As I am interested in things microbiological, I have been especially interested in the effect of breastmilk on the baby gut and gut microbiota. There have actually been quite a few studies on that, but most of these studies were about the gut microbiota only. However,  we can’t really separate our gut from the microbes that reside in it. The bacteria in the human gut affect the gut (and, in turn, the entire body) and are affected by it. The gut is really a superorgan, composed of a minority of human cells, and 10¹⁴ bacterial cells. Most of the gut is actually bacteria, not human, but the part that is human is important, since, well, it’s “us”. (Well, kinda hard to tell now which “us” is “us” and which “us” is “the bacteria that live in us”.) To understand what goes on there we need to study both bacterial and human cells. While adult microbiota+gut systems have been studied, mostly for the effect of probiotics, there have not been studies of baby guts because you cannot perform consented invasive procedures on babies. In other words, you cannot scrape their colons for gut lining, or epithelial, cells. So there has not been much of an opportunity to study the gut epithelium+microbiome in human infants.

The opportunity came with Robert (“Robb”) Chapkin from Texas A&M University, and Sharon Donovan from the University of Illinois at Urbana-Champaign. Robb has developed a system to isolate gut epithelial cells from the feces. We shed about millions of cells from our gut when we defecate, and Robb’s lab has a way to fish those gut lining cells out of the stool. Thus, we can sequence the mRNA, and find out which genes are transcribed in the baby gut. At the same time, we can analyze the baby’s microbiome. Enter Sharon Donovan’s lab, who has studied 12 babies,  six were breast fed and six were formula fed.

This is where Robb contacted me, and generously invited me to College Station, Texas about a year and a half ago. Aside from enjoying Texan hospitality (big steaks) and meeting people, Robb brought me into this fascinating study. They needed a bionformatician to help analyze the gut transcriptome and gut metagenome data. I am very glad they contacted me, since this started a very enjoyable collaboration and a scientific journey whose results are published this week  in Genome Biology. I was put in touch with two great statisticians, Ivan Ivanov and Scott Schwartz, also at Texas A&M. We put our heads together, and came up with  a strategy.

Analysis flowchart. Reproduced from Genome Biology 2012, 13:R32 doi:10.1186/gb-2012-13-4-r32 under BMC CC2.0 license. Click to enlarge.

First, we analyzed the microbiome data, using several standard pipelines, like MG-RAST for function analysis (thanks to the folks at Argonne National Lab and  for making MG-RAST happen  and for all their support) , and PhymmBL and GreenGenes for taxonomic analysis.  The gut transcriptome data were already available, as part of a previous study. Our next step was to look for correlations between the distribution of bacterial phyla in the babies, and whether the type of bacteria they had in their guts had anything to do with their diet.

So here is what we found. First, most breastfed babies had a greater variety of bacterial phyla between them than formula-fed babies. Probably because the formula babies were all fed the same diet, whereas breastmilk composition varies between women. Second, the breastfed babies were richer in gram negative bacteria. Those are bacteria with a thin cell wall, a double cell membrane, and which have certain features that the gram positives (thick cell wall, single membrane) do not have.  Also,  almost all breastfed babies had a richer gut ecosystem.

Firmicutes and Actinobacteria are gram+; Proteobacteria and Bacteroidetes are gram-. FF-formula fed babies, BF-breastfed babies. Genome Biology 2012, 13:R32 doi:10.1186/gb-2012-13-4-r32

We then moved on to look at the genetic potential of the gut microbiome: how do the microbial communities differ between the breastfed and bottle-fed babies in terms of what they can do. The strongest difference between breastfed babies and bottle-fed babies was in the presence of virulence genes, and mostly those typical of gram-negatives: Type III & IV secretion systems. There were other differences, such as in carbohydrate processing enzymes. But the kicker was that the differences in the frequency of virulence genes in the microbiome also correlated well with the expression of immunity related-genes in  the infant gut epithelial cells.

