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Who really hit the ball out of bounds?

April 24, 2019

ASU study finds self-centered bias in time perception of physical touch

The shot clock reads 0:05 in Game 7. Two players — one in yellow, the other red — hurtle towards the edge of the court, hands outstretched, chasing the ball. It sails out of bounds, and the play ends. Both players insist to the referee that the other touched the ball last. The crowd roars.

Deciding which player touched the ball last to determine possession is difficult because the event lasted only fractions of a second. But a wrong decision can impact the outcome of a game.

Players’ reactions in situations like this are often attributed to acting skills, even among professionals, but a team of Arizona State University psychologists wondered if both players might actually experience touching the ball first. In a paper published April 24 in Science Advances, the researchers tested how people interpret the timing and sequence of physical touches.

“When two players hit the ball out of bounds, there are frequently arguments between them about who touched it last,” said Ty Tang, an ASU psychology graduate student and first author on the study.

While it is possible that a player could lie in an effort to get the ball back, Tang and his graduate adviser Michael McBeath, professor of psychology, thought it could also be possible that both players really do experience hitting the ball first.

“With this clever study, Tang and McBeath zoom in on those moments that millions of sports fans look at every day,” said neuroscientist and New York Times best-selling author David Eagleman, who is an expert in time perception. “What would have previously been marked up to deceit or misjudgment has now been brought into the realm of basic neuroscience.”

What we perceive is not always reality

The research team created three tests to look at how people experience the order of perceptual events, like nearly simultaneous physical touches.

In the first experiment, two people sat across from each other at a table with a divider that prevented each participant from seeing the other. When a light flashed, the participants used their right index finger to quickly touch a sensor on the back of the other person’s left hand. Each participant then pushed a button to indicate whether they had touched the other person’s hand first or vice versa. The pair repeated this sequence 50 times, each time the light flashed. The light flashed at random times, and the participants were not told whether they were correct in their assessment of who had touched first.

When the touches happened at the same time both participants strongly believed they touched the other person earlier, answering 67% of the time that they were first.

“Even when the other person’s touch was 50 milliseconds earlier, it was still perceived to occur at the same time as one’s own touch,” Tang said.

The second experiment replaced one of the people with a mechanical device that tapped the participant’s hand. The third experiment had participants determine whether they touched first or a beep sounded first. These two follow-up experiments tested whether the presence of people was necessary and if the timing effects found in the first experiment generalized to other senses.

The results were the same: People always insisted they touched first. In the second and third experiments, there was again a 50-millisecond delay between the actual external touch or beep and when the participants felt it.

“The 50-millisecond time delay makes a lot of sense because we know the brain is always predicting our actions and perceptions” McBeath said. “People are generally accurate in the real-time perception of their own actions, like hitting and catching a baseball, but we need a little extra time to process something unplanned, like an unexpected tap on the shoulder. When something is unexpected, there is a slight perceptual delay while the brain figures it out.”

The findings from the study suggest the experience of an event a person initiates and one that happens to them are different. People seem to sequence these events in time by prioritizing their own action.

“Although we tend to think of time as something the brain passively tracks, in fact it is something the brain actively constructs. Studies like this demonstrate that our notion of when something happened is subjective — and is biased in clear, measurable ways,” Eagleman said.

This study was funded by Arizona State University and the Global Sports Initiative at ASU.

Top image: Two basketball players reach for the ball, knocking it out of bounds. ASU psychologists have found when physical touches happen at the same time, people actually experience they touched first. The research team also found a 50-millisecond delay between external and self-initiated events, with people experiencing external events as happening later. Photo by J and L Photography/Getty Images Sport/Getty Images

Science writer , Psychology Department

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Proofreading the book of life: Gene editing made safer

April 23, 2019

Making CRISPR 'immunosilent' is the next step toward safe clinical applications

The advance of science is something like an explorer wandering through an uncharted jungle. Often, the dense undergrowth can seem impenetrable, but at certain privileged moments, a clearing opens, and an entirely new landscape emerges.                                   

Something like this is occurring in the field of biology with the recent discovery of powerful techniques for intervening in the genetic code of life. A new method for editing genes with the ease of a computer’s cut-and-paste functions may prove more momentous than the splitting of the atom and represents a major advance in the war against deadly diseases.

The breakthrough — known as CRISPR — has been greeted both with ecstatic optimism and grave apprehension.

In research appearing in the advanced online edition of the journal Nature Communications, Karen Anderson, Samira Kiani and their colleagues at Arizona State University describe a method of rendering the gene editing tool CRISPR-Cas9 “immunosilent,” potentially allowing the editing and repair of genes to be accomplished reliably and stealthily.

The study is the first to accurately predict the dominant binding sites or epitopes responsible for immune recognition of the Cas9 protein and experimentally target them for modification. The findings bring CRISPR a step closer to safe clinical application.

Anderson is a professor in the Biodesign Virginia G. Piper Center for Personalized Diagnostics and ASU’s School of Life Sciences. She is also associate professor of medicine at Mayo Clinic Arizona. Kiani recently joined the Biodesign Institute in addition to her appointments at ASU’s School of Life Sciences and the School of Biological and Health Systems Engineering. Her research interests include the use of synthetic biology methods to improve CRISPR safety.

Karen Andersen

Karen Anderson is a professor in the Biodesign Virginia G. Piper Center for Personalized Diagnostics and ASU’s School of Life Sciences. 

Ancient tool, futuristic science

Back in 1987, a team of researchers in Osaka, Japan, found something peculiar. Identical genetic sequences appeared to be cropping up repeatedly in the bacterial genome of E. coli. These palindromic sequences were separated by abbreviated snippets of DNA of varying composition.

The nature of these strange repeated sequences and the curious DNA phrases separating them were an enigma. Remarkably, they started showing up in other bacteria. Indeed, the phenomenon seemed to be ubiquitous, and the race for an explanation was on.

Today we know that the researchers had stumbled on a previously unknown bacterial immune system — CRISPR (clustered regularly interspaced short palindromic repeats). 

CRISPR relies on two primary components. The first, known as a guide RNA, is a sort of molecular bloodhound, responsible for locating a particular site in the genome to be modified or disabled. The second component, known as Cas9, is a special type of protein known as an endonuclease. It functions like a pair of razor-sharp pruning shears, cutting through the double stranded DNA at the desired site located by the guide RNA. 

