Friday, October 2, 2015

Wolbachia Milestone: "Video Game" Status

There are many reasons why Wolbachia bacteria are one of the most amazing microorganisms that you'll ever read about (and why scientists have studied them for almost a century now). For starters, they curiously dwell inside the cells of animal gonads (testes and ovaries) spanning insects to filarial worms. Second, they can change the gender or reproduction of those insects. Third, they can not only prevent mosquitoes from passing on dengue virus to humans, but they may also be a target for curing diseases such as lymphatic filariasis or river blindness. Fourth, they are one of the best cases of how infectious microorganisms can assist the origin of new species. 

Among many other astounding facts, Wolbachia have become so famed apparently in the popular news that they are also now featured in the video game series Metal Gear Solid 5. A friend pointed me to this sound track yesterday with the quote "can't escape it - Wolbachia are now making appearances in video games. Wolbachia in this game are used by the enemy to create a pathogen that kills people speaking only certain languages". 

The full video / sound track is here:

The two clips where Wolbachia are featured are:

and here:

Sunday, July 12, 2015

PeerJ has 5 Nobel Prize Winners on Editorial Board

Our lab has largely embraced the open access paradigm in recent years by choosing, when possible, to publish in open accesss journals. For our highest quality work, we typically submit to PLOS Biology  (Mom Knows Best by @DNAdiva87 and Host Biology in Light of the Microbiome with @KevinRTheis) and eLife (Antibacterial Gene Transfer by @JMetcalfVU). For other papers in the last couple of years, we supported PeerJ (our articles here) - a disruptive, open access publisher and award winning biological and medical sciences journal that publishes reviews and rebuttal letters alongside each article, is fully transparent in the review process, and is importantly affordable. Imagine my surprise today then when I searched the editorial board and found FIVE, count them yourself below - FIVE!!, Nobel Prize winners as well as colleagues Jonathan Eisen and Irene Newton. Anyone else blown away? If so, then support PeerJ.

Friday, June 12, 2015

What are Holobionts and Hologenomes?

For the past eight months, Kevin Theis and I have been working hard on an essay on holobionts and their hologenomes. These terms and concepts are well known to a small cadre of biologists, but otherwise are mired in confusion in part because the literature in this area is diffuse and sparse. Our paper has now gone through a mostly transparent review, and in and outside of that process, we have received some excellent feedback from colleagues in the community. Im particularly interested in scaling the feedback up and crowdsourcing the process through the comments section below. Some of these principles may not make sense to the reader because we have not yet put forth the entire manuscript (due to be published this year). Nonetheless, I hope that some of what's below resonates with readers to stir a lively discussion. Thanks in advance for your perusal and feedback if you can. This is a draft in progress that can only improve with your insights. 

I. Holobionts and hologenomes are units of biological organization

o   Complex multicellular eukaryotes are not and have never been autonomous organisms, but rather are biological units organized from numerous microbial symbionts and their genomes
o   Biomolecular associations between host and microbiota are more conceptually similar to an intergenomic, genotype x genotype interaction, than a genotype x environment interaction

II. Holobionts and hologenomes are not organ systems, superorganisms, or metagenomes

o   As holobionts are complex assemblages of organisms consisting of diverse microbial genomes, biology should draw a clear distinction between holobionts/hologenomes and other terms that were not intended to describe host-symbiont associations
o   Organ systems and superorganisms are biological entities comprised of one organism's genome; Metagenome means "after" or "beyond" the genome, does not intrinsically imply organismality for environmental samples, and obviates the obviates the fundamentals of symbiosis in the holobiont

III. The hologenome is a comprehensive gene system

o   The hologenome consists of the nuclear genome, organelles, and microbiome
o   Beneficial, deleterious, and neutral mutations in any of these genomic subunits underlie hologenomic variation

IV. Hologenomic evolution is most easily understood by equating a gene in the nuclear genome to a microbe in the microbiome

o   Evolution for both genes and symbionts is fundamentally a change in population frequency over successive generations, i.e., the fraction of holobionts carrying that particular nuclear allele or microbe.
o   Covariance of hosts and microbes in a holobiont population (i.e., community genetics) follows a theoretical continuum directly to coinheritance of gene combinations within a genome (i.e., population genetics)
o   A grand unified theory of evolutionary and ecological genetics deserves priority attention