Reproduced from Genome Biology 2012, 13:R32 doi:10.1186/gb-2012-13-4-r32

Reproduced from Genome Biology 2012, 13:R32 doi:10.1186/gb-2012-13-4-r32

We observed the following: 1. Certain gram negative bacteria are dominant in the breastfed babies. 2. We saw that bacterial genes having to do with virulence were more abundant in the bacterial communities of breastfed babies 3. When looking closely at those genes, we saw that most of them were the virulence factors typical of gram negative bacteria (OK, not surprising given point[2] above, but a good verification). 4. At the same time, the breastfed babies expressed genes that had to do with immunity in their gut lining (epithelial) cells. The presence of virulence genes, and the expression of immunity genes in the gut epithelium correlated quite strongly (see B, below).

Reproduced from Genome Biology 2012, 13:R32 doi:10.1186/gb-2012-13-4-r32

Taken together, this tells us that the following scenario may apply: mother’s milk tends to enrich certain types of gram negative bacteria, and those, in turn, stimulate the babies’ immune system. It’s as if the mother’s milk is setting up an immunity boot camp for the breastfed babies.

We got all sorts of feedback and even a bit of media coverage on this study. I was really happy when this study hit Reddit. Reddit is an aggregation site where anyone can submit any kind of story, and the “redditors” vote it up or down. Highly voted submissions are more visible, and get discussed more on the site. Generally, having a submission receive many “upvotes”, in Reddit parlance, shows an interest. (Well, the highest upvotes tend to go to pictures of funny kittens, but still.) The story made it  to the top of the r/science category  (also known as “subreddit”) with over 1300 upvotes . I logged in using my real name, and referred people to another subreddit, called IAmA (“I am a…”). In this case “I am a scientist who worked on this study, ask me anything“. There were quite a few questions, and it was a very interesting engagement with people about this work. Hopefully, good PR and science communication.

Schwartz, S., Friedberg, I., Ivanov, I., Davidson, L., Goldsby, J., Dahl, D., Herman, D., Wang, M., Donovan, S., & Chapkin, R. (2012). A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response Genome Biology, 13 (4) DOI: 10.1186/gb-2012-13-4-r32

We have some really talented students in our department. And I don’t just mean the science. I am honored to present the colorful and hilarious microbial artwork of Amber Beckett. Created between gel runs at Natosha Finley’s lab:

Cereal Dilutions. Credit: Amber Beckett

Pepe the protein. Credit: Amber Beckett

StreptoCOWcus and Bortadella persussis. Credit: Amber Beckett

Prepared by daughter. Not to scale. Species not yet identified. Delicious.

Together with obesity, insulin resistance is the harbringer of metabolic syndrome. Insulin resistance is when the body cannot use insulin effectively. Insulin is needed to help control the amount of sugar in the body. As a result, blood sugar and fat levels rise.  Therein lies the path to morbid obesity, diabetes, stroke, and heart problems.

So what’s the connection of metabolic disease to bacteria? Well, for one thing, we know that in obese people the bacterial population in the gut is different, and the different population of bacteria may lead to a vicious cycle contributing to obesity.

Another possible connection has to do with an  important group of molecules in our body called Toll-like receptors, or  TLRs. TLRs are a family of  membrane proteins that sense a wide variety of bacterial populations and activate our innate immune system. TLRs are like a first-defense warning station: they sense the bacterial enemy first, and, if needed, activate the proper defense mechanisms. Researchers studying TLR-2 have created knockout mice lacking TLR-2, and they discovered is that many of TLR-2 knockout mice do not develop insulin resistance when fed with a high-fat diet. Think about it: all the McCrap you can eat, yet your blood sugar level remains normal (although you still grow fat).  So why does that happen? How come these mice lacking a bacterial sensor also seem immune to insulin resistance?

To answer this, we must understand that TLR receptors (quite a few are known so far) are known to serve as a bridge (or “mediate crosstalk”) between the immune system and the body’s metabolism.  Mice without TLR-5 develop eating disorder known as hyperphagia which is characterized by an increased appetite; they also show other pre-diabetic  symptoms: hypertension, high lipids, and insulin resistance. I have posted before about how TLR-5 may control the type of gut bacteria mice have and, in turn, control their propensity for obesity.

TLR-4 deficient mice, on the other hand, seem to be protected from insulin resistance, just like TLR-2 deficient mice. So a connection between these front-line sensors of the immune system and whole body metabolism is well-known.