When a bacterium like E. coli is invaded by an unfamiliar virus — known as a bacteriophage — the CRISPR system is activated. If bacterial defense mechanisms successfully disable the virus, CRISPR chops the invader’s DNA into pieces and stores these fragments in a kind of genomic library. A subsequent viral assault on the bacterium will cause CRISPR to compare DNA segments of the offending virus with the bacterium’s data bank of DNA fragments from previous viral attacks. When the guide RNA finds a match along the virus’ DNA, it binds with the complementary sequence and the Cas9 protein severs the DNA, terminating the virus.

Nature 2.0

Clever researchers soon recognized the potential of CRISPR-Cas9 to serve as an all-purpose gene editing tool, useful not only for modifying selected regions throughout the entire bacterial genome, but the genomes of all living organisms, including humans. The possibilities are staggering and are not limited to effective treatments for a broad range of genetic diseases. For the first time, it may be possible to correct nature’s genetic typos, curing many of these diseases outright and preventing others from ever arising.

CRISPR also holds the potential to radically transform ecosystems and has been suggested as a means of wiping out diseases like malaria by driving the mosquitoes that carry them to extinction, through CRISPR-aided techniques known as gene drives.

For the first time in Earth’s history, one species holds the key to directing the course of its own evolution, (not to mention the evolution of bacteria, giraffes, redwood trees and all planetary life). Currently, there are prohibitions on gene editing efforts in humans that could be passed through the germline to successive generations, but in at least one case, these boundaries have been ominously overstepped. So powerful and versatile is the CRISPR method, there are likely few domains of applied biology that will remain untouched by it.

But before CRISPR can take its first tentative steps in the clinic, a number of safety issues must be addressed, beginning with the gene-slicing protein Cas9.

“Being as much a societal revolution as a technological revolution, many researchers have started to look into ethical, societal, safety and regulatory considerations related to CRISPR usage,” Kiani said. “Safety engineering to address controllability, specificity and side effects of CRISPR treatments have gained significant momentum and ethical debates have arisen to ensure correct use of technology. My lab is interested to address both issues.”

Samira Kiani

Samira Kiani recently joined the Biodesign Institute in addition to her appointments at ASU’s School of Life Sciences and the School of Biological and Health Systems Engineering. 

Managing immunity

Cas9 is a precise and versatile tool, replacing early, inaccurate and inefficient gene editing techniques with a rapid, inexpensive and deadly-accurate cutting device. But Cas9 in its native form may not be well tolerated by the human body.

Making CRISPR technology safe for clinical use is a central concern and the issue is challenging. One necessity is to ensure that the central machinery of CRISPR is not recognized by a patient’s immune system as a foreign entity and attacked. An immune response of this kind could cause significant toxicity. (An early, pre-CRISPR method of introducing altered genes to correct a rare genetic disorder resulted in tragedy when an immune system revolt caused multiple organ failure and death. Today, improved vectors for gene therapy have resulted in safer treatments for a range of genetic disorders, though "off-target" effects of these interventions remain an important concern.)

The Cas9 protein is derived from a common bacterium, streptococcus pyogenes. “The problem is that many of us are already immune to streptococcus," Anderson said. "If you have had a Group A strep infection, you may have preexisting immunity to that protein.”

S. pyogenes is a round bacterium that commonly colonizes the throat, genital mucosa, rectum and skin, affecting 700 million people annually worldwide. It is responsible for diseases ranging from rheumatic fever and rheumatic heart disease to scarlet fever and streptococcal pharyngitis — commonly known as strep throat.

In previous gene editing efforts, cells were removed from human tissue, reengineered and replaced in the body. The power of CRISPR allows researchers to modify DNA within a living person’s tissue and even to target multiple gene modifications with a single CRISPR intervention.

“If you want to think about repairing cells that are in an organ, like a liver cell or kidney or brain, then you have to express the bacterial protein there,” Anderson said.

This is where the threat of triggering an immune response to Cas9 becomes a formidable obstacle.  

Cas9 goes incognito

The new study affirms that Cas9 is indeed immunogenic in humans and that preexisting exposure to S. pyogenes can drive the body’s T cells to launch an immune attack against the bacterial protein. When 143 samples of blood were screened, 82 of them (or 57.3%) showed detectable levels of antibody to S. pyogenes.

The study next describes an effort to produce a fully functional version of Cas9, suitable for gene editing, which is not recognized and targeted by the immune system. To do this, the researchers identified the regions of antibody binding on the Cas9 molecule (known as epitopes) that were directly implicated in triggering T cell recognition and attack.

Two mutations in so-called anchor residues of the Cas9 epitope were explored individually and in combination to assess their effect on immunogenicity. Modifying these regions by just a single amino acid produced a version of Cas9 that could operate undercover. T-cell reactivity to the mutated peptide showed a 25-30 fold reduction, while leaving Cas9’s DNA-cutting ability intact.

“That’s the unique part of what we’ve done,” Anderson said. “We took those dominant epitopes and tried to silence them — just by doing one or two mutations in the Cas9 gene. But we rebuilt it, so the gene was still functional. It’s not immunologically silent, but it's more quiet.”

Indeed, the study results confirmed that in cultured cells, the reengineered Cas9 was less immunologically active, while retaining its functional properties. The authors stress that the technique could be combined with other strategies to further improve CRISPR safety and reduce the need for immunosuppressant drugs.

Exciting new avenues of research are being explored that would enable CRISPR to be used to induce epigenetic changes, turning on silent genes, altering the activity of disrupted genes or otherwise modifying gene expression without permanent changes to the DNA. Such interventions will require the CRISPR system to remain much longer in the body to be effective, perhaps weeks or months. Here, potential immunity to Cas9 will be even more of a critical consideration. Custom tailoring of epitopes to silence the immune response to Cas9 offers an attractive approach.

“We are hoping that this study is the beginning of many efforts that when combined can address the immunogenicity of CRISPR for clinical trials,” Kiani said.

