BEACON Researchers at Work: Combining Evolution and Engineering in Aquatic Robots

Posted on July 13, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by MSU Visiting Scholar René Draschwandtner.

René after a BEACON seminar

René after a BEACON seminar

Guten Tag, god dag, and good day to all readers. I am René Draschwandtner, a visiting scholar from Salzburg, Austria, although I came to Michigan State University and BEACON by way of Stockholm, Sweden. More on that circuitous route shortly. Since March I have been investigating the behavior of snake-like aquatic robots in Prof. Philip McKinley’s research group. My research involves integrating behaviors observed in animals with the search capability of evolutionary algorithms, enabling robots to conduct complex tasks efficiently.

Genetic Programming output with HeuristicLab.

Genetic Programming output with HeuristicLab.

The first time I encountered evolutionary computation (EC) was at the University of Applied Sciences Upper Austria (UASUA), where I earned a master’s degree in Biomedical Informatics. Ever since I attended a lecture on EC, I have been excited about applying mechanisms from natural evolution to computer algorithms. Especially intriguing to me is exploiting the search capabilities of genetic algorithms for parameter optimization. While at UASUA, I conducted a course project, supervised by Prof. Michael Affenzeller and Prof. Stephan Winkler, where we examined human blood data with evolutionary algorithms in order to find so called Virtual Tumor Markers [1]. We used HeuristicLab, a user-friendly open source tool developed by the Heuristic and Evolutionary Algorithms Laboratory (HEAL), to conduct evolutionary experiments with different parameter settings. Specifically, we explored the effect of different evolutionary parameters on producing Tumor Marker estimation models.

René enjoying the midday sun on a frozen lake above the Arctic Circle.

René enjoying the midday sun on a frozen lake above the Arctic Circle.

After graduation, I immediately enrolled for a second master’s program at UASUA, this time in Information Engineering and Management. I was particularly interested in how the natural sciences, including topics such as evolution, can inform business computation. Especially, the usage of machine learning methods in conjunction with data warehouses in order to generate and predict key figures was one of my favorite topics during my studies. A student exchange program with Stockholm University took me to Sweden in fall 2014. There, I focused on data mining and IT management. The focus on business-IT alignment and IT strategy broadened my mindset beyond my academic knowledge. By the way, if you ever visit Sweden, I highly recommend crossing the Arctic Circle! The frigid and untamed environment is breathtaking.

As I finished my studies in the business domain, I continued to be interested in evolutionary computing in other areas. This led me to another exciting area of study, evolutionary robotics, where evolutionary algorithms are used to produce behaviors, and even bodies, of robots. I wrote a proposal on evolving aquatic robots and submitted it to the Austrian Marshall Plan Foundation. Luckily, the proposal was funded, enabling me to come to Michigan State University and the BEACON Center to complete my final thesis. In addition to Prof. McKinley, I am collaborating closely with Anthony Clark and Jared Moore, who have applied evolutionary computation to several aspects of aquatic robots. Particularly, their work has explored the evolution of behavior in computer simulations [2] and optimization of flexible caudal fins for robotic fish [3].

Robot with evolved gaits transporting payload to a destination region. A video can be seen at https://youtu.be/xWSVBTm4m3c.

Robot with evolved gaits transporting payload to a destination region. A video can be seen at https://youtu.be/xWSVBTm4m3c.

My research project investigates the locomotion behavior of a snake-like robot consisting of several rigid links, in an aquatic environment. The project is based on the idea of creating complex behavior by composing several simple motions, namely the actuation of joints. The task for the simulated robot is to capture and transport a payload to a target. This behavior is useful in the real world such as rescuing an arbitrary shaped object floating in the water. For example, a rescue team on a boat could launch the robot, which would then swim to the object, grasp it, and deliver it to a destination area. Further, the robot would perform these subtasks by simply deforming its body in different ways, without the need for an external propeller or a specialized grasping apparatus.

A key aspect of my approach is to engineer certain behaviors, drawing on the literature, but use evolutionary computation to refine individual behaviors and combine primitive behaviors to form more complex ones. In nature, snake-like animals propagate sinusoidal waves through their bodies in order to generate forward velocity. This behavior is relatively easy to code manually, but we apply evolution to tune parameters so as to maximize performance. Similarly, we can encode a behavior for the snake to grasp an object, but use evolution to determine the precise timing of the grasping maneuver as the robot approaches the object.

My five-month visit to MSU and BEACON will end in late July, after which I will graduate from UASUA. Not only will I be happy to have finished my studies, but I will be able to look back on extraordinary times in Sweden and Michigan.

[1] Winkler, S. M., Affenzeller, M., Kronberger, G. K., Kommenda M., Wagner S., Jacak W., and Stekel H. (2013). On the Identification of Virtual Tumor Markers and Tumor Diagnosis Predictors Using Evolutionary Algorithms. Advanced Methods and Applications in Computational Intelligence, Topics in Intelligent Engineering and Informatics, Vol. 6, 95-122.

[2] Moore, J. M., Clark, A. J., and McKinley, P. K. (2013). Evolution of station keeping as a response to flows in an aquatic robot. Proceedings of the 15th annual conference on Genetic and evolutionary computation:  239-246.

[3] Clark, A. J., Moore, J. M., Wang, J., Tan, X., and McKinley, P. K. (2012). Evolutionary design and experimental validation of a flexible caudal fin for robotic fish. Proceedings of the Thirteenth International Conference on the Synthesis and Simulation of Living Systems: 325-332.

For more information about René’s work, you can contact him at rdraschwandtner at hotmail dot com.

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BEACON Researchers at Work: The Age of Phage

Posted on June 29, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by MSU faculty member Kristin Parent, with John Dover. 

Kristin Parent (center), Natalia Porcek and Jason Schrad at the PVA meeting in Switzerland.

Jason Schrad, Kristin Parent, and Natalia Porcek at the PVA meeting in Switzerland.

This year marks the 100th anniversary of the discovery of viruses that infect bacteria—the bacteriophages. One may think (as many do) that there is little else to gain by continuing to study bacteriophages (often shortened to just phages), but like their bacterial hosts, there is actually still a lot to learn. In fact, I recently attended a Phage and Virus Assembly (PVA) meeting, and the same theme kept coming up: despite 100 years of research, there is still so much that we don’t know.

It might be surprising to learn that the number of phages (~1031) is ten times greater than the number of bacteria (~1030). In fact, one handful of water from lake Michigan contains more phages than there are people on Earth. Think about that the next time you go swimming!

Frederick Twort, in 1915, discovered that bacteria were susceptible to phages, along with Felix d’Herelle’s independent discovery two years later. The next few decades proved to be a robust period for phage research, with an avalanche of studies culminating in >62,700 published papers (as of June 23rd 2015).

  • The 1920s saw the birth of “phage therapy”, in which phages are used to combat bacterial disease.
  • In the 1930s, the phage life cycle was established and is now an introductory biology textbook staple.
  • The 1940s and 1950s saw the use of phages in the famous Hershey/Chase experiment that conclusively showed that DNA is the genetic material, and phages were used in the explosion of molecular genetics studies that followed. In actuality, phages were used as tools that directly contributed to the vast majority of genetic manipulations that are now routine in the laboratory.
  • Phage work continued strong into the 1960s and 1970s where phages again led the way in the creation of methods that are commonplace in the modern laboratory: negative staining in electron microscopy, the use of transposable elements, and DNA sequencing, wherein the first complete genome sequenced by the eponymous Sanger was a phage genome.
  • Research in the 1980s and 1990s revealed that phages were everywhere—in all terrestrial and aquatic biomes.
  • The metagenomics boom starting in the early 2000s gave clues to phages in the human microbiome, and they are now actively being investigated as part of the virome of the microbiome. There are more bacterial cells and phages in your body than there are human cells, and phage/host interactions contribute an enormous amount to our bacterial diversity, and yet, we know so little about them and how they evolve.
  • In the last ten years, advances in cryo-electron microscopy have given us images of the beautiful structures of entire phage particles, which are complexes of thousands and thousands of proteins. We are only now starting to understand how these elegantly assembled structures work as molecular machines.

Despite the huge mass of information gained during the past “phage century”, there are still numerous aspects of phage biology that remain a mystery. One part of this mystery is how a phage, or any virus, recognizes and successfully infects its “favorite” host. Such a process is critical to virus survival. In all environments there is great diversity in both viruses and hosts resulting in an enormous challenge for viruses to encounter and infect suitable targets. My laboratory is focused on how phages efficiently recognize their hosts and transfer their genomes into those hosts. We use a combination of microbiology, biochemistry, structural biology, and experimental evolution to investigate these processes.

