Studying patterns in bacterial organization

credit to Gerard Wong, of the California NanoSystems Institute

credit to Gerard Wong, of the California NanoSystems Institute

by Olivia Zhu

Bacterial biofilms, at first glance, may seem to be spontaneous, random phenomena from which we have no power to protect our environment or ourselves.

They’re potentially useful as an aid to wastewater treatment, but they also cause infections that account for $6 billion a year in health care costs. Biofilms are also more resistant to antibiotic drugs, making them difficult to eradicate.

Dr. Kun Zhao, of the California NanoSystems Institute at UCLA, refuses to see biofilms as arbitrary: he emphasizes the fact that biofilms are communities of bacteria in self-produced polymeric matrices of polysaccharides, and using a biophysical approach, he studies the pattern behind their organization.

Central questions in Zhao’s research include how bacterial colonies transition from reversible to irreversible attachment, how they migrate, and how they ultimately disperse. Specifically, Zhao examines the polysaccharide Psl, which poses a positive feedback loop because it is both secreted by moving bacteria and serves as a chemo-attractant for future bacteria movement. The positive feedback creates an inherent pattern, as bacteria are more likely to visit a location they have been to before.

Zhao and colleagues have also discovered that bacterial mutants that cannot produce Psl exhibit more random and uniform movement.

To better quantify bacterial movement,Zhao has created a computer algorithm that shows the full movement history of each individual bacterium on a dish, and that provides a “search engine” allowing researchers to find every bacterium performing specific life cycle activities, like division.

Zhao has postulated a “rich get richer” mechanism for biofilms. He compares bacterial organization to Wall Street because concentrated movement ensures that some cells become extremely enriched. In the future, he hopes to model colloidal structures for biological problems, like the growth of the bacterial cell wall. Zhao currently uses colloids, which in physics are used as models for atomic systems, to observe how shapes affect self-assembly. He also would like to look at cell-substrate interactions, which are implicated in bacterial territoriality and social interactions.

Messenger of Pain Identified

Pain researcher Ru-Rong Ji is a distinguished professor of anesthesiology and professor of neurobiology.

Pain researcher Ru-Rong Ji is a distinguished professor of anesthesiology and professor of neurobiology.

By Karl Leif Bates

In their pursuit of understanding how pain works at the molecular level, a research team lead by Ru-Rong Ji of anesthesiology and neurobiology has found a new function for MicroRNAs, short stretches of genetic material that signal genes to turn on or off.

In a paper appearing online April 2 in the journal Neuron, Ji and his colleagues in the Pain Signaling and Plasticity Lab describe one MicroRNA called “let-7b” that is found floating outside cells and can bind specifically to pain-sensing neurons.

Let-7b rapidly excites these neurons through the toll-like receptor-7 (TLR7) and its associated ion channel, TRPA1, which leads to a rapid inward flow of ions to the neurons.

Injecting the 22-basepair RNA molecule into the feet of mice induced a sensation of pain within minutes. (The mice are seen lifting the affected paw or licking it.)

The MicroRNA let-7b is the 22 red nucleotides in this diagram. (Image from MiRNAMap site, Institute of Bioinformatics National Chiao Tung University, Hsinchu, Taiwan.)

The MicroRNA let-7b is the 22 red nucleotides in this diagram. (Image from MiRNAMap site, Institute of Bioinformatics National Chiao Tung University, Hsinchu, Taiwan.)

Mutant mice missing the genes for TLR7 and TRPA1 were found to be less susceptible to the signaling molecule or even unaffected by it.

Pain is notoriously difficult to measure, but Ji said the new molecule may serve as a biomarker for pain. “We’re also interested to know if targeting this miRNA would be a way to alleviate pain.”

The study was supported by NIH grants R01-DE17794, R01-DE22743, and NS67686 to Ru-Rong Ji and R21-NS82985 to Zhen-Zhong Xu.

CITATION: “Extracellular MicroRNAs Activate Nociceptor Neurons to Elicit Pain via TLR7 and TRPA1,” Park, Xu, Berta, Han, Chen, Liu and Ji. Neuron, Online April 2, 2014. DOI: 10.1016/j.neuron.2014.02.011

 

Discovering “CRISPR” methods for genetic recombination

Screen Shot 2014-03-27 at 9.54.19 PM

By Olivia Zhu

In a lecture to an overflowing auditorium in the Bryan Research Building on March 27th, Dr. Jennifer Doudna, of the University of California, Berkeley, unraveled her story of research into CRISPRs, or “clustered regularly interspaced short palindromic repeats.” Dr. Doudna specializes in RNA; she started her project on CRISPRs seven years ago, when CRISPRs were denounced as no more than junk.