A group of researchers from Brazil have decided to look further into these “diabetes resistant” mice. The thing about mutant TLR deficient mice, is that they are normally grown in sterile conditions because possible infections and because the uncontrollable gut microbes add uncontrolled variables to any experiment. When scientists cannot precisely control for experimental conditions, they face two choices: One, they can deviate from the model to emulate “real world” better, but sacrifice control of one or more of the variables in an experiment. Or, maintain full control of the experiment and sacrifice a simulation whatever they are trying to model. Most scientists go with the second option: they would prefer to have a well-controlled model, even if it supposedly detracts from its supposed practicality and application to “real life”. That is because a model (in our case, mutant TLR mice), is somewhat removed from the real thing anyway: mutant TLR-deficient are basically a  an artificial construct used to investigate the effect of knocking out a TLR from the mouse, so hopefully we can draw conclusions about humans. So the second type of possible error is the one scientists generally prefer to make.

Toll-like receptors: it's complicated.

But Andrea Caricilli and colleagues have decided to look at TLR-2 knockout mice in non-sterile conditions. Rememebr: TLR-2 knockouts seem to have protection from insulin resistance. What Caricilli and her colleagues discovered was quite the opposite of what was known so far: TLR-2 knockout mice were not protected from insulin resistance. Quite the opposite: the mutant mice developed metabolic syndrome. But did  the gut bacteria do it? To check that, the researchers treated the mice with broad-spectrum antibiotics for 20 days. After that, the bacterial species that re-colonized the mice’s guts were quite different in their composition from the bacterial species that originally inhabited them. And they did not have meteabolic disease, or the symptoms were much less severe.

So here it is: changing the mice’s gut microbiota changed them from mice with insulin resistance to mice without insulin resistance. Yes, there are mutant mice, but still: insulin resistance was turned off  by changing the types of microbes in the gut.

They then transplanted the microbiota from TLR-2 mutants which had insulin resistance to regular mice. And what do you know: the regular mice then showed symptoms of insulin resistance and metabolic disease.

There is a lot more to this paper than these two experiments: they have also investigated many other parameters, trying to come up with the chain of events that bacteria trigger when causing metabolic disease. I won’t get into that, the paper is quite long with some 20(!)  figures. A lot of work went into this. But the bottom line again supports what has been shown in other studies: the bacteria that live in our gut are responsible for our metabolism, and it is the interaction between the bacteria and our immune system that not only protects us from pathogens, but also protects us (or not) from metabolic disease.

 Update: this post has been slashdotted. Exercise extreme caution.

Caricilli, A., Picardi, P., de Abreu, L., Ueno, M., Prada, P., Ropelle, E., Hirabara, S., Castoldi, A., Vieira, P., Camara, N., Curi, R., Carvalheira, J., & Saad, M. (2011). Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice PLoS Biology, 9 (12) DOI: 10.1371/journal.pbio.1001212

 

The Dead Body That Claims It Isn’t: I’m not dead.
The Dead Collector: What?
Large Man with Dead Body: Nothing. There’s your ninepence.
The Dead Body That Claims It Isn’t: I’m not dead.
The Dead Collector: ‘Ere, he says he’s not dead.
Large Man with Dead Body: Yes he is.
The Dead Body That Claims It Isn’t: I’m not.
The Dead Collector: He isn’t.
Large Man with Dead Body: Well, he will be soon, he’s very ill.
The Dead Body That Claims It Isn’t: I’m getting better.
Large Man with Dead Body: No you’re not, you’ll be stone dead in a moment.

– Monty Python and the Holy Grail

So it goes between John Cleese, Eric Idle and John Young.

But there is a sea, or rather lake, that is not dead yet either, feels happy, and is going for a walk on Thursday. The Dead Sea, located in the Judean Desert, roughly divided between Jordan and Israel, has a salinity of 33% – more than eight times that of seawater (3.5%). No animals or plants can survive these conditions, and the lake does look dead to the casual observer. But in the late 1930s Benjamin Elazari Volcani discovered that the Dead Sea does, in fact, support several types of microorganisms. A bit of history: Volcani’s research into microbial life in the Dead Sea led to him being awarded the the first doctoral degree in microbiology by the Hebrew University of Jerusalem, 1943. In 1975, Mullakhanbhai and Larsen named Halobacterium volcanii, a halophilic isolate, after B.E. Volcani. It is now know as the archaean, not bacterium, Haloferax volcanii.

