Lab happenings, food, and sites in Krakow, Poland

The International Symbiosis Society 7th Congress is coming to a close. Below are a handful of pictures that Im fond of and will hopefully inspire you to get to Krakow one day. It is a beautiful, lovely, and cozy city. Also very cheap.

The Royal Castle on Wawel Hill in the distance. One of the great symbols of Polish statehood. The former capital and seat of kings as well as the place of their coronation and burial.

Squint and you may see a walking beer holding a stop sign. Inquiring minds want to know more.

The tower is what's left of the old town hall in the Market Square of Krakow.

The biggest square in Europe and Krakow's elegant showpiece.

What the town hall looked like in its completeness. Only the tower in the pictures above remains standing today.

An Espresso Lunch at Hotel Francuski, recommended by a friend of my student. For $6 USD, this was a steal. Freshly squeezed juice, cabbage, ribs, potatoes, and rugula cake.

 Senior graduate student, Rob Brucker, giving his talk on "Gut Bacteria Enhance Postmating Reproductive Isolation"

Perhaps the best chicken cesar salad Ive ever had.

Group picture of Lisa, me, Rob, and Jason in front of Lisa's poster "Mom knows best: Maternal regulation of Wolbachia titers"

I'll add just one scientific thought to this post. This meeting has convinced me more than ever that we live in an age where symbiosis is a centerpiece to Biology in the 21st century. A profound, modern synthesis is underway in which the century old merger of evolution and genetics is being updated with symbiosis as the third pillar.

My talk at the International Symbiosis Society Congress 2012

The International Symbiosis Society is now meeting in Krakow, Poland. About 300 participants have gathered to discuss their latest research, meet colleagues, and form new collaborations. Here is my talk from yesterday's session on Horizontal Gene Transfer and the Role of Viruses:

The Entangled Bank in Animals: Viral Transfer Between Bacterial Symbionts

Note 1: the recording starts on the second slide of the talk
Note 2: Related blog post at http://symbionticism.blogspot.com/2012/06/universality-and-complexity-of-viruses.html

In this talk at the International Symbiosis Society Meeting in Krakow, Poland, 2012, I discuss the transfer of genes between bacterial coinfections in animal hosts. Animal species are a conglomerate of their own cells, viruses, and bacterial symbiont cells. Indeed, the genes in the symbiont population can vastly outnumber the genes of the host, and yet we know little about the frequency at which these symbiont genes are swapped between coinfecting microbes or co-opted by the animal host. Here, I demonstrate that even in the most restrictive class of symbionts, the obligate intracellular bacteria, there is a surprising amount of genetic flux between coinfections. I discuss three primary findings. First, the most common obligate intracellular bacteria on the planet, Wolbachia pipientis, exemplifies extraordinary rates of bacteriophage transfer that are akin to the levels of genetic flux seen in free-living bacteria. Second, genome sequencing demonstrates that whole bacteriophage genomes can transfer apparently unrestrained between related and unrelated intracellular bacteria that coinfect the same host. Third, a new tool is presenteed that rapidly isolates genomes of microbes in a mixture of genomes from various organisms and environments. I conclude that animals are frequently ecological arenas for gene transfer between intracellular bacteria - thereby providing a means by which new genes and functions can be acquired in symbionts and inherited in their animal hosts.


Hat tip to Rob (@liveinsymbiosis) for recoding the video.

The Golden Goose Award and my chat with Congressman Jim Cooper

"We all want our kids to do well in school. We don't want America to lag behind, so often parents are the ones who are making fun of science and scientists. It should be one of the most honorable professions. It's discovering truth." - Congressman Jim Cooper

Image by Ismael Roldan
http://www.wallstreetjournal.de/article/SB123214833023191881.html

As I sat myself into an exit row seat for the flight from Nashville, I looked at the incoming passengers and saw a familiar face sit across the aisle. It took me a few minutes, but I realized it was Congressman Jim Cooper. Since 2003, Congressman Cooper has represented Tennessee's 5th congressional district (Nashville) in the U.S. House of Representatives. He is a member of the Democratic Party and the Blue Dog Coalition. Service runs though this man's DNA. He is the son of former governor Prentice Cooper and interestingly, he served as a professor at Vanderbilt University's Owen Graduate School of Management.