One of the phages that we use as a model system is Sf6, which infects Shigella flexneri. Natalia Porcek, a graduate student in my lab, has shown that Sf6 uses a host cell outer membrane protein, or “Omp”, for infection. Her work has shed light on protein-protein interactions critical to Sf6 entry into its host, and her work has contributed to an understanding of host range—specifically, how Sf6 can recognize Shigella and Salmonella species but not E. coli. Another graduate student in my lab, Jason Schrad, is also working toward understanding this process by using cryo-electron microscopy to look at Sf6 during the process of infection.

John Dover counting plaques in the lab.

John Dover counting plaques in the lab.

John Dover, a technician in my lab, and Alita Burmeister, a collaborating student from the Lenski lab, are using Sf6 for experimental evolution studies aimed at understanding how phages can adapt to infect different hosts. These studies have revealed a potentially novel evolutionary mechanism distinct from other phages such as lambda. Sf6 is a member of a class of phages that packages “headfuls of DNA” in its capsid, a protein shell that encloses the DNA. This means that the phage packages DNA until no more can fit in the capsid container, which is more DNA than needed to encode a single genome. We have seen parallel evolution across ten phage lineages that show whole gene deletions as a path to fitness. In some cases, as much as 15% of the ancestral genome was deleted. Since the phage packages headful, that would mean that a new genomic composition (replacing 15% of the DNA), is contributing in some way to a faster life cycle. Their work has also found parallel evolution of cell lysis timing, which is the temporarily controlled stage of the phage life cycle that breaks open the bacteria and releases new phage “babies”. Faster lysis allows the phages to infect the next group of cells in its controlled environment earlier, making the phage more fit.

We still have much more to do to fully understand bacteriophages. We are in an exciting time as experimental advances have evolved to provide many robust tools for dissecting phage biology, and we are looking forward to the next 100 years of phage discovery.

For more information about work in the Parent lab, you can contact Kristin at kparent at msu dot edu.

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BEACON Researchers at Work: An Adventure in Thailand

Posted on June 24, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by MSU postdoc Eben Gering.

I. The Land of the Leech

Figure 1. Golden Naga in Emerald Buddha temple Wat Pra Kaeo, Bangkok, Thailand

Figure 1. Golden Naga in Emerald Buddha temple Wat Pra Kaeo, Bangkok, Thailand

This spring I received a last-minute invitation to join a French film crew in Thailand, which left me a) totally stoked! b) with virtually no prep time. And so I found myself arriving in Khao Yai National Park with a mess of hastily borrowed equipment, abundant enthusiasm, and very little basic information about the region.

For example: did you know that Southeast Asian forests are home to a 150 million-year-old, ten-eyed beast whose name means blood thirsting guts? If you don’t perhaps you are picturing something along the lines of the fantastical Naga (Figure 1) – a ferocious serpent believed to protect the Buddha. Naga guard temple entrances throughout Thailand, but are nowhere near as ubiquitous as Haemodipsidae (Figure 2) which, FYI, are hermaphroditic land leeches.

Figure 2. Haemodipsidae zylandica. One of ~90 species of terrestrial (“land”) leeches.

Figure 2. One of ~90 species of terrestrial (“land”) leeches.

When our guide first offered us prophylactic “leech sox” I didn’t want them. In my undergraduate days I had read a terrific book1 about tropical biology which eventually helped land me in this Thai jungle many years later. One of the book’s most memorable chapters (recapped in a recent radiolab episode) concerns an evolutionary biologist who lets a parasitic botfly pupate in his head for heuristic (learning) purposes. Botfly husbandry has since become a fashionable act among a small and hardcore subset of tropical biologists.

The idea of joining Club Botfly makes me a little queasy, and involves an apparently painful initiation too. But leeches – painless, virtually incapable of transmitting disease, a boon to human health and medicine for at least three millennia – provided an attractive alternative source of field “cred.” In fact, I’ve been quite curious about these animals since meeting Mark Siddall, a passionate and persuasive expert on leech biology who “fishes” for his study subjects by dangling his legs in murky water. In parallel manner, Dr. Siddall advocates for these greatly maligned creatures. He lures his listeners past the ‘ick’ reflex into a reluctant appreciation for their elegance and mystery. It is, after all, an animal which once fed on dinosaurs, and outlived them, and will probably outlast us.

An enlightened view of the leech is also apparent in Khao Yai’s local, Buddhist residents, who point out their relative harmlessness with the saying:

The hero of Khao Yai National Park…

Leeches…

They eat blood but not the trees! 2

Will I be able to get a leech if I don’t wear the sox? I asked Tony, our guide. But I needn’t have worried. In the coming days I would have many chances to observe sanguivory (bloodfeeding) first hand. Leeches would be so abundant at times that we would see and hear them moving towards us on the forest floor.

II. Why won’t the chickens cross the road?

Figure 3. Red Junglefowl (Gallus gallus) eating ectoparasites from a sambar deer (Rusa unicolor). Photo courtesy of Tontantravel.

Figure 3. Red Junglefowl (Gallus gallus) eating ectoparasites from a sambar deer (Rusa unicolor). Photo courtesy of Tontantravel.

The chief purpose of our expedition was to visit the Red Junglefowl (Gallus gallus) within its native range. These extremely wild and elusive birds (figure 3) are the domestic chickens’ closest relatives. The French guys (Figure 4) were out to gather the world’s first 4k footage of wild Red Junglefowl. I, in turn, hoped to gather audio recordings and compare vocalizations to those from a non-native (Hawaiian) G. gallus population. Our recent research3 indicated that Pacific island G. gallus share both Red Junglefowl and “chicken” (i.e. domestic) ancestry. We are now investigating which wild, domestic, and/or hybrid traits have been favored in these feralized populations.

Figure 4. Wildlife filmmakers Benoit Demarle and Nicolas Cailleret

Figure 4. Wildlife filmmakers Benoit Demarle and Nicolas Cailleret

During our first days out, we occasionally heard Red Junglefowls calling from deep within the forest. That’s a somewhat surreal experience for western eyes and ears, because they look and sound just like backyard roosters, yet glide through primary tropical forests without effort, thriving among leopard cats and pythons.

From day one, I was able to collect audio recordings, but our efforts to film (with a menagerie of cumbersome gear) typically sent our targets fleeing dozens, or even hundreds of meters into impenetrable growth. A day’s work yielded only a few precious minutes of 4k video.

On day two, the production director (Benoit) put his cameraman (Nicolas Cailleret, a professional falconer back in France) in a camouflaged bird blind. We left him there before sunrise in an area where we’d seen junglefowl eating figs. Later a hornbill polished off the figs, so we decided to bait the area with another of the Red Junglefowl’s preferred food sources: elephant dung (figure 5).

5a

Figure 5a,b. Elephant dung collected in an attempt to lure Red Junglefowl into the open

Figure 5a,b. Elephant dung collected in an attempt to lure Red Junglefowl into the open

As I grabbed my first handfuls of the dung, which was surprising lofty, fibrous, and not the least bit stinky, I thought how much I love my job. I was 11 time zones from home, and almost intoxicated by the nearly deafening whirs of the cicadas, the sweet and mournful ‘bwoooooops’ of gibbons, the bright flapping of birdwing butterflies gliding on hot, humid air.

While we picked the freshest dung we could find, the waste of our planet’s largest herbivore was already becoming a complex ecosystem. By coincidence, the book I mentioned earlier 1 (and highly recommend) a

lso contained a whole chapter on poop – specifically, how scatophagic4 organisms colonize and compete for this rich resource within minutes of its “birth.”

III. In praise of Bill Nye

Figure 6. Stealth camerawork by Nicolas Cailleret

Figure 6. Stealth camerawork by Nicolas Cailleret

While our brief experiment with elephant dung brought on an existential rapture, it did not bring any Junglefowl in front of the camera. Soon, however, Benoit and Nicolas found other ways to catch clips of the birds in stealth (figure 6). They crouched underneath a camouflage tarp in the bed of Tony’s rolling truck, ready to start shooting when Junglefowl were spotted. They learned and patrolled a few territories’ boundaries. And then, when they had acquired sufficient footage of their non-human prey, they turned the camera on me.