More stories on the future of DNA

Top image: The graphic illustrates the technique described in the new study. A version of the Cas9 protein used in CRISPR gene editing has been mutated. While this protein, seen in blue, retains its proper functioning, it remains more "immunosilent"— hidden from predation as a foreign entity by the immune system's T cells (seen in brown). Graphic by Jason Drees

Richard Harth

Science writer , Biodesign Institute at ASU

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Anthropology meets genetics to tell our collective story

ASU Regents' Professor Anne Stone talks about the the latest research in DNA and where it’s going in the future


April 23, 2019

We know that our DNA can tell us a lot about ourselves, from susceptibility to certain cancer types to biological relationships. With services like 23andMe growing in popularity, it seems we are also increasingly interested in what our genes can tell us about our past.

“People enjoy learning more about where they came from, and these kits are one way to do that,” said Anne Stone, a Regents’ Professor in the School of Human Evolution and Social Change and a research affiliate with the Institute of Human Origins at Arizona State University.  photo of Stone in her lab Regents' Professor Anne Stone in her lab. Photo courtesy of ASU Now

But unlike mail-in kits that only give insight into the individual, Stone, an anthropological geneticist, sees DNA’s larger potential for societal and historical revelations.

At her ASU-based Laboratory of Molecular Anthropology, she and her students examine a wide range of topics, from the population history of Peru and the Caribbean, to the microbes that live in the mouths of chimpanzees, humans and other primates.

In 2016, her work in health and populations earned her a place in the prestigious National Academy of Sciences.

Below, she answers questions about the latest research in her field and where it’s going in the future.

Answers have been edited for length and clarity.

Question: What is anthropological genetics?

Answer: Basically, we are using genetic analyses to address questions related to human or primate population history, adaptation or even community relationships. This gives us further insight into human variation and our fascinating past.

Q: How is the field not just answering questions about the past, but also helping make our lives better today and tomorrow?

A: There are several different projects currently in my laboratory that my graduate students and postdocs are working on — genetics is a team effort! — which could have implications for the future.

For example, we are analyzing ancient DNA to learn about the evolutionary history of M. tuberculosis (the pathogen causing tuberculosis) before and after the “Age of Discovery/Colonization.”

This helps us see how the pathogen changes over time and in different hosts, which can help us understand how this pathogen evolves even as it jumps from one host to another. This can provide insight into better ways to design drugs that don’t evolve resistant pathogens. It could also help assess how much of a threat pathogens in other organisms might be.

Another project is testing new forensic methods to extract and analyze DNA from degraded bones, which may lead to new methods to improve our ability to identify victims of forest fires or other disasters.

Q: What are some of the opportunities you see for future research in the field?

A: I think that the biggest changes are likely to be in terms of improving bioinformatics methods to analyze genomic data, which will help us understand more about the complex demographic history of humans and how we have adapted to different environments.

The strength of an anthropological approach is the cross-cultural and interdisciplinary perspective that we typically have. I am always inspired by my students; former undergraduate and graduate students from my lab are now working on a range of interesting projects, including growing bone stem cell “organoids” to understand how bone cells work and influence morphological traits, studying adaptation in tropical hunter-gatherers and comparing how the microbiomes among rural and urban populations differ to see how this might influence health.

More stories on the future of DNA

Mikala Kass

Editorial Communications Coordinator, School of Human Evolution and Social Change

480-965-0610

 
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Chewing the fat: Understanding how we talk about our bodies

April 22, 2019

Cindi SturtzSreetharan was driving her daughter home from school when her daughter asked, “Do you think my thighs look fat?” The child was 9 years old.

Some moms would have found this interaction heart-wrenching and disconcerting. This was not the case for SturtzSreetharan. As a linguistic anthropologist at Arizona State University, she studies the ways people use language to construct culture and meaning. She knew that questions like, “Do I look fat?” are a common conversation engagement strategy called “fat talk.”

Her daughter could have picked it up anywhere. Here sat not an insecure fourth-grader, but a representation of a cultural norm.

SturtzSreetharan’s research in ASU’s Center for Global Health aims to understand how body weight influences our physical, emotional, cultural and social lives. Findings from her latest study were published in the Journal of Sociolinguistics on April 11.

Worries about bodies and weight affect people of every gender, race, class and age in the U.S. How people engage in fat talk and other conversations about weight could significantly impact how they respond and participate in their own social lives, neighborhoods and communities.

What is fat talk?

Fat talk is defined as self-deprecating talk about one’s body to others. Mimi Nichter, a sociocultural anthropologist from the University of Arizona, coined the term in the 1990s.

“Does this make me look fat?” shows up in conversation much like “How are you?” Both questions have a seemingly preprogrammed cultural response, in that there are set ways to respond that people just know. If someone asks you how you are, you are most likely to say, “Fine.” If someone asks whether an outfit makes them look fat, you are inclined to say “No,” regardless of what you are thinking.

SturtzSreetharan’s latest publication focuses on fat talk in Arizona, specifically the Tempe community. However, the research team also collected data from around the world, finding that fat talk exchanges occur throughout America and across the globe.

How — and how often — this exchange occurs without conscious thought is both fascinating and potentially alarming.

Line drawing of men in swim trunks

Line drawing of men with BMI 25 outside at a pool party in swim trunks. Line drawing courtesy of Cindi SturtzSreetharan

Words and culture

Culture and language are connected — they are in constant dialogue with one another. Linguistic anthropology is the study of the interactions, motivations and intentions associated with language and their effects on culture and society.

The field originated in North America, where many experts remain concentrated. Initially, linguistic anthropologists studied indigenous languages in the U.S. to highlight that studying a culture without knowing its language would yield a less accurate understanding of the human condition and human behavior.

“Linguistic anthropology is important because language is a resource humans have that they think that they completely understand and control,” SturtzSreetharan said. “They think they know what they’re doing. From my perspective, language is like a hot potato that is actually very difficult to control across receivers, across audiences and even across producers.”

Learning to appreciate the nuances of language can help inspire compassion, SturtzSreetharan said. These linguistic exchanges can allow us to dive deeper into culture and enhance our understanding of how humans interact.

Translating fat talk

SturtzSreetharan is the only linguistic anthropologist in ASU’s School of Human Evolution and Social Change. She was drawn to ASU by its interdisciplinary approach, which provides a unique space to discuss how we talk about weight and obesity, combining the perspectives of health science, linguistics and cultural studies.

“It struck me that the ways stigma is felt and expressed with regard to issues of weight and large bodies mimics the ways in which people feel and express stigma with regard to language,” she said.

