way to look at a lot of different genetic sequences really really quickly, and that heat sensitivity is really just a way for scientists to identify mutations that might be involved with cell replication and development.  Using a technique called “forward genetics,” the researchers first generated thousands of mutant Toxoplasma cells, each with a potentially different mutation affecting their growth and development.  Then, using the high-throughput screening method, these genes were identified and paired with the mutation.

This isn’t a cure-all by any means.  Drug development is still years, if not decades, down the road.  But a basic understanding of the Toxoplasma cell machinery has been greatly improved, and with this step, drug development can move forward.

You can find the full text of the article here: Forward Genetic Analysis on the Apicomplexan Cell Division Cycle in Toxoplasma Gondii.

My redeeming point is that I have been busy. 
My non-redeeming point is that I haven’t been that busy.

I am starting work on my thesis, a little 40 page ditty on the factors that are causing the epidemic spread of the Chikungunya virus, which means I am going to be having to give up my little pet stories for class on random science topics until May.  Which made me think of this blog (again), and how it would be a perfect home for all of my random drivel.

So I’m back, and looking forward to writing with much greater consistency and quality than before.  Not that three posts, one of which was a cartoon, is much to talk about.  Still, a girl can dream.

A dramatic view of why smoking gives you cancer.


Still Smoking? Watch This !! – video powered by Metacafe

When I was a student at the School of Public Health at the University of Michigan, there were always a few students in every class who continued to smoke. I understand addiction in my own little way, but still. When the first example in your epidemiology class is working on the stats of lung cancer and smoking, it made me wonder if they should flunk that class. Just, you know, on the spot.

The link comes by way of Scientist, Interrupted (Living the Scientific Life).

The idea that bacteria could cause the deterioration of paintings was hardly new; in fact, lithotrophs (bacteria that can use inorganic compounds, such as iron and sulfur) have been used to aid the restoration of paintings.  Given the location of the painting within the cathedral, the scientists hypothesized that the contamination was microbiological rather than chemical. They took a sterile scalpel and scraped a tiny bit of the discolored paint off of the fresco- approximately 1 mm square.  They amplified any bacterial DNA using PCR, focusing in on the 16S rRNA genes.  Since each species of bacteria has a distinct 16S rRNA gene, identification would be fairly straightforward.  Portions of the gene were sequenced, and the bacteria were identified using a BLAST search.  The predominant species of bacteria was Rubricobacter radiotolerans.  Quantitative PCR found species from Archaea to be a minority of the species found in the discolored areas. Raman spectroscopy (as opposed to the better known Ramen Noodle Soup, staple of poor college kids) was used to confirm the identity of the bacterial species.  A sample of the discolored paint was compared to a pure colony of Rubricobacter radiotolerans, which provided an almost exact match.

Rubrobacter radiotolerans shows the characteristic reddish pigmentation due to the presence of two main C-50 carotenoids, namely bacterioruberin and monoanhydrobacterioruberin…

The specific color spectrum of these bacterial pigments matched the color spectrum of the discoloration of the fresco on the “The Crypt of the Original Sin.”  The authors of the study believe that an abnormally hot and dry “spring-summer period,” along with restoration efforts that increased daylight UV rays, may have “promoted the outgrowth of xerotolerant heterotrophic bacteria, primarily Rubrobacter spp., at the expenses of the preexisting microbial community.”

Source: Imperi F, et al.  “The bacterial aetiology of rosy discoloration of ancient wall paintings.”  Environmental Microbiology, 2007, 9(11), 2894-2902.

 Hence the situation in the comic.