V. Hologenomic variation integrates all mechanisms of mutation

o   Every hologenome is a multiple mutant meaning that there is variation across many individual genomes spanning the nucleus, organelles, and members of microbiome
o   Base pair mutation, horizontal gene transfer, recombination, gene loss and duplication, and microbial loss and amplification are all sources of variation

VI. The hologenome concept reboots elements of Lamarckian evolution

o   Although Lamarck never imagined microbes in his theory, applying the tenets to holobionts rebirths some major aspects of Lamarckism
o   The nuclear genome is inherited mainly within a Mendelian framework, but the microbiome is originally acquired from the environment and may become inherited
o   Host-microbe associations can forge disequilibria via parental transfer or stable environmental transmission

VII. The hologenome concept fits squarely into genetics and accommodates multi-level selection theory

o   Multi-level selection theory asserts that selection operates across multiple levels of genetic variation with phenotypic effects, from genes to hologenomes and beyond
o   Holobionts are exclusive to hosts and their associated microbiota. Different holobionts, such as a pollinator and flower, interact with each other under standard ecological principles

VIII. The hologenome is shaped by selection and neutrality

o   Natural selection can work to remove deleterious nuclear mutations or microbes, while spreading advantageous nuclear mutations or microbes. In the absence of selection, the neutral spread of hologenomic variation through populations is an inherently stochastic process
o   Mixed ecological models of stochastic and deterministic community assembly likely reflect natural systems, and partitioning the microbiota into stochastic versus deterministic subunits will be an important future goal of the field

IX. Hologenomic speciation blends genetics and symbiosis

o   The Biological Species Concept was never intended to be exclusive of symbiosis, though history largely divorced the two and created unnecessary controversy
o   Antibiotic or axenic experiments in speciation studies must be a routine, if not obligatory, set of experiments in genetic analyses of speciation for an all-inclusive understanding of the origin of species.

X. Holobionts and their hologenomes do not change the rules of evolutionary biology

o   There is no fundamental rewriting of Darwin's and Wallace's theory of evolutionary biology, though the concepts redefine that which constitutes an individual animal or plant

o   Simply put, if the microbiome is a major, if not dominant, component of the DNA of a holobiont, then microbiome variation can quite naturally lead to new adaptations and speciation just like variation in nuclear genes

Friday, May 29, 2015

Holobionts and Their Hologenomes

The 2015 American Society of Microbiology general meeting kicks off on Sunday in New Orleans (#ASM2015 for Tweeters). The agenda looks incredible (as usual, ASM is one of the best conferences of the year), and I am very excited to announce the Monday 2pm session: "Holobionts and Their Hologenomes". As far as I am aware, it is the first symposium for the topic at a major society meeting. We've got a great gender balance of speakers, including the headliners and pioneers in the area, Eugene and Ilana Rosenberg. We're missing many other pioneers who I wished to include, but alas the session is populated by senior and junior investigators and students - the way ASM likes it and it should be. We should work to have a future meeting solely on the topic. My thanks to all of the speakers and session shepherds Joerg Graf and Ned Ruby for their input along the way. If you're going to ASM, stop by Room 260 on Monday at 2pm. 

I believe this session and scholarship echoes the sentiment expressed by the late Carl Woese when he wrote in 2004: 
"The time has come to replace the purely reductionist eyes down molecular perspective with a new and genuinely holistic, eyes up, view of the living world, one whose primary focus is on evolution, emergence, and biology's innate complexity." 
Though instead of "replace", "unify" works best. 