ASU students work with the researchers, collecting and processing data from within the U.S. and abroad. Brian Suchowierski, an undergraduate student working on global fat talk, says he gained a new perspective.

“People often say that everyone shares insecurities across the board no matter who they are, what they are, how old they are, and I think (this research) kind of shines light on that. It might happen less frequently at certain ages, but everyone shares these same anxieties and issues, and they all talk about it in similar ways,” he says.

Hayley Trickey, another undergraduate student involved in the project, says she enjoyed working with community members. She says higher education can be inaccessible to some people. Going into the community and involving them in projects allows people to see what ASU brings to the state.

Line drawing of women in fitting room

The ASU research team asked women to fill in the speech balloons in a fitting-room conversation. Line drawing courtesy of Cindi SturtzSreetharan

Two women walk into a fitting room

The team began their research by surveying adult women in Arizona about a line drawing of women trying on bathing suits in a fitting room. The drawing used the Stunkard figuring scale, a scale of people's body sizes correlated to a body mass index (BMI).

The women were drawn to illustrate a BMI of 25. A doctor would encourage a patient at this BMI to remain the same weight, but not gain any more.

In the survey, there are speech bubbles for both women. The first says “Does this make me look fat?” and the other is blank to prompt the respondent to enter an answer. Then the same two women appear in a second frame, allowing for another interaction.

The most common response was, “You look fine.” If there was a negative response, it was commonly stated as “Maybe you should try a different color.” American women seemed to share an understanding that they were not supposed to say the other woman looked fat.

The researchers also surveyed men with a male line drawing and a similar prompt. They found that while denial was the most common response among women, advice and validation were more common among men.

They piloted this study in Arizona, then sent it to Japan, Korea, the United Kingdom, New Zealand, Guatemala, Iceland and Paraguay.

“What we learned by this was in some ways not surprising. We learned that the normative script overwhelmingly is to say, ‘No, you don’t look fat — you look fine’ or something like that everywhere around the world,” SturtzSreetharan said.

“It’s fascinating but also potentially concerning that fat talk is globalizing. There’s a lot of literature that suggests that fat talk is potentially psychologically damaging. But we really don’t know if that applies outside of the U.S.,” said Alexandra Brewis Slade, a President’s Professor in the School of Human Evolution and Social Change and a collaborator on the project.

She notes that the increasingly globalized fat talk seems to align with a growing lack of empathy toward large bodies and an expectation for everyone to look acceptably thin. She explains that the response to people asking if they look fat is automatically “no” because socially, the answer cannot be “yes” without being hurtful.

Most experts say that fat talk is bad because it lowers self-esteem and body satisfaction. But SturtzSreetharan believes that fat talk is more complicated than that.

“On some level that may be how we gain support and build our networks, and that may be how we make sure we feel comfort with the people we’re around. So, I think it's also this balance where these conversations don't necessarily have to be shut down, but the awareness that these kinds of conversations are everywhere is important,” she said.

Indeed, she and her colleagues find that in the U.S., people show keen sensitivity to the other speaker’s feelings when engaging in fat talk.

Understanding fat talk

The importance for SturtzSreetharan lies not in changing this cultural norm, but in understanding the interaction. 

SturtzSreetharan says if you don’t talk about baseball, the weather or politics, you can just talk about fat and bodies.

“On some level, I’m not rejecting the literature that finds that it can make somebody's body satisfaction plummet or decrease, but I also think that as an interaction, it may be doing a few other things. And that is what I think we're really interested in here — figuring out, what does this interaction do? And this isn’t just about fat per se, but we also do this with our aging bodies as well,” she said.

Ultimately, SturtzSreetharan simply doesn’t want her kids to have to think about their weight all of the time. She wants to instill ways to negotiate fat talk scenarios without sacrificing self-esteem or body satisfaction. She says she hopes to teach her daughters how to think through these conversations and join in without assigning guilt or shame.

Fat talk research was funded by the Virginia G. Piper Charitable Trust.

Written by Madison Arnold.

Top photo: Student research assistants code data for the “Fat talk: A citizen sociolinguistic approach” project. Photo by Cindi SturtzSreetharan

Using DNA templates to harness the sun’s energy


April 22, 2019

As the world struggles to meet the increasing demand for energy, coupled with the rising levels of CO2 in the atmosphere from deforestation and the use of fossil fuels, photosynthesis in nature simply cannot keep up with the carbon cycle. But what if we could help the natural carbon cycle by learning from photosynthesis to generate our own sources of energy that didn't generate CO2? Artificial photosynthesis does just that, harnessing the sun's energy to generate fuel in ways that minimize CO2 production.

In a recent paper published in the Journal of the American Chemical Society, a team of researchers led by Hao Yan, Yan Liu and Neal Woodbury of the School of Molecular Sciences and Biodesign Center for Molecular Design and Biomimetics at Arizona State University report significant progress in optimizing systems that mimic the first stage of photosynthesis, capturing and harnessing light energy from the sun. Double-stranded DNA acts as a template for self-assembly of cyanine dyes that serve as "exciton wires" for directional energy transport. Double-stranded DNA as a template to guide self-assembly of cyanine dye forming strongly-coupled dye aggregates. These DNA-templated dye aggregates serve as “exciton wires” to facilitate directional, efficient energy transfer over distances up to 32 nm. Download Full Image

Recalling what we learned in biology class, the first step in photosynthesis in a plant leaf is capture of light energy by chlorophyll molecules. The next step is efficiently transferring that light energy to the part of the photosynthetic reaction center where the light-powered chemistry takes place. This process, called energy transfer, occurs efficiently in natural photosynthesis in the antenna complex. Like the antenna of a radio or a television, the job of the photosynthetic antenna complex is to gather the absorbed light energy and funnel it to the right place. How can we build our own “energy transfer antenna complexes”, i.e., artificial structures that absorb light energy and transfer it over distance to where it can be used?  

“Photosynthesis has mastered the art of collecting light energy and moving it over substantial distances to the right place for light-driven chemistry to take place," Woodbury said. "The problem with the natural complexes is that they are hard to reproduce from a design perspective; we can use them as they are, but we want to create systems that serve our own purposes. By using some of the same tricks as nature, but in the context of a DNA structure that we can design precisely, we overcome this limitation, and enable the creation of light harvesting systems that efficiently transfer the energy of light where we want it.”