At 33% salinity we all float. When you're down here with us, you'll float too.

Several other archeael isolates were found, noting that the Dead Sea is not quite dead yet. In fact, the lake sports what might be an underreported biodiversity. In addition to archaea it also has fungi, bacteria, protozoa and mermaids. OK, maybe not mermaids.

Now the Dead Sea has been found to be more alive than ever. A groups of Israeli and German divers have found freshwater springs deep in the Dead Sea. The springs are about 30m deep, and lie in of large craters 30meters in diameter. Look at the video below, taken by the divers. Between 1:54 and 2:10 you can see the freshwater mixing with the saltwater. The stark differences in salinity makes for a surreal underwater smoke effect. And, the real kicker, at 2:26 you can see a thick microbial mat, like gunk all over the rocks near the spring.

It would be very interesting to find out who, exactly, comprises this mat. As far as I know, this analysis has not been published yet. But the initial results are reported in National Geographic:

Preliminary analyses of samples collected in the craters suggest that the springs’ bacterial communities are very diverse—akin to what you’d find living on rocks in a regular saltwater sea, he added.

The top of the springs’ rocks are covered with green biofilms, which use both sunlight and sulfide—naturally occurring chemicals from the springs—to survive. Exclusively sulfide-eating bacteria coat the bottoms of the rocks in a white biofilm.

Not only have the organisms evolved in such a harsh environment, Ionescu speculates that the bacteria can somehow cope with sudden fluxes in fresh water and saltwater that naturally occur as water currents shift around the springs.

All I can say is: wow. Microbial mats in the Dead Sea, which we only find about now. The  Dead Sea thriving with whole carpets of life. Who’d've thunk?

ELAZARI-VOLCANI, B. (1943). Bacteria in the Bottom Sediments of the Dead Sea Nature, 152 (3853), 274-275 DOI: 10.1038/152274c0

Mullakhanbhai, M., & Larsen, H. (1975). Halobacterium volcanii spec. nov., a Dead Sea halobacterium with a moderate salt requirement Archives of Microbiology, 104 (1), 207-214 DOI: 10.1007/BF00447326

Buchalo, A., Nevo, E., Wasser, S., Oren, A., & Molitoris, H. (1998). Fungal life in the extremely hypersaline water of the Dead Sea: first records Proceedings of the Royal Society B: Biological Sciences, 265 (1404), 1461-1465 DOI: 10.1098/rspb.1998.0458

Press Release
2011-10-03
The Nobel Assembly at Karolinska Institutet has today decided that
The Nobel Prize in Physiology or Medicine 2011
shall be divided, with one half jointly to
Bruce A. Beutler and Jules A. Hoffmann
for their discoveries concerning the activation of innate immunity
and the other half to
Ralph M. Steinman
for his discovery of the dendritic cell and its role in adaptive immunity

(Unfortunately, Steinman died between the committee’s decision and the announcement. He still received the Prize, though.)

However, it is not news (and not good)  that we are losing the arms race against bacteria. We are overusing antibiotics in medicine and in agriculture, virtually nurturing today’s and tomorrow’s killers. A report  in Wired earlier this year paints a bleak picture:

Truly new antibiotics are critically needed because bacteria, having no experience of them, cannot immediately mount resistance to them — something that does happen with me-too compounds featuring some slight molecular change. But they’re rare. As this chart from the research group Extending the Cure shows, antibiotic development has slowed dramatically over the past 30 years, and among the few drugs being brought forth, most share the mechanisms of already-existing classes.

To understand the extent of the crisis, we have to remember that antibiotics are the foundation of a huge number of  medical procedures, from cancer treatment to dentistry. Taking away this foundation would cripple modern medicine. Together with vaccines and public hygiene, antibiotics are the reason that many of us live longer — and better — than our grandparents’ generation and before that.

So lacking drug company motivation (more on that in McKenna’s report) and facing a dwindling supply of effective antibiotics, what are we to do?