Convener6/1/2015 2:00:00 PMSeth Bordenstein; Vanderbilt Univ., Nashville, TN 
From the First Eukaryote to Man: The Hologenome Concept6/1/2015 2:00:00 PMEugene I. Rosenberg and I. Zilber-Rosenberg; Tel Aviv Univ., Tel Aviv, Israel
Nerve Cells are Involved in Maintenance of the Hydra Holobiont6/1/2015 2:30:00 PMKatja Schroder; Zoological Inst., Kiel, Germany
A Critical Role of the Plant Microbiome for Immunocompetency6/1/2015 2:45:00 PMJ. M. Kremer1, B. Kvitko1, J. P. Jerome1, J. M. Tiedje1, S. He2;  1Michigan State Univ., East Lansing, MI, 2Howard Hughes Med. Inst., East Lansing, MI
Sponge Hologenomics: Unlocking the Ianthella basta Symbiome6/1/2015 3:00:00 PMNicole Webster; Australian Inst. of Marine Sci., Townsville, Australia
Amphibian-Microbial Symbiosis: Unraveling the Role of Host Species, Habitat, and the Pathogen Batrachochytrium dendrobatidis on Skin Bacterial Community Structure6/1/2015 3:30:00 PME. A. Rebollar Caudillo1, M. Hughey2, D. Medina2, S. Loftus2, L. L. House2, R. N. Harris1, L. K. Belden2;  1James Madison Univ., Harrisonburg, VA, 2Virginia Tech, Blacksburg, VA
Microbe-Cycling in Tree Sloths Facilitated by Pyralid Moths6/1/2015 3:45:00 PMK. A. Dill-McFarland1, J. N. Pauli1, M. Z. Peery1, P. J. Weimer1,2, G. Suen1;  1Univ. of Wisconsin-Madison, Madison, WI, 2USDA Agricultural Res. Service, Madison, WI
It Takes a Village: Community Interactions in the Fungus-Growing Ant Symbiosis6/1/2015 4:00:00 PMJonathan L. Klassen; Univ. of Connecticut, Storrs, CT

Monday, May 18, 2015

Ridding bacteria of antibiotic resistance by gene editing

Really interesting development for research on antibiotic resistance and "phage therapy".... (Source and research article)

Targeting Antibiotic-Resistant Bacteria with CRISPR and Phages

Researchers develop a CRISPR-based, two-phage system that sensitizes resistant bacteria to antibiotics and selectively kills any remaining drug-resistant bugs. 
By  | May 18, 2015
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WIKIMEDIA, DR GRAHAM BEARDSUsing bacteriophages to deliver a specific CRISPR/Cas system into antibiotic-resistant bacteria can sensitize the microbes to the drugs, according to a study published this week (May 18) in PNAS. The approach, developed by Udi Qimron of Tel Aviv University and his colleagues, is a modified version of phage therapy that does not require the delivery of phages to infected tissues and could help offset the pressure on bacterial populations to evolve drug resistance, according to the team.
Unlike classic phage therapy, which uses one or more types of phages to infect and lyse specific bacterial strains, the crux of this new approach is using these specialized viruses to supply CRISPR/Cas to rid bacteria of antibiotic-resistance plasmids in the environment before the microbes are able to infect a host. Each phage is specific to a bacterial species or strain and, using CRISPR, researchers can target a specific bacterial sequence.
“The CRISPR technique is at the heart of [this work],” said Michael Terns, a research professor of biochemistry, molecular biology, genetics, and microbiology at the University of Georgia who was not involved in the work. “It’s a nice application of the CRISPR system to attack resistance genes using phage as a vehicle.”
“The classic phage approach doesn’t distinguish between bacteria that are truly pathogenic versus their very similar neighbors,” said Timothy Lu, a professor of biological and electrical engineering at MIT who was not involved in the work. “The idea of CRISPR-based approaches is to enact sequence-specific antimicrobial activity, placing selective pressure against genes that are bad rather than conserved bacterial targets.”
Qimron and his colleagues first created an E. coli-targeting lambda phage that encodes the CRISPR genes plus spacers that target two conserved β lactamases, enzymes that confer resistance to β-lactam antibiotics. Once integrated into the E. coli genome, the phage prevented the transfer of β lactamase-encoding plasmids and could also delete these plasmids from individual bacterial cells. These lambda phage-encoding bacteria become sensitive to treatment with antibiotics.
The researchers then inserted the same β lactamase-targeting spacer sequences into lytic phages that cause bacterial cell lysis. When the lytic phage enters an E. coli cell encoding the CRISPR-phage, its DNA is cleaved, conferring a survival advantage for the antibiotic-sensitive bacteria. In the presence of the lytic phages, bacteria that don’t receive the CRISPR treatment are killed by the lytic phage. “Adding the lytic phages changes the selective pressure in the environment so that sensitive bacteria are favored over the resistant bacteria,” explained Qimron.
His team was not the first to use this approach. Lu and his colleagues last year showed that they could kill antibiotic-resistant bacteria using phages that transferred an antibiotic-resistance targeting CRISPR/Cas system. Another group showed that the CRISPR/Cas9 system could be used reduce the colonization of skin by virulent Staphylococcus aureus in a mouse model.
Among the potential limitations of this approach, “finding a phage for each pathogenic strain is something that has to be worked out,” Terns told The Scientist.
Qimron’s team will next try to apply this CRISPR/phage system on Pseudomonas aeruginosaone of the world’s most prevalent antibiotic-resistant pathogens that cause hospital-acquired infections—and test whether bacterial sensitization works in a more complex microbial environment—the mouse cage.
While promising, the approach does not address the development of antibiotic resistance. Lu noted that resensitizing drug-resistant bacteria is only a piece of the puzzle. “The way I view it is not that we will be able to make an evolution-proof therapy, but that the genetic engineering tools will become more robust so that as evolution happens, we can rapidly develop countermeasures,” he said. “It will be very hard to make evolution-proof therapy, there is just too much pressure for the bacteria to survive.”
I. Yosef et al., “Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria,” PNAS, doi:10.1073/pnas.1500107112, 2015. 