Yan’s lab has developed a way to use DNA to self-assemble structures that can serve as templates for assembling molecular complexes with almost unlimited control over size, shape and function. Using DNA architectures as a template, the researchers were able to aggregate dye molecules in structures that captured and transferred energy over tens of nanometers with an efficiency loss of less than 1% per nanometer. In this way the dye aggregates mimic the function of the chlorophyll-based antenna complex in natural photosynthesis by efficiently transferring light energy over long distances from the place where it is absorbed to the place where it will be used.

To further study biomimetic light harvesting complexes based on self-assembled dye-DNA nanostructures, Yan, Woodbury and Lin have received a grant from the Department of Energy. In previous work funded by the department, Yan and his team demonstrated the utility of DNA to serve as a programmable template for aggregating dyes. To build upon these findings, they will use the photonic principles that underlie natural light harvesting complexes to construct programmable structures based on DNA self-assembly, which provides the flexible platform necessary for the design and development of complex molecular photonic systems.

“It is great to see DNA can be programmed as a scaffolding template to mimic nature’s light harvesting antennae to transfer energy over this long distance,” Yan said. “This is a great demonstration of research outcome from a highly interdisciplinary team.”

The potential outcomes of this research could reveal new ways of capturing energy and transferring it over longer distances without net loss. In turn, the impact from this research could lead the way to designing more efficient energy conversion systems that will reduce our dependency on fossil fuels.

“I was delighted to participate in this research and to be able to build on some long-term work extended back to some very fruitful collaborations with scientists and engineers at Eastman Kodak and the University of Rochester,” said David G. Whitten of the University of New Mexico, Department of Chemical and Biological Engineering. “This research included using their cyanines to form aggregated assemblies where long range energy transfer between a donor cyanine aggregate and an acceptor occurs.”

The work reported in the Journal of the American Chemical Society was performed by ASU students Xu Zhou and Sarthak Mandal, now of the National Institute of Technology in Tiruchirappalli, India, and Su Lin of the Center for Innovations in Medicine at the Biodesign Institute, and Whitten’s student Jianzhong Yang in collaboration along with Yan and Woodbury.

The Department of Energy's Office of Science is the largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. 

Communication specialist, School of Molecular Sciences

ASU-led NASA Psyche Mission to offer free online courses to learn about space exploration


April 18, 2019

The NASA Psyche Mission is a journey to a unique metal world called Psyche, an asteroid orbiting the sun between Mars and Jupiter. The mission is currently in development and the spacecraft will launch in 2022. 

While instruments and components of the spacecraft are being designed and built across the country, the Psyche Mission management team, led by Arizona State University, is launching a series of free online courses called the NASA Psyche Mission Innovation Toolkit, based on the real-world challenges and skills associated with the Psyche mission’s science, engineering, technology, and teamwork. Artist's rendition of a space mission control room, part of the materials included in the NASA Psyche Mission Innovation Toolkit. Image courtesy ASU EdPlus Download Full Image

“Our purpose in space exploration is to inspire and connect with all of humankind,” said Psyche mission principal investigator Lindy Elkins-Tanton of ASU’s School of Earth and Space Exploration. “The Psyche Mission Innovation Toolkit allows anyone in the world with internet access to learn the process, the words and the ideas behind a mission. We want to inspire everyone to imagine and plan how they are designing and running their own mission, whether it's to space, or a way to improve their community or drive their own vision."

The first course offering, "The Process and Lifetime of a Space Mission," gives students the opportunity to follow the creation of a NASA robotic space mission, from preparation and submission of a proposal, to team-building, design, construction, modeling, testing, launching, tracking and data collection and analysis.

“A space mission encompasses so much more than reaching a destination and sending back discoveries,” said Psyche mission co-investigator Cassie Bowman, who leads the mission’s online course program. “This first course being offered by the Psyche mission gives students the opportunity to learn about, and practice, elements of the process and lifetime of a space mission, from idea to flight.”

The course is divided into five modules that take approximately one hour to complete. During the course, enrolled learners can create their own online portfolio — called an "ePortfolio" — of their work and reflections. Participants who complete the course receive a downloadable and printable certificate of completion.

"The Process and Lifetime of a Space Mission" course is available to anyone online for free on ASU’s Continuing and Professional Education website. The only prerequisite is an interest in space exploration and the behind-the-scenes work that goes into planning and conducting a space mission. It is also recommended that participants have a persistent internet connection and the ability to read, write, and understand English or use a language translation program.

The Psyche mission team has plans to offer several more courses over the life of the mission and is currently working on a second course on this same platform, titled "The Inclusive Mindset: Tools for Building Positive Team Culture." The course is being developed in collaboration with Mansour Javidan, the Garvin Distinguished Professor of Management at ASU’s Thunderbird School of Global Management and director of the Najafi Global Mindset Institute.

This second course, which will be available later this year, will help learners understand the unique challenges and opportunities facing diverse teams; and to develop a set of skills to become more successful as leaders and team members.

“Every endeavor is a human endeavor and going to space is truly about the team,” Elkins-Tanton said. “So, for a successful mission, we want to build the very best teams and we are so fortunate to have one of the world's experts on teams, Mansour Javidan, help us design and build this course."

The Psyche mission

Psyche, an asteroid orbiting the sun between Mars and Jupiter, is made almost entirely of nickel-iron metal. As such, it offers a unique look into the violent collisions that created Earth and the terrestrial planets.

The Psyche spacecraft is planned to launch in August 2022 and travel to the asteroid using solar-electric (low thrust) propulsion. After flying by Mars in 2023 for a gravity assist, the spacecraft will arrive at Psyche in 2026 and spend 21 months orbiting the asteroid, mapping it and studying its properties.

The scientific goals of the Psyche mission are to understand the building blocks of planet formation and explore firsthand a wholly new and unexplored type of world. The mission team seeks to determine whether Psyche is the core of an early planet, how old it is, whether it formed in similar ways to the Earth's core, and what its surface is like.

The spacecraft's instrument payload will include a magnetometer, a multispectral imager, and a gamma ray and neutron spectrometer. The mission will also test a sophisticated new laser communications technology, called Deep Space Optical Communications.

The Psyche Mission is part of NASA's Discovery Program. Psyche Principal Investigator, Lindy Elkins-Tanton, is the director of ASU’s School of Earth and Space Exploration. Other ASU researchers on the Psyche mission team include Jim Bell (deputy principal investigator and co-investigator), David Williams (co-investigator), and Catherine Bowman (co-investigator and student collaborations lead).