The CRISPR method includes a modifiable RNA sequence whose function is to recognize target sequences on DNA. The RNA also includes a target sequence that induces cleavage by the associated protein, CAS9. CAS9 introduces double-stranded breaks and represents an exciting improvement over the previous, less efficient collection of nine proteins used to cleave DNA; the breaks make room for insertion of new genes. The CRISPR-CAS9 system has inserted genes into a wide range of organisms, including bacteria, yeast, nematode worms, fruit flies, plants, fish, mice, and even human cells.

Jennifer Doudna

Jennifer Doudna of UC Berkeley and the Howard Hughes Medical Institute

While researchers are actively investigating the possibility of using CRISPR technology to alter genes, Doudna said the mechanism behind CRISPR gene editing remains unclear. For example, it seems extraordinary that the CRISPR-CAS9 system can locate and unwind specific DNA sequences in human cells, as the DNA there is highly condensed around histones and methylated.

Doudna’s lab is working to understand the details of the CRISPR process. One current hypothesis includes the idea that there is a spring mechanism that allows the CAS9 protein to effectively cleave DNA strands.

Nevertheless, CRISPR technology has been instrumental in allowing more precise and efficient genetic modification. What we once considered junk has spurred substantial advances across various fields of science.

Rhyne King: Unearthing an Ancient Religion

rhyne

By Olivia Zhu

Rhyne King, a senior from Greensboro, North Carolina, plunges into the depths of history to retrieve remnants of long-past civilizations.  Rhyne is currently writing his senior thesis on the religion of the Achaemenid Empire of Persia, which existed in modern day Iran until 330 B.C.E., when Alexander the Great’s army conquered it.  Specifically, Rhyne is focusing on what the Achaemenid religion was and how the Achaemenids treated foreign religions.  Rhyne says that it is rather difficult to directly compare the Achaemenid religion to any modern religion, but that some imagine it to be similar to Zoroastrianism.

Rhyne’s skill set and dedication to his research are extraordinary in and of themselves.  After spending the summer studying with Professor Jacques Bromberg, Rhyne added the skill of reading Old Persian to his repertoire of languages, which includes Latin, Greek, and Persian.  He uses Old Persian, the language of the Achaemenid kings, to read inscriptions about their religion.  Rhyne has also traveled to the British Museum in London to inspect Achaemenid inscriptions and art.

An inscription Rhyne studied at the British Museum

An inscription Rhyne studied at the British Museum

Rhyne pioneers investigation into the Achaemenid empire by balancing Greek accounts, which currently form a majority of the body of knowledge about the civilization, with Persian sources.  He says that up to this point, historians have not reconciled the two sources systematically.  Rhyne is particularly fascinated by the Achaemenid empire’s tolerance of religion.  He emphasizes, however, that their tolerance, immortalized in the Cyrus inscription from Babylon, was not an ancient declaration of human rights; rather, it was the system that proved most convenient for them.

Throughout his four years at Duke, Rhyne has also served as president of the Round Table selective living group and the Latin Club, and he has played for the marching band.  Rhyne plans to continue researching the Achaemenid Empire in graduate school, and to someday become a professor.

Grad Student Solves 30-Year-Old Physics Problem

By Erin Weeks

Sometimes an age-old question just needs a fresh set of eyes.

That was the case in Duke’s physics department, where a graduate student and professor recently resolved a calculating dilemma that has vexed computational physicists for decades.

Emilie Huffman, second year PhD student in physics

Emilie Huffman, second year PhD student in physics

Emilie Huffman is a second-year PhD student from Charlotte, North Carolina. Last spring she began working with Shailesh Chandrasekharan, an associate professor and the director of graduate studies in physics, on what’s known as a sign problem.

Chandrasekharan is a theoretical nuclear and particle physicist who specializes in solving sign problems, which arise when one uses certain computational algorithms to calculate the behavior of large numbers of particles called fermions.

“Almost all the matter we know of are made with fermions,” Chandrasekharan said. “As building blocks of matter, it’s very important to be able to do calculations with them.”

But calculations of such complexity get tricky, and sign problems make it easy for wrong results to surface.

“It’s a very broad problem that affects almost all fields of physics involving quantum mechanics with strong correlations, where Monte Carlo methods are essential to perform calculations,” Chandrasekharan said.