Thursday, May 14, 2015

Mothers, Infants, and The Microbiome

New study from Sweden on the microbiome in the first year of life shows that:

•Gut microbiomes of 98 mothers and their infants during the first year of life was assessed
•Cessation of breast-feeding drives the maturation of the infant gut microbiome
•Shifts in signature species demonstrate nonrandom transitions in the infants’ gut
•Changes in nutrient and xenobiotic metabolism mark maturation of the gut microbiome

(Source) Like babies themselves, the intestinal microbiomes of infants start out in an immature state and over time grow into communities similar to those of adults. In a new survey of 98 Swedish babies whose microbiota were sampled several times during their first year of life, researchers found that the microbiomes of breastfed infants persisted in a “younger” state longer than those of non-breastfed babies, even after the introduction of solid foods.
The conclusion that “stopping breastfeeding—rather than introducing solids—drives maturation is a new idea, because we all thought so far that solids introduction was a key factor in changing the microbiota,” said Maria Gloria Dominguez-Bello, a microbiologist at New York University School of Medicine who did not participate in the study.
Researchers from University of Gothenburg in Sweden and their colleagues found more adult-like taxa in the microbiomes of babies who stopped breastfeeding earlier, while the microbiota of babies breastfed for longer were dominated by bacteria present in breastmilk. The results, published today (May 13) in Cell Host & Microbe, are part of an effort to catalog the microbial changes that occur as children age and to note how those changes correlate with health and disease. Fredrik Bäckhed of Gothenburg and his colleagues collected stool samples from 98 moms and their newborns, and again sampled the babies’ stool at four and 12 months.
Unlike other studies that identified babies’ gut microbial taxa using 16S sequencing, Bäckhed’s team took advantage of metagenomic shotgun sequencing, which can be used to pick up on previously unknown microbes. “We have identified more than 4,000 new microbial genomes” as part of this project, Bäckhed told The Scientist.
Confirming previous work, his team’s analysis found that the 15 babies born via cesarean section were colonized by different bacteria—many from oral and skin communities—than babies born vaginally, who shared numerous microbes with those present in their mothers’ stool.
Because shotgun sequencing enabled the group to examine genes prevalent in the microbiome, Bäckhed’s team looked at the functionality of the intestinal microbiota as babies transitioned to different foods. For instance, in the vaginally delivered newborns’ microbiomes, genes that break down sugars in breastmilk were common. As these babies celebrated their first birthdays, the genes in their microbiomes favored the ability to breakdown starches, pectins, and more complex sugars.
“What’s nice about this paper is that they show this maturation [of the microbiome] in normal, healthy kids in a Western population follows this transition based on diet,” said Steven Frese, a postdoc at the University of California, Davis, who penned a commentary accompanying the study with his advisor, David Mills. “Being exposed to new foods promotes the growth of new bacteria that can consume them,” Frese told The Scientist.
However, as the authors noted in their study, “the increased capacity to degrade polysaccharides promoted by the introduction of solid foods did not become apparent until the infants stopped breast-feeding.” In other words, continued breastfeeding appeared to tamp down the functional changes in the microbiome that occured as the babies were exposed to new foods.
Bäckhed said the study cannot determine whether any particular microbial profile is better for babies than another. “The healthy microbiome probably covers a wide spectrum,” he said. “We can’t say who is predisposed to disease.”
He is continuing to follow the children as they get older to observe whether alterations in microbial communities are associated with disease. “This is quite an extensive characterization of the microbiome at some critical points during the first year of life that sets a basis for future research.”
F. Bäckhed et al., “Dynamics and stabilization of the human gut microbiome during the first year of life,” Cell Host & Microbe, 17:690–703, 2015.