I am curious to see myself on French television, but not worried a bit. I cannot possibly look worse than I felt. For two days I had been crowing for the camera, a one-eyed monster that emitted so much heat it required its own water breaks. Usually this work was done standing in direct sunlight, sometimes while peeling off leeches… whose novelty was waning (sorry, Mark!). The heat seemed to fog up my brain, making it a struggle to follow simple instructions or speak intelligibly. And I could see that this was beginning to try the (extraordinary) patience of the crew – two men who had just spent uncomplaining days in a sauna-like blind surrounded by elephant poop.

On our last afternoon, we all spent an hour crouched in that small, poorly vented vinyl blind collecting footage of me photographing imaginary junglefowl. Nicolas held the camera a few inches from my face while Benoit held the microphone over my head. We were as close together as the heads of the Naga (Figure 1), and it was so hot in there – so very hot and humid (and the whole shot seemed so unimportant) that I wondered if perhaps they were trying to kill me in order to increase their film’s marketability.

But apart from such moments of heat and performance-induced panic, it was a joy to watch Benoit and Nicolas work. There was boldness and creativity in every step of their process, from handling equipment failure, to avoiding extortion by corrupt officials, to framing a narrative arc across this wild landscape, its diverse wildlife, and their bumbling biologist that would eventually reach into the homes of French families.

I was eager to participate in Benoit and Nicolas’ film because nature documentaries helped cultivate my interest in biology. And as a scientist on the more right-brained end of the spectrum, I enjoy seeing artists at work. While I would jump at another such chance, our filming of just one segment (25%) of a 45 minute show was both physically and mentally exhausting. I couldn’t do this work everyday, and have redoubled my respect for the stamina of David Attenboroughs and Bill Nyes.

When I first read Tropical Nature1, my game plan was to become a writer for a documentary production company. But I have since become increasingly fascinated with basic research questions, which take sustained (and sometimes boring) effort to answer. Benoit, on the other hand, began his career as an acarologist (mite expert) before transitioning out of research and into film. The mite work, he said, was much too specialized to match his interests. I could understand this, I said, but also asked him to tell me more about the mites. I think we have chosen wisely.

1 Forsyth, A., & Miyata, K. (2011). Tropical Nature: Life and Death in the Rain Forests of Central and South America. Simon and Schuster.

2 Translation by Elizabeth Borda

3 Gering, E., Johnsson, M., Willis, P., Getty, T., & Wright, D. (2015). Mixed ancestry and admixture in Kauai’s feral chickens: invasion of domestic genes into ancient Red Junglefowl reservoirs. Molecular ecology.

4scat feeding

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BEACON Researchers at Work: The Social Lives of Bacteria

Posted on June 15, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by MSU faculty member Chris Waters.

“Nature red in tooth and claw”-Lord Alfred Tennyson

Tennyson’s famous phrase eloquently describes the adversarial nature (pun intended) that arises from Darwin’s concepts of natural selection and survival of the fittest. From a human perspective, these concepts are easy to understand. One only needs to attend my son’s little league games to see how competition is ingrained in humans. Competition for limited resources leads to genetic winners and losers. This idea permeates throughout the tree of life; indeed, visit the Lenski lab at Michigan State to see the ongoing results of a 25 year Escherichia coli “cage match”.

But we all know that natural interactions are not always adversarial. Humans are also highly cooperative individuals, often helping one another at their own expense. Bees, wasps, and ants, live in highly cooperative communities in which individual members forgo their own reproduction for the net good of the group.

Bioluminescent Vibrio harveyi actively quorum sensing.

Bioluminescent Vibrio harveyi actively quorum sensing.

It has become abundantly clear that even unicellular lifeforms participate in highly complex social interactions. The first appreciation for social interactions in bacteria came with the discovery of chemical communication in bioluminescent Vibrios. It was found that these ocean growing bacteria prematurely induced bioluminescence when exposed to cell-free supernatant harvested from a dense culture. It was subsequently determined that bacteria produce and secrete small chemical signals, termed autoinducers, to coordinate behaviors in response to cell density. We now appreciate that this process, known as quorum sensing, is widespread in bacteria and it is generally hypothesized that all bacteria engage in some form of chemical communication. Autoinducers, and their sensing apparatuses, come in many flavors, suggesting that this is a highly beneficial trait that has coevolved multiple times.

Quorum sensing is often considered to be a mechanism for coordinating cooperative behavior in bacteria. While I think this aspect of quorum sensing is often overstated, it is quite true that many cooperative tasks are controlled by quorum sensing. For example, secreted “public goods” (i.e. shared benefits that all of the members of the community can utilize, not just the producers) are often clearly induced by quorum sensing. This cooperative situation leads to a strong selection for freeloading cheats which can gain the benefit of the public good without paying the production cost. Imagine five students working on a group project-at least one is typically a freeloader who gets the benefit of the grade without putting in the effort. This is an evolutionary smart strategy for the freeloading individual, but this strategy destabilizes cooperation within the group.

Eric Bruger pondering the evolutionary underpinnings of quorum sensing in bacteria.

Eric Bruger pondering the evolutionary underpinnings of quorum sensing in bacteria.

Eric Bruger, a graduate student in my laboratory, is studying this fundamental social evolution question-the evolution of cooperation-in the bioluminescent bacterium Vibrio harveyi. Studying social evolution using bacteria has a multitude of benefits including fast generation times, huge population sizes, easily measurable phenotypes, exquisite control of the environment, and, perhaps most importantly, the ability to genetically manipulate the cooperative state of test subjects (the ethics of genetic manipulation are much less stringent with microbes!).

Eric has found that quorum sensing in V. harveyi does indeed induce public good production, and he has identified environments where public good production is required for growth. When Eric genetically manipulated V. harveyi to unlink public good production from quorum sensing control, leading to constitutive public good secretion, he found that this mutant strain was rapidly invaded by cheating cells. This led to a population crash, typically referred to as a “tragedy of the commons”. However, having the public good linked to quorum sensing stabilized cooperation and the cheats could not invade. Thus, Eric experimentally demonstrated that the ability of cooperating cells to communicate stabilizes cooperation!

Eric then extended these experiments to study the natural emergence of cheats following experimental evolution of V. harveyi for over 2,000 generations. He observed that quorum sensing control of cooperation delayed cheater invasion, but eventually cheaters did emerge. However, communication prevented cheaters from sweeping the population, leading to a complex mixture of cooperators and cheats that is reminiscent of V. harveyi strains observed in the natural world.

Will Soto and Chris Waters glean wisdom from all sources including Bob Marley and Star Wars to study quorum sensing.

Will Soto and Chris Waters glean wisdom from all sources including Bob Marley and Star Wars to study quorum sensing.

Public good production is but one of hundreds of traits regulated by quorum sensing in V. harveyi. How do the other regulated behaviors impact the stability of quorum sensing? Enter Dr. Will Soto, a BEACON funded postdoctoral fellow in my laboratory. Will is exploring the impact of quorum sensing on central metabolism in V. harveyi. Will examined the growth of three strains-the wild type strain with functional quorum sensing, a strain that cannot communicate, and the constitutive quorum sensing strain-in a hundred different laboratory growth media. He found dramatically different growth patterns of these strains, but, surprisingly, the wild type quorum sensing strain did as well or better than both quorum sensing mutants in virtually all environments examined! This result shows that communication in bacteria not only stabilizes cooperation, but it is also a mechanism to enhance colonization of many different ecological niches, suggesting that quorum sensing provides bacteria a large fitness benefit in the real world when faced with ever changing environments.

Quorum sensing is but one of many social traits in bacteria. Most bacteria can also form multicellular communities encased in a protective matrix called biofilms. Some photosynthetic cyanobacteria actually grow as multicellular filaments and exhibit striking differentiation and division of labor. Yet others, like Myxococcus, undergo complex cooperative development and form multicellular fruiting bodies upon starvation. All of these systems are excellent unicellular models to test concepts of social evolution.

Clearly, cooperation is not limited to us multicellular organisms; unicellular organisms have a robust social life. It is important therefore to consider not just nature’s “tooth and claw” but perhaps also “Nature gentle with helping hand”.

To learn more about research in the Waters lab follow us on twitter (@WatersLabMSU) or visit our website: https://www.msu.edu/~watersc3/.

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3rd Annual Big Data in Biology Symposium at UT Austin

Posted on June 9, 2015 by Danielle Whittaker

Summary by UT Austin graduate student and symposium organizer Rayna Harris.

logo

The 3rd Annual Big Data in Biology Symposium on May 15, 2015 was hosted by the Center for Computational Biology at UT Austin and organized by some BEACON members. This annual symposium provided an ideal opportunity to interact with attendees from UT Austin and nearby institutions with an interest in computational biology, bioinformatics, and systems biology. Here, I summarize scientific content of the talks, breakout sessions, poster session, and industry dinner.