The mission is led by Arizona State University. NASA’s Jet Propulsion Laboratory is responsible for the mission’s overall management, system engineering, integration and test, and mission operations. Maxar Space Solutions, formerly Space Systems Loral, is providing a high-power solar electric propulsion spacecraft chassis.

Karin Valentine

Media Relations & Marketing manager, School of Earth and Space Exploration

480-965-9345

Epigenetic study reveals potential for earlier diagnosis in Parkinson’s disease


April 17, 2019

Parkinson’s disease, a neurodegenerative disorder, largely affects movement and causes irreversible neuronal damage. It may start with a tremor or it may be manifested in a speech problem; however, by the time symptoms are evident, it is too late to halt the course of the disease. 

Parkinson's originates from the loss of neurons releasing dopamine. Because these neurons control coordination in movement, their loss results in a multitude of movement-related deficiencies. PD Parkinson's disease originates from the loss of neurons releasing dopamine. Because these neurons control coordination in movement, their loss results in a multitude of movement-related deficiencies. Download Full Image

Although there is medication to treat the symptoms of Parkinson's, there is no known cure. To mediate this problem and propose more effective therapeutic strategies, an earlier diagnosis is key.

“One of the biggest issues with neurodegenerative diseases like Parkinson’s disease or Alzheimer’s disease is that diagnosis is mostly clinically based, and it comes late in the disease — the brain is already degenerated, and it is extremely difficult to restore brain function at that stage,” said Travis Dunckley, an assistant research professor at the ASU-Banner Neurodegenerative Disease Research Center and the School of Life Sciences.

Dunckley teamed up with other universities including UCSD, Texas A&M and Harvard University and research institutes such as TGen to study the epigenetic changes in Parkinson's patients over time, specifically alterations in DNA methylation patterns over the course of the disease. If researchers were to obtain a better understanding of the DNA methylome in Parkinson's patients, they could potentially diagnose the disease earlier.

Currently, the disease is identified through clinical symptoms related to physical movement.

“When physicians treat PD patients, it is usually too late to change the trajectory of the disease. I am interested in early diagnostics to try to identify people prone to the disease before they get it,” Dunckley added. “Using this approach, you could put patients at risk for PD on certain therapies before symptoms arise.”

Parkinson's is governed both by genetic factors and environmental factors, making epigenetics an apt area of study.

“It’s about 60% environmental — it’s much less genetic than many other neurodegenerative diseases,” Dunckley said. “It’s made of up of environmental interactions with the genome. One of the major ways that the environment acts with the genome is through epigenetics.”

DNA methylation, one form of epigenetic alteration of genes, is a process during which methyl groups are added to DNA. These methyl groups can change the activity of the DNA without changing its sequence. However, in the context of Parkinson's disease, it can be difficult to conclude that changes in DNA methylation are solely correlated to disease progression.

“It is hard to link them without confounding variables in that there are a lot of environmental factors,” Dunckley said. “It’s difficult to say whether epigenetic changes are based on disease, environmental factors or a combination of disease and environmental factors.”

In this study, the largest longitudinal epigenetic study in Parkinson's disease to date, 189 patients’ methylomes were studied and compared to that of 191 control subjects. Two years later, their methylomes were compared once again.

The project identified distinct methylation patterns in Parkinson's patients relative to control patients and identified specific sites at which methylation changed longitudinally. The study also found differences in methylation patterns for those subjected to anti-Parkinson’s drugs (dopamine replacement drugs) versus those who received no treatment. The researchers found that DNA methylation changed more for those patients without treatment, further exacerbating the link between epigenetics and Parkinson's progression.

“The main findings are that one, the epigenome does change as the disease progresses. The second finding is that the PD medications themselves alter the epigenome,” Dunckley added. 

If researchers can identify changes in methylation that are characteristic of Parkinson's disease, they can diagnose earlier, allowing for more effective therapeutic strategies before there is irreversible damage. The methylation signatures are therefore promising candidates for biomarkers useful in early detection. 

To expand the scope of the project, Dunckley and his counterparts are repeating the same study but with a longer range of time and with a new subset of patients. 

“The next study we are doing is a replication and extension of this one to validate the findings and extend the observation period to five years,” Dunckley said. “We are also including patients that are very early in PD progression, patients who have symptoms that are highly predictive of future PD. The ultimate goal is to identify changes in these earliest stages of disease that can be predictive of future PD onset.”

Further exploration of epigenetic changes like DNA methylation promise to expand the understanding of this enigmatic disease and hopefully point the way to effective treatments.

Gabrielle Hirneise

Assistant science writer , Biodesign Institute

480-433-4272

 
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The history of humanity is in your face

April 15, 2019

Changes in the shape of human faces over time reveals the evolution of how we eat, breathe and communicate

The face you see in the mirror is the result of millions of years of evolution and reflects the most distinctive features that we use to identify and recognize each other, molded by our need to eat, breathe, see and communicate.

But how did the modern human face evolve to look the way it does? Eight of the top experts on the evolution of the human face, including Arizona State University’s William Kimbel, collaborated on an article published this week in the journal Nature Ecology and Evolution to tell this 4 million-year-old story. Kimbel is the director of the Institute of Human Origins and Virginia M. Ullman Professor of Natural History and the Environment in the School of Human Evolution and Social Change.

After our ancestors stood on two legs and began to walk upright, at least 4.5 million years ago, the skeletal framework of a bipedal creature was pretty well formed. Limbs and digits became longer or shorter, but the functional architecture of bipedal locomotion had developed.

But the skull and teeth provide a rich library of changes that we can track over time, describing the history of evolution of our species. Prime factors in the changing structure of the face include a growing brain and adaptations to respiratory and energy demands. But most importantly, changes in the jaw, teeth and face responded to shifts in diet and feeding behavior. We are, or we evolved to be, what we eat — literally!

Diet has played a large role in explaining evolutionary changes in facial shape. The earliest human ancestors ate tough plant foods that required large jaw muscles and cheek teeth to break down, and their faces were correspondingly broad and deep, with massive muscle attachment areas.