Wednesday, April 29, 2015

Margaret McFall-Ngai waxing on the Beauty of Small Things


Published on Apr 3, 2015
Recent technological advances have presented a new view of the world to biologists, one in which obligate alliances between animals and microbes are the rule rather than the exception. The microbial partners, while sometimes occurring at such densities as to be visible to the naked eye, are often best studied with the use of powerful microscopes. The combination of the subject matter and the microscopic methods render the images startlingly beautiful.

In a November 2014 lecture at Mann Library, Margaret McFall Ngai reflects on new research that has dramatically changed our understanding of the ways in which microbes are crucial to the well-being of plants and animals, and explores the new ways that both scientists and artists are finding to express the beauty of this symbiotic relationship.

Dr. McFall Ngai is Professor of Medical Microbiology and Immunology at the University of Wisconsin-Madison and affiliate professor at the University of Hawaii. One of the foremost life scientists in the fields of immunology, symbiosis, and marine biology, she is also serving as Andrew Dickson White Professor-at-Large at Cornell University through 2017.

Tuesday, April 28, 2015

My talk at the Early Career Scientists Symposium on The Ecology and Evolution of the Microbiome

The microbiome is arguably one of the hottest areas in biology today. On March 28, 2015, the Department of Ecology and Evolutionary Biology at the University of Michigan recognized the basic sciences of this burgeoning discipline and hosted an exciting international symposium for young scientists about the ecological and evolutionary processes of the microbiome. Several early career scientists who are at the forefront of studying ecosystems within organisms were invited to present their work and to participate in panel discussions. A summary of the event's common themes, advantages for young scientists, and future outlook can be found at the University of Michigan's Program in Biology site. The early career presenters were Drs. Katherine Amato, Justine Garcia, Andrea Jani, Kevin Kohl, Angela Poole, Rachel Vannette, Kelly Weinersmith. The keynote speakers were Georgianna May and myself. I really enjoyed talking with everyone, and it appears that Georgianna and I may embark on a publication together as a result of this meeting. Meeting host Kevin Theis and I are also writing a paper entitled Host Biology in Light of the Microbiome: Ten Principles of the Hologenome. More to come.  

I lost my voice the day before this seminar, so raspy and all....I talk about Charles Darwin, Ivan Wallin, The Modern Synthesis, and how the microbiome fits seamlessly into the origin of species. 

Monday, March 23, 2015

My Podcast With People Behind the Science

Just a quick post. I really appreciated the opportunity to record a podcast with People Behind the Science in January; it just posted today. You can read part of the transcript below or listen hereThis podcast series by Dr. Marie McNeely is a wonderful service to science and education as it helps break down the wall of silence between scientists and non-scientists with stories of wit, inspiration, dilemma, light bulb moments and motivation. 