The Talks

The symposium talks covered research into epigenetics, genomics, transcriptomics, and immune repertoires in a wide range of organisms. We heard from graduate students, postdocs, and faculty members, providing a diversity of experience and perspective of the impact of big data on biology.

This year’s keynote lecture was delivered by Dr. Shelley Berger from The University of Pennsylvania. She discussed her research into the epigenetic mechanisms regulating of caste-specific phenotypes in eusocial ants. Amelia Hall, a graduate student in the Iyer lab, also focused on epigenetics, describing her analyses of histone pattering in glioblastoma tumors and the effects on gene expression.

BEACONite Dr. Jeffrey Barrick talked about technological advances for mapping beneficial mutations in the E. coli Long-term Experimental Evolution Experiment and the exciting implications for evolution and adaptation. Dr. Kasie Raymann, a postdoc in the Moran lab, talked about her thesis research using large scale genomic data to understand the evolutionary origins of eukaryotes.

Justine Murray, graduate student in the Whiteley lab, discussed her use of RNA-seq and Transposon (Tn) Seq to understand the dynamics of poly-bacterial infections. Dr. Mikhail Matz talked about recent computational tools his lab has developed for analyzing RNA-seq data. BEACONite Dr. Becca Young (Hofmann lab) also described new computational tools that can be used for identifying homologous genes groups, an important step for comparative transcriptomics. Jeff Hussmann, a graduate student in the Press and Sawyer labs, discussed how systematic biases in ribosome profiling experiments can lead to an incorrect understanding of translation speed.

Dr. Jenny Jiang talked about using high-throughput sequencing and single cell analysis to characterize immune repertoires, and Dr. Oana Lungu, a postdoc in the Georgiou and Ellington labs, shared her in silico approach for characterizing changes in protein structure of immune after antigen experience.

The Lunch Breakout Sessions

The lunch breakout sessions provided attendees the opportunity to have small-group discussions with various big data professionals over a catered lunch. These sessions were aimed at helping attendees network with other like-minded researchers and discover resources for different aspects of and opportunities in data science. The three breakout session topics included 1) Big Data in Medicine & Health, which highlighted the tremendous opportunities and technical challenges for evidence-based medicine arising from electronic health records; 2) Careers in Biotech/Industry, which provided insights into non-academic careers; and 3) Open Science, which discussed the importance of data sharing, public access to research, and the increasing role of social media in scientific communication.

The Poster Session

A poster session followed the symposium and allowed trainees to explain their work and facilitate fruitful exchanges. There were twenty posters on various topics, including genomics, transcriptomics, epigenetics, and proteomics. BEACONite Dr. Daniel Deatherage (Barrick lab) and Claire McWhite (Marcotte lab), respectively, won the best postdoc and student poster awards.

Figure 2. The Poster Session. Left: The poster session took place in a lovely ballroom. Right: The symposium ended with a postdoc and graduate student poster award presentation. L-R: Dr. Scott Hunicke-Smith, BEACONite Dr. Daniel Deatherage (postdoc winner), BEACONite Dr. Hans Hofmann, Claire McWhite (grad student winner), and BEACONite Rayna Harris.

The Poster Session. Left: The poster session took place in a lovely ballroom. Right: The symposium ended with a postdoc and graduate student poster award presentation. L-R: Dr. Scott Hunicke-Smith, BEACONite Dr. Daniel Deatherage (postdoc winner), BEACONite Dr. Hans Hofmann, Claire McWhite (grad student winner), and BEACONite Rayna Harris.

The Industry Partners Dinner

This year, we hosted an Industry Partners Dinner for representatives of the local biotech and high-tech industry corporations to meet a diverse set of graduate students in the College of Natural Sciences who are interested in careers in industry. Graduate students from multiple graduate programs and a handful of faculty members networked with associates from Asuragen, Bioo Scientific, Dell (who generously sponsored this event), IBM, Lab7, Macromoltek, and Sonic Healthcare USA.

We invited 12 industry partners, 12 faculty/staff members, and 24 students. We have found that 8-person tables work well for promoting discussion, so seats were assigned such that every industry partner and faculty member was flanked by two students. Everyone agreed that this seating arrangement works very well for facilitating conversation between people at different career stages and with diverse backgrounds, many of whom had never met.

Based on the many positive and encouraging comments we received most of the attendees, our first formal event with our Industry Partners was a huge success, as it opened many doors for new graduate students interested in different career options and for industry-academia partnerships.

The Industry Partners Dinner. This cocktail hour and dinner provide more than 20 graduate students the oportunity to chat wi th people from the thriving biotech and bioinformatic industry in Austin Texas. Seating was arranged so that Industry partners were flanked by students, providing ample oportunity to learn about graduate research at UT Austin.

The Industry Partners Dinner. This cocktail hour and dinner provide more than 20 graduate students the oportunity to chat with people from the thriving biotech and bioinformatic industry in Austin Texas. Seating was arranged so that Industry partners were flanked by students, providing ample oportunity to learn about graduate research at UT Austin.

Acknowledgments

The Organizers

The symposium and the dinner would not have happened without the efforts of Hans Hofmann (Director of the CCBB) and Scott Hunicke-Smith (Director of the GSAF). BEACONite Laurie Alvarez (CCBB) is a crucial team member who handles all the finances and so much more. Nicole Elmer (CCBB) is an excellent graphic designer and helped design and distribute all communication materials. Thanks to Becca Tarvin and Sean Leonard for helping organize the Industry Partner Dinner. 

The Sponsors

We are grateful to BEACON for providing travel support to BEACON Managing Director Dr. Danielle Whitaker and to The Graduate School Academic Enrichment Fund for providing travel support for Dr. Shelley Berger. Graduate Student Assembly Appropriations were used for printed materials and speaker gifts. We want to extend a special thanks to Dell for generously sponsoring the Big Data in Biology Industry Partners Dinner.

For more information about the Big Data in Biology Symposium, visit the website at http://www.ccbb.utexas.edu/dataconference.html

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BEACON Researchers at Work: What ice cream and biofuels have in common: vanillin and the microbes that eat it

Posted on June 1, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by University of Idaho postdoc Jessica Audrey Lee.

Greetings, BEACON fans. I’m writing from beautiful Moscow, ID, where I work as a postdoctoral researcher in the Marx Lab at the University of Idaho, and where our incubator smells like a cookie factory. It smells that way because the model compound we’re working with at the moment is vanillin, which is not only an important substance in the global food and fragrance industries, but is also a key intermediate in the microbial degradation of lignin.

Oenophiles (of which I am one) may already know this: vanilla-like flavors in wine are almost always a sign that the wine has aged in oak barrels, because oak wood, with its high lignin content, flavors the wine by releasing aromatic bits and pieces of that lignin into it. Foodies (of which I also am one) may also already know this: more than 99% of the vanilla flavoring used today doesn’t actually come from Vanilla planifolium (the vanilla orchid, the source of “real vanilla extract”), but instead is produced industrially either from fossil fuels or from chemical processing of lignin (Walton et al., 2003). And biofuels researchers also know that vanillin (and its derivative, vanillic acid) can be used as a decent stand-in for the monomers that make up the very complex polymer that is lignin.

vanillin_vanillate_MethylobacteriumMy current research is part of a larger project, with collaborators at BU and LBNL, to create a microbial consortium for degrading lignocellulosic biomass (that is, assorted plant parts, some of them woody) into fatty acids that can be used as biofuels. Our consortium will include some of the usual suspects—bacteria from the well-known soil-dwelling genus Streptomyces, and the fatty-acid-accumulating yeast Yarrowia lipolytica—as well as a more unusual player, Methylobacterium extorquens. This Methylobacterium species is typically found on plant leaves—not in the soil, degrading dead plant matter—but we’re introducing it to our consortium because it has a special talent: handling formaldehyde.

Lignin is a difficult compound to degrade, and one of the reasons it’s difficult is that it contains a great number of methoxy (-OCH3) groups. The typical microbial approach for dealing with these methoxy groups is to remove them and turn them into formaldehyde, but the subsequent process of detoxifying the accumulating (very toxic!) formaldehyde can severely slow down lignin degradation (Mitsui et al., 2003). Happily, Methylobacterium, because it typically eats methanol for a living, is very efficient at processing formaldehyde as a metabolic intermediate, so if we could just get it to pull the methoxy groups off of the lignin monomers we could potentially make significant gains in biofuel production from lignocellulose.