A good start is to take a second look at nature. For example, here is a Kangaroo being born:

Awww…

The interesting thing about Kangaroos and other marsupials is that their young are being exposed at a very precarious stage to the outside world. Roo is born in a fetal state: underdeveloped, blind, barely moving and has little to no body temperature regulation. All of these problems are taken care of by Kanga’s protecting Roo’s six minute trip to her pouch where things are warm and cozy, and maternal milk flows in abundance. All except one: pathogens. During his trip, Roo can acquire a whole bunch of nasty bugs from Kanga’s fur and the air. Also, the pouch is not exactly a sterile environment and there is a possibility of infection there. So how is little Roo to survive the trip to the pouch and subsequent stay?

Joey in pouch. Photograph by Geoff Shaw (Zoology, University of Melbourne, Australia). From Wikimedia Commons.

The answer is innate immunity, that collection of mechanisms which protect the host in a non-specific manner. While his adaptive immunity is quite undeveloped, Roo does produce some killer all-purpose peptides he can use against microbes. The same class of peptides are produced in Kanga’s milk. Collectively they are known as cathelicidins. Only about 30 amino acids long, these highly charged molecules kill both gram-positive and gram-negative bacteria.

Since the tammar wallaby genome has recently been sequenced,  a group of Australian scientists has decided to hunt for cathelicidins in the tammar’s genome. They also looked for cathelicidins in the genomes of the duck-billed platypus (a monotreme) in the opossum (an American marsupial), in human, mouse, cow & sheep (all placentals).  Here is what they found. Each leaf on the tree represents a cathelicidin gene. The leaf colors and shapes are for different species of origin.

From Wang J, et al. 2011 PLoS ONE 6(8): e24030. doi:10.1371/journal.pone.0024030 Reproduced under CC license.

The marsupials and monotremes have a much higher diversity of cathelicidin genes than the placental mammals. Note that there are many duplicates of the cathelicidin gene in Pig and Cow, but these duplications are very recent as we can tell by the highly similar sequences of the genes. These duplications are probably because herd animals are more susceptible to pathogens.  In any case,  pig and cow have higher copy number of cathelicidin genes, and thus perhaps a large number of proteins, but not many different ones as in marsupials and monotremes. Diverse cathelicidin genes in the genome can offer a wider protective umbrella against many different types of pathogens.

Back to the antibiotic crisis: can we use marsupial cathelicidins as an antibiotic in humans? Do cathelicidins kill human pathogens? Are they toxic to humans? The authors checked the first two. They used cathelicidins from wallaby and platypus to kill human pathogens: P. aeruginosa, K. pneumoniae and A. baumanii, including antibiotic resistant strains. Cathelicidins were much more effective than, well, antibiotics against those bacteria. Also, cathelicidins did not kill human red blood cells, which makes them a potential drug. Of course,  immune reaction against cathelicidins as a foreign  still needs to be checked, among many, many other things, but the whole idea of looking at marsupials is that, as mamals, they may be able to supply us with clues on how to synthesize a cathelicidin to be used as a drug in humans.

The really cool thing about this study is that the authors used phylogenetics to design an ancestral wallaby cathelicidin. They aligned all the wallaby cathelicidin protein sequences, which were conserved in 40 of the 46 amino-acid positions. They used PAML, GASP and Ancescon to reconstruct an ancestral wallaby sequence, estimated to be 59 million years old, marked by an asterisk (*) in the above gene tree.  They then synthesized the ancestral WAM (Wallaby Anti Microbial) peptide and used it to kill bacteria. Guess what: the ancestral WAM was even better than the existing WAMs, as even a lower concentration was needed to kill bacteria. They are still working on red blood cell toxicity (yay for PLoS-enabled comments!)

So maybe the answer to  the increase in bacterial resistance to antibiotics lies in Kanga’s pouch. After all, she was very protective of Roo.

EDIT: clarified that the part about synthesizing and testing ancestral-WAM to kill bacteria.

Wang, J., Wong, E., Whitley, J., Li, J., Stringer, J., Short, K., Renfree, M., Belov, K., & Cocks, B. (2011). Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options PLoS ONE, 6 (8) DOI: 10.1371/journal.pone.0024030

Tonight is Shavuot. That wonderful holiday which includes midnight studies, water-bombing and dairy products. Mmmmm…. cheese. A food product heavily embedded in the science of microbiology. Cheese is the founding product of the biotech industry (along with beer and bread).