Cooper has recently gotten public and media attention for proposing rational ideas for an irrational congress:

• No budget, no pay for congress (video)
• Bipartisan meetings on a regular basis (video)
• The Golden Goose Award (more on this below)

He is a gentle warrior that is trying to do good in a broken system that for example, as he said to me today "we cant even pass a highway bill". As we landed, I thanked him for his service and introduced myself. I expressed the broken system of science in America, which he was deeply aware of.

After we talked a bit, Cooper brought up the Golden Goose Award - a brainchild of his and a direct mockery of the idea of the Golden Fleece Award, which was used by the late Senator William Proxmire to target so-called wasteful spending of federally funded research. Years in the making for him, the goal of the Golden Goose Award is to flip the Fleece Award on its head to highlight tax-payer funded research to the public and the good that comes of it. What a simple, yet amazing idea! About ten research projects/people will be awarded (which equates to being named, no monetary value of course) in September. He has bipartisan support, which is a triumph in and of itself in Congress. The organizations supporting the award include: American Association for the Advancement of Science, Association of American Universities, Association of Public and Land-grant Universities, Breakthrough Institute, Progressive Policy Institute, The Science Coalition and the Task Force on American Innovation. Im not sure if the deadline has passed, but you can check by requesting a nomination form by emailing info@goldengooseaward.org.

This idea came from Cooper because he was “offended that politicians were making fun of science for their own gain.” It is perhaps the single most refreshing idea on science that I've heard coming from Congress in the last decade. Hat tip to Cooper. You can follow him on Twitter at @repjimcooper or an e-newsletter.

Finally, a shot out to Twitter - I only knew Jim Cooper's face so well because I follow him on Twitter. Meeting Jim Cooper today and sharing the information about the Golden Goose Award would not have happened without Twitter.  It can change a lot in your world for the better. And thanks to those tweeters who got me hooked. You know who you are.

Wolbachia Video Collection

I'm surprised with the difficulty in collating Wolbachia symbiont videos from youtube. You'd think they would pop up immediately with the species name as the search term, but there's all sorts of junk in there. So, here are all the videos that I could collate, in no particular order, but on diverse topics. There's even a special treat of a Wolbachia video done to Lady Gaga's Bad Romance song. If you know of other Wolbachia videos, please let me know and I'll add them in. If you're feeling adventurous, check out the Wolbachia band video (heavy metal) at the end. Somebody has a sense of humor.

Is the Microbiota Species Specific? Cell paper weighs in.

A just published Cell paper, Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota, weighs in on the growing evidence that the gut microbiota is specific to a host. In this case, the study shows that non-native microbiotas, including human and rat, colonize a mouse gut, but those bacterial species do not work with the resident mouse cells to mount a proper immune response. Simply stated, you can put non-native microbes in an animal, but you dont get a fit animal back.

Highlights from the paper:

• Mouse and human microbiota differ in bacterial species, primarily within Firmicutes
• Human microbiota (HMb) colonized mice have a global immunodeficiency like GF mice
• HMb induced less T cell proliferation and activation than mouse microbiota (MMb)
• HMb mice are more susceptible to enteric and disseminated infection than MMb mic

Video link of the senior author and Harvard professor, Dennis Kasper, describing the paper:

This work contributes to an emerging body of literature that supports the hypothesis that a minor or major part of the assemblage of the OTUs in the microbiota interact with the host in a specific manner. The consequence of this specificity is that assemblages of bacteria in related species may actually change in composition over time in parallel with the phylogeny of the host species. Thus, the bacterial OTUs could be a general extension of the host's genes, and there is an evolutionary footprint in the changes in both. We saw this in Nasonia wasps (Evolution paper here) and have summarized other evidence in Box 1 of this review (Trends in Ecology and Evolution paper here).

All this makes me wonder how important symbiosis will turn out to be in speciation. If the pace of new discoveries is any indication, it is looking like the old ideas of the 80's and 90's (that symbionts do not assist speciation in any grand way) is going to be entirely reassessed.

Related Blog Posts:

• Speciation by symbiosis (April 26, 2012)
• Is the microbiome part of the organism or the environment? (May 11, 2012)

The Universality and Complexity of Viruses: A Brief Story Behind Our New Review

From Bordenstein et al 2006 PLoS Pathogens. Bacteriophage particles are denoted by the arrow heads inside Wolbachia cells that inhabit the testes. Particles are observed to be lysing Wolbachia in the two images on the right, such that DNA is degraded, membranes are detaching from the surface, and particles are exiting the cell.