M. extorquens (and most Methylobacterium species) carries pink sunscreen-like pigments. M. nodulans, adapted to living in the dark, is white.

M. extorquens (and most Methylobacterium species) carries pink sunscreen-like pigments. M. nodulans, adapted to living in the dark, is white.

This is where the evolution and ecology get interesting. Methylobacterium is in the order Rhizobiales, and therefore not too distantly related to some other plant-associated bacteria that have been shown to degrade lignin, for instance Bradyrhizobium japonicum (Sudtachat et al., 2009) (which can often be found in plant root nodules). In fact, if you compare the two genomes at the locus of the B. japonicum vanillate-demethylating genes (vanAB), you’ll find that all Methylobacterium species also have a gene that looks similar enough to be part of the same pathway (I call it vanA-like). Sadly, M. extorquens can’t demethylate vanillin (hey, it was worth a try—it’s possible we’re the first lab that ever bothered to ask). However, we’ve found that it has a close relative, M. nodulans, that can! We’ve located the M. nodulans gene cluster that we think is responsible, and it seems to have nothing to do with the vanA-like gene that I mentioned earlier; it’s located far away in the genome and doesn’t resemble anything that any of the other Methylobacterium species has (as far as I can tell). What’s even cooler is that M. nodulans is the one species of Methylobacterium that lives not on leaves but in nodules on plant roots. So I suspect that lignin degradation might be a talent it retains specifically because it’s useful in the soil environment.

So, in M. nodulans, we’ve found a great source of lignin-degradation genes for engineering into M. extorquens—a close family member willing to donate an organ, if you will. What I find even more interesting, though, is that at the same time we’re working toward a tangible, potentially industrially important, goal, we also get to peek into the ecology and evolution of some really cool plant-associated bacteria. When several species of a genus diversify to fill radically different niches (leaf versus root), how and when do they pick up the genes they need, or lose the genes they no longer need? I like to think that when we clone a new set of lignin-degrading genes into M. extorquens, we’ll be either restoring a function it once lost, or repeating an acquisition that an ancestor of M. nodulans once experienced. (Which one? I don’t know, but I’m definitely inspired to delve deeper into the phylogeny of these genes across the diverse species that have them.)

We’re likely to follow up cloning with evolution in the lab to help M. extorquens get used to its new genes… and when we do, what kind of changes can we expect to see? I’m new both to experimental evolution and to the metabolism of aromatic compounds, so I have a great deal still to learn. I’m looking forward to finding out more about the evolution has happened in the environment to separate M. nodulans and M. extorquens on the plant, and the evolution that will happen soon in our lab, on the way to creating a microbial consortium for biofuel production.

References

Mitsui R, Kusano Y, Yurimoto H, Sakai Y, Kato N, Tanaka M. (2003). Formaldehyde Fixation Contributes to Detoxification for Growth of a Nonmethylotroph, Burkholderia cepacia TM1, on Vanillic Acid. Appl Environ Microbiol 69:6128–6132.

Sudtachat N, Ito N, Itakura M, Masuda S, Eda S, Mitsui H, et al. (2009). Aerobic Vanillate Degradation and C1 Compound Metabolism in Bradyrhizobium japonicum. Appl Environ Microbiol 75:5012–5017.

Walton NJ, Mayer MJ, Narbad A. (2003). Vanillin. Phytochemistry 63:505–515.

For more information about Jessica’s research, you can contact her at jessicalee at uidaho dot edu.

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BEACON Researchers at Work: The Many “Arms-and-Eyes” of Retinoblastoma Family Proteins

Posted on May 25, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by MSU graduate student Yiliang Wei.

Profile

Hello BEACON members, I’m Yiliang Wei, a graduate student in the Arnosti Lab at Michigan State University (https://arnostilab.natsci.msu.edu). For my first blog at BEACON, I’m going to talk about my study of the functional diversity of the Drosophila Rbf2 protein, a recently evolved Retinoblastoma family member in Drosophila, and its possible role in regulation of ribosome biosynthesis. This study has been recently published on G3 (Genes|Genomes|Genetics) (doi:10.1534/g3.115.019166).

Our lab has been studying Retinoblastoma (Rb) tumor suppressor proteins in Drosophila. Rb proteins function as transcription co-repressors that bind to E2F/DP to control transcription of a diverse set of genes involved in cell cycle regulation. The Rb-E2F pathway plays central roles in cell cycle and development in most eukaryotes. The Drosophila Retinoblastoma family members Rbf1 and Rbf2 are structurally similar to their vertebrate counterparts and possess functionally conserved activities.

A canonical model for Rb-E2F pathway. Rb proteins interact with E2F and DP, and repress target gene expression, such as cell cycle related genes.

A canonical model for Rb-E2F pathway. Rb proteins interact with E2F and DP, and repress target gene expression, such as cell cycle related genes.

Many studies so far have been focused on Rbf1, since it has a dominant role in regulating the cell cycle control and mutants exhibit a lethal phenotype. A few years ago, our lab conducted a genome-wide analysis of the Rbf1 binding profile, and identified a number of non-canonical Rb targets, suggesting diverse functions of Rbf1 besides cell-cycle regulation, such as regulating signaling pathways (Acharya et al. 2012). This aspect of function of Rb appears to be conserved in mammals as well.

On the other hand, the study of Rbf2 has been less intense, mostly due to the mild phenotype and weak transcriptional activity. However, as we turned our eyes to Rbf2, we found some interesting features of this protein. First, the genus Drosophila is different from most arthropods in that it possesses this additional retinoblastoma family member – most arthropod genomes encode a single Rb gene. Second, the Rbf2 protein contains a distinct, derived C-terminus when compared to Rbf1. It is known that the C-terminus of Rb proteins influence regulation and promoter targeting in mammalian systems. These observations led me to consider why the rbf2 gene is strictly evolutionarily retained throughout the Drosophila lineage, despite the modest observed phenotypes; has the Rbf2 protein gained new functions during evolution, and might the unique C-terminus of Rbf2 contribute to differential targeting?

To answer these questions, I carried out parallel ChIP-seq analysis of Rbf1 and Rbf2 in Drosophila embryos. At first, we expected that Rbf2 genome-wide targets might be a subset of Rbf1, based on the canonical Rb-E2F interaction model that Rbf1 binds to both dE2F1 and dE2F2, while Rbf2 binds only to dE2F2. To our surprise, we found that Rbf2 has much more genome-wide targets than Rbf1, and in fact, Rbf1 targets are just a subset of Rbf2. As we noted in our G3 manuscript “this pattern either represents the neofunctionalization of Rbf2 with acquisition of novel gene targets, or alternatively, many of these genes may be bound by the Rbf1 homolog in sister species, with a Rbf2 acquiring some of these interactions through subfunctionalization of Rbf1.” This binding profile of Rbf2 runs contrary to the canonical Rb-E2F model, that Rbf proeins bind to their targets through E2F/DP. Our bioinformatic analysis indicates that Rbf2-only promoters may tend not to have strong E2F-like sites, suggesting that other transcription factors may recruit Rbf2- a property shared with mammalian Rb. In fact, over half of the Rbf2 targets were not associated with E2F binding when compared to another study (Korenjak et al. 2012). It has been noticed that the C-terminal regulatory domains of mammalian Rb proteins partially drive the specificity of these protein interacting with other cofactors. Likewise, the unique C-terminus of Rbf2 may allow it to interact with different types of regulators, other than E2F/DP cofactors.

As we further explored the nature of the bound genes, we found Rbf2 targets have diverse functional groups, similar to what we saw for Rbf1 targets. However, what we didn’t observe in Rbf1 is that the majority of ribosomal protein gene promoters were bound by Rbf2. Unlike the potent Rb activity on cell cycle genes, which are shut down by a small amount of Rb overexpression, the Rbf proteins’ repression activity on ribosomal genes is weaker, but widely spread to the majority of the ribosomal genes. We think that ribosomal protein genes are a different sort of target than cell cycle genes – they typically have less variation in expression levels than developmentally-regulated genes, which can be completely off in many settings. It is possible that the transcriptional regulation of ribosomal protein genes by Rb proteins may be subtle, but we think that it would have pleiotropic consequences. Interestingly, none or very few studies have shown any negative regulatory mechanism for ribosomal protein gene expression, it is rather surprising that this group of genes would be controlled only by positive input. Thus, our study offered an aspect of negative regulatory mechanism of ribosomal protein gene expression.