Boaz asking Ruth on a date to the cheese and wine festival.

So here’s to Lactobacilli and Lactococci which are at the center of the production of dairy products. Breaking down milk sugar (lactose) into lactic acid, which curdles the milk protein casein.   Left to its own devices, this process generally produces rotten milk, since other bacteria may join the fray. Cheesemaking starts the process by  adding some rennet first. Rennet was originally and still being produced from cows’ upper stomachs. The active ingredient in rennet is chymosin, used to curdle milk drunk by calfs.  But 90% of  cheeses produced in the US and the UK now are made using recombinant chymosin,  produced in the fungus Aspergillus niger.

Lactobacillus sp. Source: wikipedia

Cheese also needs to ripen. Propionibacterium freudenreichii ferments lactate in the cheese to produce, among other things, carbon dioxide. This produces the holes we see in Swiss cheese. But it’s a finicky bug, and needs its faithful symbiotic companion Lactobacillus helveticus (“Swiss Lactobacillus“) to provide it with essential amino acids necessary for its growth.  P. freudenreichii is named after Eduardo von Freudenreich, a 19th century microbiologist who, among other things, wrote a seminal book on dairy microbiology.

Some cheeses are somewhat riper than others, as Asterix, Obelix and Dogmatix discover.

By the way, Propionibacterium acne a relative of Propionibacterium freudenreichii is a bacteria found on our skin which at times causes… yes, acne. But don’t think about acne when you eat Swiss cheese. (Now I put some people off Swiss for quite a while).

"Acne" comes from "acme" which means point, edge or peak. Here is an acme, but not acne.

Finally, mold. Penicillinum roqufortii provides those beautiful blue streaks in the sheep-milk cheese Roquefort… and the taste. Only cheeses aged in the natural Combalou caves of Roquefort-sur-Soulzon may bear the name Roquefort. Which is why it is so damn expensive.

And I haven’t even started upon Camembert (the real one is made from unpasteurized milk) ripened by  Penicillium candidum and Penicillium camemberti. Or kefir, made from the eternal Kefir grains, a matrix of bacteria and polysaccharides  that can be reused forever…. but I’m too hungry for cheesecake to continue this.

EDIT: typos. Thanks Martin!

Not a cell wall

So, for example, when I am developing computational metagenomics analysis tools, they invariably tend to target both bacteria and archaea. However, these tools are usually not good for microbial eukaryotes, due to different rRNA size, the larger genomes with more non-coding regions, lack of operons, organelles genomes, introns, etc. So for this utilitarian purpose, “prokaryotes” would be a good verbal shortcut to the cumbersome “bacteria and archaea” when describing or documenting the software. So can we all agree on “prokaryotes” as a verbal shortcut of necessity but not as a taxonomic definition? Or am I missing something substantial here?

An illustrative example of the rational, cool-headed debate that may ensue:

Herpetology Credit: xkcd.com

Miami University has  joined the National Genomics Research Initiative (NGRI) offered by HHMI Science Education Alliance (SEA) in their Phage Genomics course. The students go directly into the lab, participating in an authentic research experience. In a full-year academic course they:

• isolate and characterize bacterial viruses from their local soil
• prepare the viral DNA for sequencing
• annotate and compare the sequenced genome

The Department of Microbiology at Miami University is offering this course in the upcoming year: four of our faculty will be teaching it. Phage isolation, electron microscopy, DNA sequencing in the first semester, annotation and comparative genomics in the second. And I get to teach the bioinformatics bit: annotation and comparative genomics. Woo-hoo! The great thing about this course, is that unlike most lab courses, the students (and faculty) will be setting up experiments intended not only to teach, but also to discover something new.  Also, the results of the research are meaningful. Genomics data generated by student participants will be used by other researchers to answer medical, ecological, and evolutionary scientific questions. Bacteriophages (viruses that infect bacteria) affect the biopsphere so profoundly, it is almost impossible to imagine. Their sheer biomass is equal to that of 75 million blue whales, and marine bacteriophages  kill about half of marine microbes every day. Bacteriophages have a huge host range, mind-boggling number of particles in the biosphere (10³⁰) and, above all, the genetic diversity is unmatched by all other life combined. Participating students will see how their data may be used by other researchers in the SEA network — truly collaborative, crowdsourced science. Here are the genomic sequences of SEA-sequenced bacteriophages already in GenBank.