 100 years ago, we were unaware that viruses even existed. Today, they are recognized as the most abundant biological entity on the planet. Despite their ubiquity, there was an expectation that there would be some form of limit to the distribution of viruses.

In particular, viruses require a host to replicate inside and some host organisms live in such a confined niche that they may be a boundary to the frontier of viruses.

What kinds of hosts are we talking about? Obligate intracellular bacteria or bacteria with reduced genomes that are confined to replication inside host cells. These bacteria comprise some of the most intimate and long-lasting interactions on the planet - Chlamydia, Wolbachia, and the bacterial ancestors of mitochondria and chloroplasts. Are these species unique in that the viral frontier does not reach them? And if it does reach them, do their viruses evolve differently from viruses that live in less constrained niches such as bacteria that replicate in the open environments of land and water.

As it turns out, many obligate intracellular bacteria, especially those that switch hosts, are rampant with mobile genetic elements including viruses.

For a summary of this topic and specific studies on viruses in Wolbachia, my student Jason Metcalf (@JMetcalfVU) and I just published a review in a special issue on viruses in Current Opinion in Microbiology, entitled The complexity of virus systems: the case of endosymbionts. 

Jason is a M.D./Ph.D. student in the The Vanderbilt Medical Scientist Training Program (MSTP). He joined the lab in the summer of 2011 to develop bacteriophage WO into a therapeutic treatment against its host Wolbachia. The phage could offer a naturally-evolved way to kill Wolbachia involved in human diseases.

A few salient points of the review are:

1. Wolbachia pipientis infects a vast number of animal species and often has a significant portion of its genome dedicated to proviral sequences of a virus called WO. 
2. A Wolbachia genome typically has one full temperate virus and several degraded relics of previous WO virus invasions.    
3. WO biology has updated fundamental theories of viral and endosymbiont evolution, namely The Phage Modular Theory and endosymbiont genome stability. 
4. Active WO always transfers between Wolbachia coinfections in the same host. 
5. Despite its rampant mobility, WO exhibits features of genomic constraint related to its intracellular niche, including gene deletions and infrequent acquisition of new genes. 
6. Active and remnant fragments of WO retain an unusual core genome of head and baseplate genes; other genes are frequently deleted. (would love to know why?)
7. Up to 87% of the divergent/absent genes between closely related Wolbachia strains is due to prophage WO

Did you miss Wolbachia 2012? Fear not...

Discover the Microbes Within: The Wolbachia Project on CNN iReport

Colorado High School Students Dissect Insect DNA for Wolbachia (CNN iReport)

One of the most rewarding aspects of being a scientist is seeing its undeniable impacts on students. 

This is a brief mention that CNN iReport posted a panel of 10 high resolution images and a story with some good quotes on a Peyton, CO classroom doing our science education series called Discover the Microbes Within! The Wolbachia Project. 

The Wolbachia Project's website is here.

I consistently hear from students that this discovery-based project is the best lab they do all semester and this high school group is no exception. Kudos to the talented teacher, Paul Austin, and his 25 new microbiologists/Wolbachia fans. 

Notable quotes from the iReport:

“This is exciting,” said Jaren Prestwich, 16, an eleventh grade advanced placement student at Falcon High School. “We’re getting in there and being a part of the whole field of science... This is actually recorded at the national and international levels.”

“These students are doing high-end scientific research,” said science teacher Paul Austin, who brought the project to 25 AP students at the high school

“This project pulls students into real world scientific research that teaches critical thinking and lab skills,” said Austin

“I didn’t know it’d be this complicated... Everything is so precise, so exact,” said Reyes. “I never expected to participate in a nationwide project.”  

 

Is the microbiome part of the organism or part of the environment?

One of the central questions in the science of the microbiome is whether an animal’s genes or diet determine the composition of gut bacteria. This debate gets murky very quickly as it raises the fascinating question of whether you should consider your gut bacteria a part of you, just like the genes on your chromosomes in your gut cells, or a part of the environment that affects you, like a fruit that provides you nutrition on a daily basis or a parasite that occasionally makes you sick.

Approaches to studying gut bacteria in humans have largely been diet-centric, and we are reminded of this pattern by the news coverage this week of a heroic microbiome study by Rob Knight's and Jeff Gordon's labs. For starters, here's one good example published by Science Now - Your Inner Bugs are What You Eat. 