Intriguingly, one of the few reported phenotypes for rbf2 mutants may tie into the negative regulation ribosomal protein gene expression: rbf2 null flies lay eggs at a considerably higher rate than wild-type ones. This mild phenotype has been neglected, however, the egg laying is in fact tightly coupled to nutritional signals. Though it may sound good, laying too many eggs under certain conditions may have long-range fitness effects, perhaps reducing lifetime fertility. Therefore, Rbf2 may regulate Drosophila reproduction by fine-tuning the biosynthetic components, such as ribosome protein gene family.

An overlooked aspect of previous ChIP sequence data relating to human Rb and related p130 and p107 proteins is their similar enrichment on ribosomal protein promoters (Chicas et al. 2010). Interestingly, the mammalian Rb proteins are known to directly regulate RNA polymerase I and III activity. Together with the ribosomal protein gene regulation, this multi-layer gene regulatory network cover all aspects of ribosome production – what we usually consider as a potent break switch on cell cycle genes may also be regulating by numerous, subtle contributions the biosynthetic capacity of a cell. Clearly an activity relevant to cancer cells! Our findings provide a new view of the impact of Rb proteins in cancer.

Just like the Kuan-yin of a Thousand Arms, with each hand holding a unique power, the Rb family proteins have reached their “arms” to many aspects of the gene regulatory network. (Picture from The Palace Museum, http://www.dpm.org.cn)

Just like the Kuan-yin of a Thousand Arms, with each hand holding a unique power, the Rb family proteins have reached their “arms” to many aspects of the gene regulatory network. (Picture from The Palace Museum, http://www.dpm.org.cn)

As it turns out, 5000 years of Chinese culture provides an apt analogy for the action of the Drosophila Rbf proteins. Like Kuan-yin of a Thousand Arms and Eyes from Chinese Buddhism culture, where each hand holds a unique power, the Rb family proteins have reached their “arms” to many aspects of the gene regulatory network. Our studies of Rbf proteins indicate that there are many more functions of Rb, as well as non-canonical mechanisms that recruit Rb proteins to their targets. The appearance of the novel Rbf2 protein on the genome landscape, just as the more recently derived human Rb protein, indicates that gene duplication and diversification contributes to these central processes.

References:

Acharya, P., N. Negre, J. Johnston, Y. Wei, K. P. White et al., 2012 Evidence for autoregulation and cell signaling pathway regulation from genome-wide binding of the Drosophila retinoblastoma protein. G3 (Bethesda). 2: 1459–1472.

Chicas, A., X. Wang, C. Zhang, M. McCurrach, Z. Zhao et al., 2010 Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 17: 376–87.

Korenjak, M., E. Anderssen, S. Ramaswamy, J. R. Whetstine, and N. J. Dyson, 2012 RBF binding to both canonical E2F targets and noncanonical targets depends on functional dE2F/dDP complexes. Mol. Cell. Biol. 32: 4375–87.

Wei, Y., S. S. Mondal, R. Mouawad, B. Wilczynski, R. W. Henry et al., 2015 Genome-Wide Analysis of Drosophila Rbf2 Protein Highlights Diversity of RB Family Targets and Possible Role in Regulation of Ribosome Biosynthesis. G3 (Bethesda). In press.

For more information about Yiliang’s work, you can contact him at wyliang1987 at gmail dot com.

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BEACON Researchers at Work: Explain it to me like I'm a four-year-old.

Posted on May 18, 2015 by Danielle Whittaker

This week’s BEACON Researchers at Work blog post is by University of Washington graduate student Sonia Singhal.

Sonia Singhal, Carrie Glenney, and Brian Connelly in front of the activity table at the Pacific Science Center's UW-centric "Paws-On-Science" event.

Sonia Singhal, Carrie Glenney, and Brian Connelly in front of the activity table at the Pacific Science Center’s UW-centric “Paws-On-Science” event.

How do you know that you understand a scientific concept?

When you can explain it to a four-year-old.

While this is not a situation I encounter in my day-to-day work, studying viral evolution in Dr. Ben Kerr’s lab at the University of Washington, I do face it frequently as a Science Communication Fellow with the Pacific Science Center. On a Saturday morning every couple of months, I take the bus down to Seattle Center, and in the bright, airy Ackerly Gallery of the Pacific Science Center, I set up a table with boxes of colored beads and sheaves of colored paper. These items form the backbone of the activities I am developing to teach visitors to the Pacific Science Center about evolution.

I run two activities. The first activity, which demonstrates mutation, is a drawing game. Visitors choose a simple line drawing and copy it as many times as they can in one minute. I then encourage them to tell me how their drawings compare to the original drawing. The second activity demonstrates selection. I set up boxes with colored beads, representing bacteria with different traits. Each box contains beads of predominantly one color, with a few beads of other colors mixed in. Visitors pour out the beads and notice the different colors. They then explore how the different colors – the different traits – are important by choosing colored paper backgrounds (antibiotics) that will “kill” beads with a matching color.

The activities have been designed so that any visitor to the Science Center, regardless of their age or background, could learn from them. However, I find that I get mostly 4- to 11-year-olds visiting my table. Interacting with them is demanding, hectic, frustrating, great fun, and incredibly rewarding, often all at once. Some of the children take their time copying a few pictures; some of them get into the game and make so many copies that they run out of room on the page. Some of them like to color-code their beads after pouring them out. Some of them want to pour out every bead from every box to make a multicolored bead soup. Some of them want to take home the boxes, or the beads, or the colored pieces of paper, or even the plush microbes that I bring in from my advisor’s office as props. But they all love making drawings and playing with the beads. Even when I don’t feel I’m getting my point across, I have fun watching them have fun.

The children teach me as much as – if not more than – I teach them. Working with them forces me to explain my research without jargon, and for a 4-year-old, this includes words like “bacteria” and “reproduce”. It stretches me to think of analogies between my research and the children’s everyday lives. For example, I will explain to them that bacteria copy themselves, and sometimes those copies look a little different from the parent, “just like you look a little different from your mom or your dad.” Most importantly, working with children challenges my assumptions. The media is rife with evolutionary stories involving antibiotic resistance and emerging diseases, so to those of us working in experimental evolution, viruses and bacteria are obvious examples of evolution in action. However, most of the children at the Pacific Science Center do not understand that viruses and bacteria replicate; they view germs as static forces rather than dynamic populations. And it turns out that this single point is a key hinge for explaining evolution. If the microbes are not copying themselves, they have very few avenues for dramatic changes.

The Pacific Science Center believes in giving its visitors freedom to explore. As in a typical museum, there are placards to read, but there are also levers to pull, wheels to spin, pressure pads to jump on, and water nozzles to aim at moving parts. In the same spirit, I let the visitors decide which activity they want to try. Usually they only choose one or the other, but sometimes I can take them through both and watch them fit the two activities together. One young girl decided that she wanted to draw, so we went through the drawing game; then she decided that she wanted to know what was going on with the colored boxes, so I had her choose one and pour out the beads. “Not all of them are pink,” she noticed. I told her, “That’s right. Just like you made copies of that drawing, these germs are making copies of themselves. And just like your copies were all a little different, the germ copies are a little different too.” “Oooohhh,” she said, with the intonation of a “eureka” moment.

The activities are flexible enough that I can layer in additional details. One boy liked the bead activity so much that he played it three times in a row. The fourth time, I asked if he wanted to try something a little different. “This time,” I said, “let’s give this person medicine before he gets sick, rather than after he gets sick.” I had him pour the beads directly onto the colored background, rather than adding the background afterwards. He immediately responded differently to the activity. Where before, he would dump out all the beads at once, now he shook them out a few at a time and stopped every four or five beads to remove the ones that matched the background color. He understood that, since the environment was different, the population of beads that were able to “survive” was also different.

My most interesting interactions, though, occur when the children bring their own questions to me. One girl, who already knew a little bit about disease-causing microbes (“Germs can infect people, or dogs, like parvo,” she told me.), asked a lot of detailed questions about how our bodies fight disease off, and how microbes can hide from immune cells. Another girl and her younger sister wanted to know whether mice were vertebrates or invertebrates. I had to shift gears abruptly to rack my microbe-centered brain for examples of common vertebrates and invertebrates. By the end of our conversation, I was explaining to them the difference between an endoskeleton (an internal skeleton, such as we have) and an exoskeleton (an external skeleton, such as insects have).

Working in an academic research lab requires understanding the minutiae of one’s question, organism, and experiments. At the same time, this fine focus can impede us from communicating the salient points to a non-scientific audience. My work with the Pacific Science Center gives me a way to step back, review the broader context of my research, and decide what is truly necessary for understanding. Although I’m still working out how best to present and explain evolution, I feel that every iteration of my activities brings me a little closer.