If you are an incoming Miami freshman, and want to jump in and do some real science, it doesn’t get much better than this. Check out our course page, and ask about the Bacteriophage Biology course in your orientation. You may even get your name on a paper like these students from other participating universities.

Pope, W., Jacobs-Sera, D., Russell, D., Peebles, C., Al-Atrache, Z., Alcoser, T., Alexander, L., Alfano, M., Alford, S., Amy, N., Anderson, M., Anderson, A., Ang, A., Ares, M., Barber, A., Barker, L., Barrett, J., Barshop, W., Bauerle, C., Bayles, I., Belfield, K., Best, A., Borjon, A., Bowman, C., Boyer, C., Bradley, K., Bradley, V., Broadway, L., Budwal, K., Busby, K., Campbell, I., Campbell, A., Carey, A., Caruso, S., Chew, R., Cockburn, C., Cohen, L., Corajod, J., Cresawn, S., Davis, K., Deng, L., Denver, D., Dixon, B., Ekram, S., Elgin, S., Engelsen, A., English, B., Erb, M., Estrada, C., Filliger, L., Findley, A., Forbes, L., Forsyth, M., Fox, T., Fritz, M., Garcia, R., George, Z., Georges, A., Gissendanner, C., Goff, S., Goldstein, R., Gordon, K., Green, R., Guerra, S., Guiney-Olsen, K., Guiza, B., Haghighat, L., Hagopian, G., Harmon, C., Harmson, J., Hartzog, G., Harvey, S., He, S., He, K., Healy, K., Higinbotham, E., Hildebrandt, E., Ho, J., Hogan, G., Hohenstein, V., Holz, N., Huang, V., Hufford, E., Hynes, P., Jackson, A., Jansen, E., Jarvik, J., Jasinto, P., Jordan, T., Kasza, T., Katelyn, M., Kelsey, J., Kerrigan, L., Khaw, D., Kim, J., Knutter, J., Ko, C., Larkin, G., Laroche, J., Latif, A., Leuba, K., Leuba, S., Lewis, L., Loesser-Casey, K., Long, C., Lopez, A., Lowery, N., Lu, T., Mac, V., Masters, I., McCloud, J., McDonough, M., Medenbach, A., Menon, A., Miller, R., Morgan, B., Ng, P., Nguyen, E., Nguyen, K., Nguyen, E., Nicholson, K., Parnell, L., Peirce, C., Perz, A., Peterson, L., Pferdehirt, R., Philip, S., Pogliano, K., Pogliano, J., Polley, T., Puopolo, E., Rabinowitz, H., Resiss, M., Rhyan, C., Robinson, Y., Rodriguez, L., Rose, A., Rubin, J., Ruby, J., Saha, M., Sandoz, J., Savitskaya, J., Schipper, D., Schnitzler, C., Schott, A., Segal, J., Shaffer, C., Sheldon, K., Shepard, E., Shepardson, J., Shroff, M., Simmons, J., Simms, E., Simpson, B., Sinclair, K., Sjoholm, R., Slette, I., Spaulding, B., Straub, C., Stukey, J., Sughrue, T., Tang, T., Tatyana, L., Taylor, S., Taylor, B., Temple, L., Thompson, J., Tokarz, M., Trapani, S., Troum, A., Tsay, J., Tubbs, A., Walton, J., Wang, D., Wang, H., Warner, J., Weisser, E., Wendler, S., Weston-Hafer, K., Whelan, H., Williamson, K., Willis, A., Wirtshafter, H., Wong, T., Wu, P., Yang, Y., Yee, B., Zaidins, D., Zhang, B., Zúniga, M., Hendrix, R., & Hatfull, G. (2011). Expanding the Diversity of Mycobacteriophages: Insights into Genome Architecture and Evolution PLoS ONE, 6 (1) DOI: 10.1371/journal.pone.0016329