As the environment changed to drier, less wooded conditions, especially in the last 2 million years, early Homo species began to routinely use tools to break down foods or cut meat. The jaws and teeth changed to meet a less demanding food source, and the face became more delicate, with a flatter countenance.

Changes in the human face may not be due only to purely mechanical factors. The human face, after all, plays an important role in social interaction, emotion and communication. Some of these changes may be driven, in part, by social context. Our ancestors were challenged by the environment and increasingly impacted by culture and social factors. Over time, the ability to form diverse facial expressions likely enhanced nonverbal communication.

Large, protruding brow ridges are typical of some extinct species of our own genus, Homo, like Homo erectus and the Neanderthals. What function did these structures play in adaptive changes in the face? The African great apes also have strong brow ridges, which researchers suggest help to communicate dominance or aggression. It is probably safe to conclude that similar social functions influenced the facial form of our ancestors and extinct relatives. Along with large, sharp canine teeth, large brow ridges were lost along the evolutionary road to our own species, perhaps as we evolved to become less aggressive and more cooperative in social contexts.

“We are a product of our past,” Kimbel said. “Understanding the process by which we became human entitles us to look at our own anatomy with wonder and to ask what different parts of our anatomy tell us about the historical pathway to modernity.”

Julie Russ

Assistant director , Institute of Human Origins

480-727-6571

 
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Team finds tiny fragment of a comet inside a meteorite

April 15, 2019

ASU researcher part of Carnegie Institution for Science-led team; discovery could shed light on early solar system's chemistry

A tiny piece of the building blocks from which comets formed has been discovered inside a primitive meteorite. The discovery by a Carnegie Institution for Science-led team, including a researcher now at Arizona State University, was published April 15 in Nature Astronomy.

The finding could offer clues to the formation, structure and evolution of the solar system.

"The meteorite is named LaPaz Icefield 02342," said research scientist Jemma Davidson, of ASU's Center for Meteorite Studies in the School of Earth and Space Exploration. "The name comes from where it was found in Antarctica's LaPaz Icefield."

She adds that it belongs to a class of primitive carbonaceous chondrite meteorites that have undergone minimal changes since they formed more than 4.5 billion years ago, likely beyond the orbit of Jupiter.

Construction debris

Meteorites were once part of larger bodies, asteroids, which broke up due to collisions in space and then survived the trip through Earth’s atmosphere. Their makeup can vary substantially from one meteorite to the next, reflecting their origins in diverse parent bodies that formed in different parts of the solar system.

Asteroids and comets both formed from the disk of gas and dust that once surrounded the young sun, but they aggregated at different distances from it, which affected their chemical makeup. Compared to asteroids, comets contain larger fractions of water ice and far more carbon, and typically formed farther from the sun where the environment was colder.

By studying a meteorite’s chemistry and mineralogy, researchers such as the paper’s lead author, Carnegie’s Larry Nittler, can unlock details about its formation and how much heating and other chemical processing it experienced during the solar system’s formative years. 

'Bonbon' with a surprise inside

Inside the LaPaz meteorite, Nittler’s team found a very carbon-rich slice of primitive material. It bears some striking similarities to extraterrestrial dust particles that are thought to have originated in comets that formed near the solar system’s outer edges. 

Approximately 3 million to 3.5 million years after the solar system formed, but while Earth was still growing, this tiny object — about one-tenth of a millimeter across — was captured by the growing asteroid from which the meteorite originated.

"Primitive meteorites provide a snapshot of the early solar system that we can study in the lab,” Davidson said. "The LaPaz meteorite is a nice example since it has experienced minimal terrestrial weathering."

Meteorites like LaPaz, she notes, are great places to hunt for presolar grains, microscopic pieces of stardust formed by stars that predate the solar system. But none of the team expected also to find evidence for a surviving cometary building block inside a meteorite.

Ancient survivor

"When I saw the first electron images of the carbon-rich material," Davidson said, "I knew we were looking at something very rare. It was one of those exciting moments you live for as a scientist."

By undertaking sophisticated chemical and isotopic analysis of the material, Nittler and his colleagues — who besides Davidson include Carnegie’s Conel Alexander as well as Rhonda Stroud and Bradley De Gregorio of the U.S. Naval Research Laboratory, and Josep Trigo-Rodríguez, Carles Moyano-Cambero and Safoura Tanbakouei of the Institute of Space Sciences in Barcelona, Catalonia — were able to show that the encased material likely originated in the icy outer solar system along with objects from the Kuiper Belt, where many comets originate. 

"Because this sample of cometary building-block material was swallowed by an asteroid and preserved inside this meteorite, it was protected from the ravages of entering Earth’s atmosphere," Nittler explained. "It gave us a peek at material that would not have survived to reach our planet’s surface on its own, helping us to understand the early solar system's chemistry."

The existence of this primitive material captured inside the meteorite suggests that due to the drag caused by the surrounding gas, particles like it migrated from the outer edges of the solar system, where comets and Kuiper Belt objects formed, to the closer-in area beyond Jupiter, where the carbonaceous chondrites formed. This reveals details about how our solar system’s architecture took shape during the early stages of planet formation. 

"Discoveries like this demonstrate how important it is to retrieve precious meteorites like LaPaz from Antarctica," Davidson said. "We never know what secrets they’ll reveal."

Top image: LaPaz Icefield 02342, named for where it was found in Antarctica, is a primitive meteorite of a type that formed at the dawn of solar system history. However, this particular meteorite (seen here in thin section by polarized light) contained a scientific surprise: a carbon-rich fragment of a cometary building block. Image by Carles Moyano-Cambero/Institute of Space Sciences, Barcelona

Robert Burnham

Science writer , School of Earth and Space Exploration

480-458-8207

 
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New techniques may detect CTE in brains of living former NFL players

April 10, 2019

When you search online for “CTE and NFL,” you’ll find a list of 54 professional football players who have died and were diagnosed with the degenerative brain disease chronic traumatic encephalopathy, or CTE — names like Frank Gifford, Ken Stabler, Bubba Smith and Andre Waters. It’s a smart guess that hundreds more are unaccounted for.

Next, you’ll see a list of living ex-NFL players including Brett Favre, Bernie Kosar and Jim McMahon, who have been diagnosed with “likely CTE.” And therein lies the problem: CTE cannot be detected until autopsy, leaving questions about who has it, when they get it, and how it affects their lives. To confirm CTE, scientists must rely on players and families who agree to donate their brains to research.  