Some in the field have simply moved on since the 1980s, leaving interesting questions plagued by sign problems unexplored. Other scientists have found workarounds and approximations. Very few, including Chandrasekharan, have tried to figure out solutions through the years. Huffman began work to expand on one of her advisor’s solutions, involving a grouping concept called fermion bags, and apply them to a new class of problems.

“She finally figured out a nice formula,” Chandrasekharan said. “Although the formula is quite simple and elegant, I couldn’t guess it.”

“In physics, often there’s a truth, and if you’re hitting on the right truth, everything starts falling into place.” Chandrasekharan says that’s what happened when he began applying Huffman’s formula to a class of problems.

Their paper appeared recently in the journal Physical Review B’s Rapid Communications.

“Now that I have a solution, I can begin to apply it,” Huffman said. Starting with condensed matter physics, Huffman plans to apply her solution to various questions that have been stymied by sign problems. “I can use this solution to study properties of graphene,” she said, referring to the single-layer carbon that has been touted as the strongest material in the world. Many puzzles remain in the field, especially involving multi-layer graphene sheets.

Wherever she turns her attention next, it’s clear Huffman has a promising career ahead.

Citation: “Solution to sign problems in half-filled spin-polarized electronic systems,” Emilie Huffman and Shailesh Chandrasekharan. Physical Review B Rapid Communications, March 12, 2014. DOI: 10.1103/PhysRevB.89.111101.

 

Some Animals Move Through The Treetops With Help From A Stiff Back

Guest post from Robin A. Smith, Duke Lemur Center

Some tree-dwelling animals move through the forest with the help of an unlikely tool — a stiff back. A more rigid spine seems to help  stabilize their trunks as they reach across gaps in the canopy, according to Duke researchers.

Slender Loris

The slender loris (Loris tardigradus) is able to exploit tender tips of tree branches by moving slowly and keeping a stiff back rather than leaping from branch to branch. (Credit: David Haring, Duke Lemur Center)

The findings appear in the March 2014 issue of the Journal of Morphology.

Animals that live in the treetops need to be good at crossing gaps between trees in order to move and forage in the canopy without constantly climbing up and down. Some animals leap, hop or bound from branch to branch, flying through the forest in a feat of aerial acrobatics. But others move more slowly and deliberately, reaching out and grabbing onto the tips of the nearest tree to form a bridge and pulling themselves across.

The latter strategy helps some animals venture onto slender branch tips where young leaves and fruits are often found –- perches that are too thin and delicate to leap off without buckling, said lead author Michael Granatosky, a grad student in Evolutionary Anthropology.

To investigate the anatomical traits that help some animals bridge rather than bound between branches, Granatosky and colleagues pored over skeletons in museums and took measurements of the spines and ribs of 22 species — including lemurs, treeshrews, anteaters, opossums and squirrels. Some of the species move slowly and cautiously through the treetops, while others leap and jump.

The researchers also analyzed the bridging behavior of two pairs of closely-related species – the bare-tailed woolly opossum versus the gray short-tailed opossum, and the fat-tailed dwarf lemur versus the slender loris — while the animals negotiated custom-made jungle gyms.

The opossum study was part of a previous experiment by co-authors Daniel Schmitt and Pierre Lemelin at Duke, and the primate study was conducted at the Duke Lemur Center.

The researchers found that the species that bridged more often, or for longer periods of time, had narrower spaces between adjacent ribs and vertebrae.

Their more tightly-woven spines limit their ability to bend side-to-side, but enable them to hold their body out straight to span openings in the canopy without relying on brute muscle strength alone, Granatosky said.

The study was funded by the Force and Motion Foundation and by a National Science Foundation Graduate Research Fellowship to Michael Granatosky.

CITATION: “Functional and evolutionary aspects of axial stability in Euarchontans and other mammals,” Granatosky, M., et al. Journal of Morphology, March 2014. DOI: 10.1002/jmor.20216. http://onlinelibrary.wiley.com/doi/10.1002/jmor.20216/abstract

Seeing may not be perceiving—the neurobiology of perception

The elephant-nosed electric fish

The elephant-nosed electric fish

By Olivia Zhu

Larry Abbott argues that sensation is not perception. In a lecture presented on March 25th to the Department of Neurobiology at Duke, Dr. Abbott, of the Center for Neurobiology and Behavior at Columbia University, presented his model of integrated perception.

Dr. Abbott went into particular depth about how an organism can tell itself apart from its surroundings. Though we may take it for granted, self-identification is extremely important in many instances: for example, when a young, male zebra finch learns how to sing by copying his tutor, he must be able to distinguish his own song from other birds’ songs in order to properly listen to it and refine it.