235: Dr. Seth Bordenstein: Seeing Science and Symbiosis Through the Lens of an Evolutionary Microbiologist

Listen to the Episode Here
Dr. Seth Bordenstein is an Associate Professor in the Department of Biological Sciences and in the Department of Pathology, Microbiology, and Immunology at Vanderbilt University. He received his undergraduate, Master’s and PhD degrees from the University of Rochester, receiving his PhD in Evolutionary Genetics. Seth then served as a Postdoctoral Fellow of the National Research Council in the Marine Biological Laboratory in Woods Hole. He worked as an Assistant Research Scientist and Assistant Scientist there and also served as an Adjunct Assistant Professor at Brown University before joining the faculty at Vanderbilt. Among his many honors and awards, Seth has received the Chancellor’s Award for Research and awards for Excellence in research as well as Teaching and Mentoring from Vanderbilt. His research was also featured in as a top story of 2013 in Science News. Seth is here with us today to tell us all about his journey through life and science.
People Behind the Science Podcast Show Notes
Life Outside of Science
When not doing science, Seth spends most of his time with his family. His wife works with him in the lab at Vanderbilt and he has two wonderful daughters.
The Scientific Side
Scientifically, Seth is answering evolutionary biology questions focusing on how one species splits into two, how we achieve the great biodiversity of the planet, and the underlying mechanisms that produce biodiversity.
A Dose of Motivation
“Don’t be trapped by dogma – which is living with the results of other people’s thinking. Don’t let the noise of other’s opinions drown out your own inner voice. And most important, have the courage to follow your heart and intuition.” by Steve Jobs.
“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.” by Ivan E. Wallin
What Got You Hooked on Science?
In college, Seth was struggling to figure out what he wanted to do for a career. However, during his sophomore year, one course in evolutionary biology basically turned him into an evolutionary biologist overnight. This course was taught by two prominent evolutionary biologists Howard Ochman and Allen Orr, and he was immediately fascinated by the field.
The Low Points: Failures and Challenges
Seth’s entire career was on the line when he was nearing the end of his contract at the Marine Biological Laboratory. He was applying for grants with very frustrating results and was beginning to seriously consider alternative career options. Among the options on the table was a career playing poker professionally. Believe it or not, his odds at winning poker were actually higher than the odds for getting a major grant.
A Shining Success!
One science success that Seth has been really excited about examined the role of the gut microbiome in the origin of species. He worked with a talented student to discover that more closely related species have more closely related microbiomes and hybrids can have different microbiomes than either parent. These discoveries were true eureka moments for him and solidified the idea that the pairing of the genome and the microbiome tells a story of ancestry.
Book Recommendations
Symbionticism and the Origin of Species by Ivan Wallin
Most Treasured Travel
In 2009, Seth was able to travel to Japan for an invited lecture. This trip was particularly memorable because Japan was unlike any of the other places he had ever been. He was impressed with the culture, the beauty of the country, and the food. These all left a lasting impact on him.
Quirky Traditions and Funny Memories
As an undergraduate, Seth contributed to some character-building fly room duties that involved cultivating maggots using raw liver. This task was associated with rather unfortunate odors and had to be done even on the weekends. One weekend when Seth went in, the water in the building had been turned off for maintenance, so when he went to clean up and wash dishes afterwards, no water came out. He didn’t learn until later that he had left the sink on with the drain blocked and when the water came back on, the fly room was flooded. This resulted in a big mess including mildew and fungal growth that other lab members had to clean up.
Advice For Us All
Do what you love. This was the single best thing Seth has ever done.
Guest Bio
Seth has broad interests in the role of microbes in animal evolution and health. His lab asks non-linear questions to probe the rules of symbiosis, evolution, and their inseparable connections. They are conducting research to try to uncover the role of the microbiome in the origin of species. Other projects in the lab focus on how viruses subsist in obligate intracellular bacteria. In addition, Seth’s lab is trying to better understand how universal the process of maternal microbial transmission really is. You can learn more about Seth and his research by viewing his lab websitefollowing him on Twitter, or visiting his blog.