For more information about Sonia’s work, you can contact her at singhal at myuw dot net.

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Tortoises, hares, and topography: how fitness landscape structure affects the speed of adaptation

Posted on May 13, 2015 by Danielle Whittaker

NahumHello fellow BEACONites and interested members of the public, I’m Josh Nahum, a postdoctoral fellow, who was at the University of Washington during the early years of the Beacon Center, but now I’m doing research at Michigan State University (more info found here: http://beacon-center.org/blog/2012/03/29/introducing-beacon-distinguished-postdoctoral-fellow-joshua-nahum/). I do digital and microbial evolutionary experiments, and some of my previous work involved the evolution of prudence in E. coli was covered on this blog is the past (http://beacon-center.org/blog/2011/08/29/beacon-researchers-at-work-survival-of-the-weakest-when-doing-poorly-does-best/). Similar to my previous post, today I’m going to talk about how spatial structure affects evolving populations. 

All living things rely on evolution by natural selection to become better adapted to their environment. The process of adaptation requires mutations (changes in DNA) that improve their reproductive success (called fitness) to be present in order to be selected. However, other research has shown that beneficial mutations can interfere with each other. This interaction (called epistasis) can constrain adaptation and make it more difficult to become well adapted. Studying this effect is important, as understanding (and predicting) evolution affects our ability to anticipate changes in evolving populations. This is useful in planning for the evolution of disease (such as the flu), mitigating the evolution of antibiotic resistance, and predicting how populations will respond to climate change. 

To investigate how evolution is constrained by epistasis (whether a mutation’s effect on fitness is adversely related to the presence of other mutations), we employ a common visual metaphor in evolutionary biology: the fitness landscape. In a fitness landscape, potential genotypes (specific possible DNA sequences) are envisioned as a surface, where genotypes that are just one mutational step from each other are adjacent. The fitness of each genotype is represented by the elevation of that point in the landscape. Thus a genotype with a high elevation is more likely to reproduce. A population consists of a cloud of points on the surface of this landscape, each point being a single organism’s genotype. Mutation adds new genotypes to the population, often causing cloud to spread. Natural selection operates to remove low fitness genotypes (organisms at lower elevation), leading the cloud to increase in average fitness (elevation in the metaphor) over time. If the cloud of genotypes reaches the highest location in the fitness landscape, then the population it represents is optimally adapted to its environment.

Similar to the Aesop's fable of the Tortoise and the Hare, more structured populations begin adapting more slowly, but can ultimately outpace less structured populations in the long run. Image attribution Project Gutenberg.

Similar to the Aesop’s fable of the Tortoise and the Hare, more structured populations begin adapting more slowly, but can ultimately outpace less structured populations in the long run. Image attribution Project Gutenberg.

Our work addresses the fundamental question of whether the fitness landscape is smooth or hilly. If a landscape is hilly, populations that possess genotypes that place them at the top of a hill (a location where all nearby mutations decrease fitness) will be trapped there, because any mutants that go down the hill will be outcompeted by those at the top. This is a problem if there exist taller hills a long way away. The genotypes that the peaks of these hills represent possible individuals that would be better adapted to the environment, but the current population has no way of evolving toward them. This problem doesn’t exist if a landscape is smooth (having just one hill), as all adaption leads to the global optimum (the best adapted genotype).

In nature, populations can be spread across an environment in a variety of patterns. Some of these patterns make it easy to migrate from one part of the population to another, while others make it challenging. Easier migration allows for beneficial mutations to spread through the population, while decreased mutation slows this process.

Interestingly, we can use this property to determine how hilly an adapting species’ fitness landscape is. If the fitness landscape is smooth, populations will evolve to the same optimal genotype, regardless of how easy migration is, although populations with more migration will get there faster. However, in hilly landscapes, populations can become trapped on various different fitness hills. A population with lots of migration is likely to all get trapped on the same hill, because beneficial mutations will sweep across it shortly after they first occur. Populations with limited migration, on the other hand, will likely reach a wider variety of peaks, as different beneficial mutations sweep through different parts of the population. This means that the population will evolve slower, but can better adapt to its environment because some of the explored peaks may be higher in fitness than the peak discovered by a less structured population. We name this effect the Tortoise-Hare Pattern; the population with less migration (Tortoise) initially evolves slower than the population with more migration (Hare). However the Hare can become trapped at a suboptimal fitness peak, allowing the Tortoise to surpass it in fitness and win the “race”.

Adaptation of E. coli populations over time demonstrating the Tortoise-Hare Effect. Along the x-axis is the number of transfers made during the experiment (a.k.a. time). The y-axis is the relative fitness of evolved populations compared to the ancestor (fitness = 1 means the same fitness as ancestor, but fitness > 1 means better adapted than ancestor). The restricted migration treatment (slow migration, Tortoise) is in green and initially adapted slower than the unrestricted migration treatment (easy migration, Hare) as denoted the asterisks indicated significant differences between populations. But in the later transfers, the restricted treatment out-adapts the unrestricted treatment leading to a Tortoise-Hare Effect and the implication of a rugged landscape. For details see linked paper at the end of this post.

Adaptation of E. coli populations over time demonstrating the Tortoise-Hare Effect. Along the x-axis is the number of transfers made during the experiment (a.k.a. time). The y-axis is the relative fitness of evolved populations compared to the ancestor (fitness = 1 means the same fitness as ancestor, but fitness > 1 means better adapted than ancestor). The restricted migration treatment (slow migration, Tortoise) is in green and initially adapted slower than the unrestricted migration treatment (easy migration, Hare) as denoted the asterisks indicated significant differences between populations. But in the later transfers, the restricted treatment out-adapts the unrestricted treatment leading t

o a Tortoise-Hare Effect and the implication of a rugged landscape. For details see linked paper at the end of this post.

The presence of a Tortoise-Hare Pattern indicates that the fitness landscape is hilly (as the Hare would always win in a smooth landscape). We first used a digital model to confirm that the Tortoise-Hare Pattern is a litmus test for landscape hilliness. Afterwards we performed experiments with the gut bacteria, Escherichia coli, and found a Tortoise-Hare Pattern when we experimentally manipulated migration rates in a laboratory-based evolution experiment. We divided multiple populations of E. coli each into a grid of 96 subpopulations and had migrations occur between neighboring subpopulations (slow migration) or between any other subpopulation regardless of distance (easy migration). Finding evidence of landscape hilliness in a bacterial system implies that other living things are evolving on hilly fitness landscapes as well. 

Too Long Didn’t Read (TLDR):

We experimentally evolved Escherichia coli populations, divided into smaller sub-groups, to explore whether more spatially restricted migration allows populations to achieve better adaptations. We found that limiting migrations between sub-groups does in fact yield greater fitness improvements, at the cost of slowing evolution. We name this the Tortoise-Hare pattern, as it is the slow-and-steady population with low migration that ultimately wins the fitness race.

For further reading there is a MSU press release concerning the work found here (http://msutoday.msu.edu/news/2015/tortoise-approach-works-best-even-for-evolution/). And, the paper corresponding to this work is recently published in PNAS found here (http://www.pnas.org/content/early/2015/05/06/1410631112.abstract, doi: 10.1073/pnas.1410631112). Unfortunately, the paper is behind a pay wall, but you can see a draft of the manuscript on bioRxiv (http://biorxiv.org/content/early/2014/06/03/005793) or email me at nahumjos@msu.edu.

 

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BEACON Researchers at Work: Perspectives on Evolutionary Medicine and Public Health

Posted on May 11, 2015 by Danielle Whittaker

MSU LBC Students Attend Inaugural Meeting of the International Society for Evolutionary Medicine and Public Health

Tempe, AZ, March 19-21, 2015

On Thursday March 19, 2015, six MSU Lyman Briggs College students, accompanied by Dr. Jim Smith (LBC Biology), traveled to Tempe, Arizona to attend the inaugural meeting of the International Society for Evolutionary Medicine and Public Health (EMPH). The meeting, held at the Tempe Mission Palms Hotel, brought together nearly 200 research scientists and physicians committed to the idea that evolutionary thinking can help us better understand human health and disease. 

The trip was made possible for our students by generous support from the Lyman Briggs College, the MSU Honors College, and the NSF-funded BEACON Center for the Study of Evolution in Action.

One highlight of the trip was our encounter with LBC alumna Dr. Julie Horvath (Lyman Briggs Zoology, 1996), who is currently Research Associate Professor of Biology at North Carolina Central University and Director of the Genomics & Microbiology Research Laboratory at the North Carolina Museum of Natural Sciences.