This study measured the number and types of gut bacteria in people from three very different populations - the Venezuelan Amazon, Malawian villages, and three American cities. Similarities and differences in their gut microbes were found but the news spin is that the microbial differences are driven by diet. This extrapolation goes too far, as these populations not only differ by diet, but also in so many other environmental and biological traits.

Diet clearly plays a role in shaping the microbiome. This fact is undeniable. But it is not the sole contributor. Genes are important and the relative importance of genes vs. diet remains a key question of the science of the gut microbiome. Before jumping too quickly into the diet camp, consider this observation.

• We raised insect species on exactly the same diets (download here), yielding a null hypothesis that if diet is the sole player in shaping the gut bacteria, then each species would have the same microbiome. To the contrary, evidence supports the alternative hypothesis that the microbial assemblages were different between the species and in fact the assemblages were related to each other in the same manner that the insects' genes were related to each other. To put it simply, even when diet is controlled for, the species' genes select for variation in the microbiome.

As in most scientific debates, it will likely be the merger of opposing ideas that ultimately fashions the knowledge. Diet and genes shape the microbiome. But whether your gut microbes should be considered part of the environment or part of you is up for continued discourse. What do you think?

Science of a Superorganism - my article in Bare Essentials

Bare Essentials - A Free Online Magazine Promoting Life Science and Conservation:  Bare Essentials is an open access online journal that has a commitment to spreading scientific literacy along with some snazzy designs/layouts in their articles. The editor of Bare Essentials asked for a contribution on the relationships between the microbiota and evolution. The article, entitled Science of a Superorganism, is downloadable here.

BE has progressive principles that deserve giving a shot out to, including an affiliation with the Australian Zoo Wildlife Warriors, a conservationist organization that was established in 2002 by the late Steve Irwin and his wife Terri Irwin to involve and educate others in the protection of injured, threatened or endangered wildlife. From the Bare Essentials website:

"Beyond our online resources and publication, we help co-ordinate fundraising opportunities for our conservation partners inviting individuals, groups and sponsors to affiliate with and help raise awareness for preservation efforts through our Wildlife Warriors Initiative."

Spotlighting the Stories of the Microbiota: There's so much to say about the microbiota that it was impossible to cover all the work that should be covered; and there are many good articles already out there. My approach was to boil down the basics and shine the lights on the importance of the microbiota for the general audience. I included topics such as how microbes weigh over 5000x more than humans do on the planet, how microbes make you attractive to mosquitoes, how women's hands are microbial dirtier than men's hands, among others.

I also tried to pick up some of the things that my student is studying on gut microbiota and evolution. Here are two more scientific points that are touched upon towards the end of the Bare Essentials piece but dont get much real estate in the article:

1. First, the influence of gut bacteria on animal speciation is one of the major foci of our lab's research. We are studying how changes in the number and types of gut bacteria change during the process of animal speciation, and how the gut bacterial community may in fact cause speciation events by reducing interbreeding between two animal species. Recently we published a paper in the journal Evolution in which we showed that gut bacteria in closely related species of insects, Nasonia parasitoid wasps, increases in diversity over development from larvae to pupae and adults. The gut bacteria essentially becomes more diverse by colonization of new bacterial types as the insects develop, similar to what happens within humans in which an infant rapidly accumulates different species of bacteria over the course of their first year. 
2. We also test whether diet or animal genes have a more important impact on the composition of the types and abundance of bacterial species in their guts. If diet affects the gut microbiota, then by rearing closely related species on the same diet, the null hypothesis would be that all three species harbor the same types of bacteria. We did not observe this. Instead, what we observed is that when the Nasonia wasps were reared on the same diet (fleshfly hosts), the bacterial communities became slightly different in each of the wasp species; and the relationships of these slightly different gut communities between the Nasonia species parallels the relationships of the Nasonia chromosomal genes (see conceptual figure below based on findings in the Evolution paper). Therefore, we conclude that bacterial communities diverge in parallel with the wasp's genes over evolutionary time-frames that span the formation of new species. The implications are significant. In particular, a host's bacterial population is not transient or unstable. Instead, it is species-specific at some levels and likely selected for by the immune system to perform functions within the host that may be slightly different from the functions in closely-related host species. What happens to these bacterial communities in hybrids and how the bacteria affect hybrid problems such as mortality between Nasonia species is what we currently have our heads buried in.