Dr. Abbott studies self-perception in elephant-nosed electric fish. Electric fish have an organ in their body that sends out strong electric pulses. However, the fish also have a sensory organ to detect electric pulses from potential prey, which are several orders of magnitude lower than their own signals. Their own electric fields should diminish their sensitivity to external electricity; this interference, though, is prevented because their electricity-generating organ sends impulses to the sensory organ to inform it when it is firing. Essentially, the fishes’ neural circuits are tuned to cancel out the input they receive from their own electric pulses.

Ultimately, Dr. Abbott claimed that when you look at your friend, you’re not exactly seeing your friend: your mental image is a product of various mental manipulations of the original sensory input your brain receives. His mathematical, model-based approach attempts to redefine the way in which we view ourselves and our relation to the world.

Jane Austen and Game Theory

game

Attendees played Regency Era card games involving game theory before the talk

By Olivia Zhu

“It is a great deal better to choose than to be chosen.” –Jane Austen, in Emma.

Jane Austen — novelist, romantic, and social critic — can now add another title to her repertoire: game theorist.

This role has been bestowed upon her by Michael Chwe, a game theorist in the Department of Political Science at UCLA and author of the book Jane Austen, Game Theorist. Chwe claims that Austen acts as a social scientist by setting up a theoretical framework for game theory in her novels. In his talk to a lively crowd well-versed in Austen’s works on March 25th, Chwe explained Austen’s uncanny emphasis on choice, preference, and strategic thinking.

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Chwe’s illustration of Jane’s choices and commensurability analysis in Pride and Prejudice

According to Chwe, Austen does not attribute actions to random variables, but rather to careful consideration of all alternatives. For example, Fanny Price in Mansfield Park chooses to refuse Henry Crawford’s offer of marriage after weighing her options; she does so entirely out of personal preference. Similarly, a major tenet in game theory is that the individual chooses what she wants to do without much consideration past her own wishes. Chwe said that Austen places a criticism on game theory here, when Fanny’s uncle, Sir Thomas, chastises Fanny being selfish instead of marrying Henry for the family’s financial security.

Chwe also introduced the game theory concept commensurability, in which negative factors are literally subtracted from positive factors in a decision to produce a single number of utility. He stated that Austen’s language, including phrases such as “finely checkered” happiness, “two

Chwe's playful histogram of Elizabeth Bennet's quantification of emotion.

Chwe’s playful histogram of Elizabeth Bennet’s quantification of emotion.

pleasures, however unlike in kind,” and “on the whole, no cause to repine,” clearly illustrate Austen’s intent to quantify emotions for commensurability.

Finally, Chwe pointed out the bounty of strategic thinking, another element of game theory, present in Austen’s novels. Austen does not portray calculation as unnatural or cold, he says. She mentions the word “scheme” 126 times, “contrive” 54 times, “foresight” 49 times, and “calculate” 41 times. Her strong, female characters often pride themselves on their ability to anticipate others’ actions.

Chwe concluded that though there is no direct evidence that Austen infused game theory into her novels, she clearly explores the concept of choice in her work.

Send in the Nerds

By Karl Leif Bates

Yeah, we're a bit excitable.

Yeah, we’re a bit excitable.

Hoping to triumph where our men’s and women’s basketball teams fell short, the Duke faculty are in the Final Four of an alternative NCAA bracket based on academic publications that’s being run by Thomson Reuters.

Sure, it’s a gimmick to get people looking at Thomson Reuters’ powerful but somewhat pricey InCites citation database  — but we’re winning!

By the reckoning of the “Metrics Mania” bracket, Duke is squaring off in the final with Stanford in a contest of “normalized citation impact” of our scholarly work. (It’s a weighted average of citations per paper that controls for year published and subject area.)

Joining us in the Final Four are Harvard and Wisconsin — kudos to the Badgers for making it both ways! We’ve apparently already beat Wisconsin on the normalized citation business, so now it’s on to the Cardinal.

Previous rounds had us clobbering Mercer (cough) and Iowa on absolute number of citations and then squeaking past Michigan and NC State on percentage of documents cited.

The national champion will be announced Tuesday, after the basketball game, Thomson Reuters’ savvy PR operation says.

*** UPDATE – Tuesday, April 8 ***

Stanford was declared the winner.  We’re done talking about this. :-(

Metrics Mania – Research Analytics – Thomson Reuters