As a part of the trip, each student was asked to write a “blog post” in the form of a description of his/her journey from both an intellectual and experiential standpoint. What follows below is what each student wrote.

Our group in front of the Tempe Mission Palms Hotel. From left to right: Ryan Owen, Justin Jabara, Collin Stapleton-Reinhold, Jim Smith, Julie Horvath, Andrew Benner, Lauren Mamaril, and James Conwell.

Our group in front of the Tempe Mission Palms Hotel. From left to right: Ryan Owen, Justin Jabara, Collin Stapleton-Reinhold, Jim Smith, Julie Horvath, Andrew Benner, Lauren Mamaril, and James Conwell.

Andrew Benner

The presentation that moved me the most was by Dr. Erida Gjini’s, entitled “Integrating antimicrobial therapy with host immunity to fight resistant infections: classical vs. adaptive treatment.” Dr. Gjini, a post-doctoral researcher at the Instituto Gulbenkian de Ciencia in Portugal, combined clinical, experimental, genetic, and epidemiological strategies to formulate a mathematical model to analyze and calculate optimum levels of antibiotic treatment. The adaptive treatment model analyzes an array of variables, including symptom threshold, proper dosage, timing, and duration of treatment. The incredible finding was that synergistic clearance by drug and host immunity optimizes treatment outcomes. That means that rather than using a massive amount of antibiotics, a more moderate treatment allows the human body to intertwine its immunological functions with the antibiotic, working together to produce a more successful, unified treatment. Dr. Gjini’s research and mathematical model were eye opening for me with respect to analyzing and predicting the optimal level of antibiotic dosage, treatment timing, and host immune response.

The social aspect of our attendance at the meetings was equally rewarding. Although demanding and extremely dense in scientific jargon, the bits and pieces of understanding proved to be an irreplaceable exposure to evolutionary medicine and professional research in general. An aspect of the trip that I did not anticipate was my interaction with my classmates, as well as the professionals at the conference. I was able to gain insight on the lives of my classmates and the researchers that were present, aside from just an academic understanding. Although we still had conversations about the lectures we were attending and relative coursework/research interests, it was an experience in itself getting to know my peers outside of the confines of the classroom.

James Conwell

While there were a number of fascinating presentations at the Evolutionary Medicine Conference, one really stood out for me. Mr. Casey Roulette, a Ph. D. candidate at Washington State University, gave a presentation on the effect of plant drug use in humans, and its relationship with human parasites. In his research, he was able to follow a group of people in the Central African Republic to test the relationship between the number of gut parasites that they had and their drug use. His research indicated that those that were using tobacco or marijuana had lower amounts of gut parasites compared to those in the population who did not use those drugs. I later spoke with Mr. Roulette about his research, and we discussed drug use in our culture, and the possibility of drug users having allergies, as there may be a link between IgE and drug use. It was a fascinating concept for me to think about, and I am now writing my senior research paper on the relationship between allergies and drug use. 

While the conference itself was fantastic, one of the neater points was having the opportunity to connect with my classmates who attended, as well as meet other professionals in the field, and get to know them personally. The directors of the conference did an excellent job of getting everyone out in the beautiful Arizona sunshine, and encouraging others to meet, and to learn a bit about them. One great opportunity to meet others was how all of the meals at the conference were outside, in a break from the professional setting, and the options for eating were endless. Beyond this, a man named Baba Brinkman rapped about Evolutionary Medicine, and it was a fun way to think about the content of the conference. Everybody laughed, and had a great time at his show.

Justin Jabara

During the Evolutionary Medicine conference there were many interesting presentations but one was of particular interest to me. Dr. Charles Nunn from Duke University gave a presentation on the evolution of sleep that focused on how humans compare to other great apes. One of the conclusions of the study was that of the great apes (humans included) we sleep the least out of any ape. In contrast to this reduced sleep time, we spend more time in REM sleep than any other great ape. This is important because sleep plays such a critical role in health and happiness. For example, when a patient suffering from depression begins pharmaceutical antidepressant therapy, REM sleep greatly decreases. This is because antidepressants target monoamines, which mediate sleep cycles. Applying findings of evolutionary medicine to medical problems such as this one can lead to novel ways of thinking about diseases and could lead to progress in their medical treatments.

We had a blast in Arizona. After the conference was over we found the hotel pool and soaked in the sun. It was awesome having 90°F weather in March. We also made friends with people at the conference. One person we met was Will from Newcastle University, who was in his final year of medical school. We ended up spending quite a bit of time with him and became friends. We even travelled via Uber to an awesome desert botanical garden a few miles north of Tempe. Overall, the trip to Arizona was a smashing experience!

Lauren Mamaril

My experience at the International Society for Evolution, Medicine & Public Health meeting in Tempe, AZ was a first of its kind for me. One of the presentations I found most interesting included an evolutionary standpoint of natural birth and Caesarian section, presented by Dr. Wenda Trevathan from New Mexico State University. Dr. Trevathan examined excessive C-section rates in various countries, and suggested that relationships exist between the rise in C-section and the rise in HIV, obesity, diabe

tes, and maternal age. Also, with elective C-section, she brought to light that an infant does not receive the same gut microbiome from its mother compared to babies born by vaginal birth. Dr. Trevathan also examined tocophobia (the fear of vaginal delivery) and suggested that the anxiety and pain experienced during childbirth may be evolutionarily advantageous. She implied that providing emotional support through the birth experience may be healthier than elective C-section.

The Mission Palms at Tempe conference center was a beautiful facility featuring a courtyard and numerous orange trees, and only contributed even more positively to the opportunity. I had the unique opportunity to meet with many of the pioneers of this field, including Dr. Randolph Nesse, President of the International Society for Evolutionary Medicine and Public Health. Having this experience with my fellow classmates allowed me to get to know them better compared to just being in a classroom setting. It was cool to see what their interests in medicine are, what makes them click, and which particular presentations struck them the most in comparison to my own interests.

Ryan Owen

One of the more intriguing talks I attended was by Dr. Ruslan Medzhitov, Professor of Immunobiology at Yale University. He described two types of mechanisms that contribute to a healthy state: maintenance mechanisms and curing mechanisms. The former generally operate until they are not needed anymore, and this makes sense. Our lifespan has been defined by extrinsic mortality factors for our entire ancestral history, and therefore these maintenance programs have evolved accordingly. However, modern medicine has allowed humans to live far past ages that our bodies are evolved to, and these mechanisms are not adequately evolved to deal with the health consequences. We have to approach curing disease from an evolutionary perspective, understanding what is causing the disease state: is it a maintenance malfunction or a curing malfunction? Our bodies have evolved natural solutions to curing malfunctions that can be utilized by finding the right “button” and pushing it (statins, beta-blockers, etc.). If the disease does not have a defense that has naturally evolved (i.e., cancer), then we need to stop looking for curing mechanisms and start searching for ways to upregulate our maintenance mechanisms.

 The experiential highlight for me was being able to see Arizona for the first time. The trip was a great balance of academia and leisure, and it allowed for some exploration around a state I had never seen before. The learning went beyond the conference as I was able to take in a lot about the culture and the people through talking to locals, indulging in the cuisine, exploring the Desert Botanical Gardens, and hiking the incredible land formations.

Collin Stapleton-Reinhold

The one presentation that I enjoyed the most was by Dr. Stefan Ruhl from the University at Buffalo. What stood out about his presentation was that he wasn’t your normal researcher. He was a dentist and his team was looking at the different kinds of proteins found in saliva in humans, chimps and gorillas. Even though they found many proteins that were linked in the same way throughout all three species, the interesting thing was they found multiple proteins that were different enough to be looked into further. They also found that human saliva is a lot more watery than chimp or gorilla saliva, which they reasoned might cause those species to be able to eat a more cellulose dense diet. In all, they found many different proteins that were different among all three species, which could indicate that saliva is a hot bed for evolution and that we should do more research in the field to see if those changes can be linked to any other evolutionary changes that we many have with our closest non-human relatives.         

I loved how the directors of the conference had all of our meals outside and the spread was out of this world. You could fill up a plate and still not have gotten everything that they offered. If that wasn’t enough, after everything was over on Friday night, Baba Brinkman rapped about evolutionary medicine. It was spot on. To make things even more enjoyable, he had dancers come up for one of his songs and dance in front of everyone there for his show. After multiple shoves and nagging from my fellow Briggsies, I became one of the dancers and it is a memory I will never forget. 

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