The figure above by Robert Brucker and I shows the codivergence between the genes of the wasp on the left and their gut microbial communities on the right. The three Nasonia species differ in their wing sizes and the fleshfly host on the bottom is Sarcophaga bullata. The bolded colors on the circular trees indicate the different types of bacterial species present in the insects.

The Story Behind Our New Review: "Speciation by Symbiosis"

This post is a behind-the-scenes look at our new review, entitled Speciation by Symbiosis, by graduate student Robert Brucker and I. The review is online today in Trends in Ecology and Evolution. If anyone needs a copy, Ill happily send you one. Here are four points that motivated us to write the review.

1. The study of microbial symbionts in speciation has an interesting history: One of the central questions in evolutionary biology remains how do new species arise. What types of genes and evolutionary forces spur one species to split into two, ultimately to form the 1.8 million species on the planet? While we clearly have answers today that shed some light on these questions, debate remains about what types of heritable factors are important in promoting speciation. Specifically, these factors include two possibilities: (i) the genes on an organism's chromosomes versus (ii) the microbial symbionts that inhabit that same organism. The controversy over this topic actually began a century ago among evolutionary biologists and geneticists.  The main demarcation in the debate was best represented by two books, one of which was nearly forgotten to history and is the inspiration for the review, as well as our grant (press release) from the National Science Foundation's Dimensions of Biodiversity Program.

The forgotten book and the famous book that complements it are:

• by microbiologist Ivan Wallin - Symbionticism and the Origin of Species (1927), and 
• by geneticist Theodosius Dobzhansky - Genetics and the Origin of Species (1937)

Given the uncanny similarities in titles and the time frame of their publications, I think it is likely that Dobzhansky "copied"  Wallin's title and replaced Symbionticism (meaning intracellular symbioses with microorganisms) with the word Genetics.

A 1920 photo of Ivan E. Wallin. Wallin was a professor in the Department of Anatomy at the Univ. of Colorado Medical School, Boulder and was most well known for recognizing that mitochondria as bacteria. Credit: Archives, University of Colorado at Boulder Libraries. Colorado, U.o. (1920) Junior Class. In College of Liberal Arts, Univ of Colorado, Boulder.

2. Ivan Wallin's Hypothesis Was Ahead of His Time: Wallin’s central thesis was that the universality of bacterial-derived organelles (i.e., mitochondria) reflected the importance of bacterial symbionts as building blocks of evolutionary change and ultimately new species. Despite Wallin’s effort to put microbial symbiosis into the mainstream of evolutionary biology in the early 1900's, it was Dobzhansky’s work that would have a lasting influence. From the Biological Species Concept to the Dobzhansky-Muller-Bateson model of postzygotic isolation, Dobzhansky et al laid a solid foundation for the study of the genetics of speciation. Experimental and theoretical investigations of symbiont-assisted speciation were far and few between as speciation genetics took off in the 80's and 90's by many science idols of mine.

 

3. Today's biotechnology and thinking are up to the task: With the advent of high throughput sequencing techniques that make the identification of bacterial symbionts simple, and today's recognition of microbial symbiosis as a requirement for complex eukaryotes, Wallin’s ideas on the symbiotic origin of species are primed for a full reassessment. Indeed, the emergence of the bacterial symbiont Wolbachia in topical discussions of speciation (book chapter) was a beginning to reviving Wallin’s silenced ideas. The emerging story supported by the latest science in our review is that biologists have even farther to go with symbiont-assisted speciation. It appears to be almost a given that studies of the general microbial community of animals and plants will reveal even grander ways in which microorganisms act as causative agents of their host's speciation.

  

4. A new phase in the study of symbiont-assited speciation is happening now: Our article begins begins with a rich, historical controversy in evolution and genetics. Where that debate goes in the future is up for scientific discourse and experimentation. Rob Brucker (@liveinsymbiosis) and I suggest in the review that the current evidence for symbiont-induced speciation is far more solid than many speciation geneticists appreciate, and a new phase of speciation by symbiosis is likely to spur many exciting new insights.

We suggest that as studies of microbe-assisted speciation march forward, Ivan Wallin should be recognized for his pioneering and imaginative work on the microbial basis of speciation. Here is arguably his greatest quote:

“It is a rather startling proposal that bacteria, the organisms which are popularly associated with disease, may represent the fundamental causative factor in the origin of species.” (Ivan E. Wallin, 1927)