But now, Arizona researchers are playing a key role in the search for new ways to identify CTE before death. In a study released online in the New England Journal of Medicine, a cross-national team, including local researchers from Arizona State University, Banner Alzheimer’s Institute, Mayo Clinic College of Medicine and Boston University have brought us a step closer to diagnosing CTE in living former NFL players.

The study demonstrates that an experimental positron emission tomography (PET) scan can detect a hallmark of CTE, the accumulation of abnormal tau protein in brain regions of living former NFL players who have cognitive, mood and behavior symptoms. The researchers also found that the more years of tackle football played (across all levels of play), the higher the tau protein levels detected by the PET scan.

Corresponding author Robert Stern, a professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine (BUSM), said that “the results of this study provide initial support for the flortaucipir PET scan to detect abnormal tau from CTE during life. However, we’re not there yet,” he cautioned. “These results do not mean that we can now diagnose CTE during life or that this experimental test is ready for use in the clinic.”

CTE is a neurodegenerative disease associated with repeated blows to the head. Symptoms of CTE can begin in a patient’s late 20s or early 30s. Common behaviors are anger, lack of impulse control, depression, suicidal thinking and paranoia. This is a brain disease for which there is no treatment.

In CTE, a protein called tau forms clumps that slowly spread through the brain, killing brain cells, and patients typically show a relative lack of the amyloid plaques which are associated with Alzheimer’s disease.

Diego Mastroeni, a researcher with the ASU-Banner Neurological Disease Research Center at the Biodesign Institute, first got an “up-close-and-personal” look when a member of Mastroeni’s family shared his concerns about memory issues and how his NFL career may have affected his brain. Mastroeni was recruited to speak at a meeting of Arizona’s NFL Alumni Association.

ASU researcher

Diego Mastroeni

“This was 2015. The NFL concussion settlement was in full form, but players needed to be diagnosed with dementia or mild cognitive impairment in order to qualify,” said Mastroeni. “By this time I was having personal communication with well over 50 retired NFL players. They were calling and emailing me daily, pleading for help, asking what to do.”

Methods for diagnosing CTE in living patients were undependable and expensive. A single brain scan cost about $10,000 at the time.

“When I say this is a vulnerable population, I mean it,” said Mastroeni. “It got to the point that I needed to find a way to help these guys at no cost to them.”

From his work with Alzheimer’s, Mastroeni knew that chances were good that CTE was brewing in the brain before symptoms began appearing.  

“Unfortunately, efforts to develop a diagnostic tool during life have largely been unsuccessful,” said Mastroeni. But Mastroeni also knew that advances in brain imaging techniques like PET scans were revolutionizing the field, providing a means to reliably detect and track brain changes in living subjects before the onset of memory loss in neurological conditions like Alzheimer’s disease. 

Mastroeni reached out to Marwan Sabbagh, a neuroscientist, formerly with Banner Alzheimer’s Institute and now with the Cleveland Clinic, and asked if he’d be willing to meet with Mastroeni’s relative and others who had expressed interest.

Next, Mastroeni connected with Eric Reiman, a leader in neuro-imaging, University Professor of Neurology at Arizona State University and executive director of Banner Alzheimer’s Institute, who knew just the right people with whom to partner.

“A couple weeks later, Bob Stern flew out from Boston and we hashed out a plan to image all the guys we could; some at BUSM, some at Banner and some at Mayo, at no cost to them,” said Mastroeni. Stern leads a CTE Center at BUSM where he is working to develop accurate methods to detect and diagnose CTE while the player is still alive, gaining a better understanding of risk factors for the disease — and understanding why some players get it and some do not.

WATCH: The race to create the safest football helmet

In 2014, Mastroeni sent a letter to NFL players who lived in Arizona, offering them the opportunity to be part of a study. After several appearances at the local NFL alumni chapter, some 60 players were eager to participate. Some of the patients were included in the study, and others did not meet the inclusion criteria. The state of Arizona provided enough funding to launch the study in Arizona, while researchers in Boston also recruited participants and secured their own funding.

The Arizona force was strong, involving not only Mastroeni and Reiman’s team in Arizona, but also neurologists David Dodick and Charles Adler at Mayo Clinic College of Medicine in Phoenix. The multidisciplinary group of researchers also included Brigham and Women’s Hospital and Avid Radiopharmaceuticals.

In the study, experimental flortaucipir PET scans (flortaucipir is the chemical used to measure tau in the PET scans) were used to assess tau deposition, and FDA-approved florbetapir PET scans were used to assess amyloid plaque deposition in the brains of 26 living former NFL players with cognitive, mood and behavioral symptoms (ages 40-69). There was also a control group of 31 same-aged men without symptoms or history of traumatic brain injury.

Results showed that the tau PET levels were significantly higher in the former NFL group than in the controls, and tau was seen in the specific areas of the brain that have been shown to be affected in post-mortem cases of neuropathologically diagnosed CTE.

Interestingly, the former player and control groups did not differ in their amyloid PET measurements. Indeed, only one former player had amyloid PET measurements comparable to those seen in Alzheimer’s disease (AD).

“Our findings suggest that mild cognitive, emotional and behavioral symptoms observed in athletes with a history of repetitive impacts are not attributable to AD, and they provide a foundation for additional research studies to advance the scientific understanding, diagnosis, treatment and prevention of CTE in living persons,” said co-author Reiman. “More research is needed to draw firm conclusions, and contact sports athletes, their families and other stakeholders are waiting."

With support from NIH, the authors are working with additional researchers to conduct a longitudinal study called the DIAGNOSE CTE Research Project in former NFL players, former college football players and persons without a history of contact sports play to help address these and other important questions. Initial results of that study are expected in early 2020.

Funding for this study was provided by grants from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company), the National Institutes of Health (grant numbers R01NS078337, U19AG024904, 1UL1TR001430); the state of Arizona; and the U.S. Department of Defense (grant numbers W81XWH-13-2-0063, W81XWH-13-2-0064, W81XWH-14-1-0462). All flortaucipir and florbetapir PET radiotracers were provided by Avid Radiopharmaceuticals.

Top image: CTE is a neurodegenerative disease associated with repeated blows to the head for which there is no treatment. Common behaviors include anger, lack of impulse control, depression, suicidal thinking and paranoia. 

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