The discovery of a signaling pathway in the brain that could make mice into ‘superlearners’ understandably touched off a lot of excitement a few years back.
But new work led by Duke neurologist and neuroscientist Nicole Calakos MD PhD suggests there’s more to the story of the superlearner chemical pathway than anybody realized.
A genetically-enhanced ‘smart mouse’ doing some important work. (Boston University)
In a study led by postdoctoral researchers Ashley Helseth and Ricardo Hernandez-Martinez, the Calakos lab developed a new tool to visualize activity of this Integrated Stress Response (ISR) signaling pathway because it contributes to synaptic plasticity – the brain’s ability to rewire circuits – as well as to learning and memory.
What they didn’t expect to see is that a population of cells called cholinergic interneurons, which comprise only 1 or 2 percent of the whole basal ganglia structure, seem to have the ISR pathway working all the time. The basal ganglia, which is the focus of much of Calakos’ work, plays a role in Parkinson’s and Huntington’s diseases, Tourette’s syndrome, obsessive compulsive disorder and more.
Nicole Calakos, the Lincoln Financial Group distinguished professor of Neurobiology and Neurology. (Alex Boerner)
“This totally changes how you think about the pathway,” Calakos said. “Everybody thought this pathway used an on-demand response type of mechanism, but what if some cells needed it for their everyday activities?”
To answer this, they blocked the ISR in just those rare interneurons in mice and it actually reproduced the enhanced performance on learned tasks that the earlier studies had shown when the pathway was blocked universally throughout the brain. This finding focuses attention on this select subset of brain cells, the cholinergic interneurons that release the chemical signal acetylcholine, as being responsible for at least some of the ‘superlearner’ behavior.
Since the integrated stress response pathway and its potential to enhance learning and memory was identified, drugs for dementia and traumatic brain injury are being designed to manipulate it and help the brain recover. But there may be more to the story than anyone realized, Calakos said.
“Our results show that the ISR plays a major role in acetylcholine-releasing cells, and our current best dementia drugs boost acetylcholine,” she said.
With their new tool, SPOTlight, the team were able to highlight the presence of cholinergic interneurons (red) which are only 1 to 2 percent of the cell population in the ganglia. (Helseth et al)
Acetylcholine, the chemical that these rare cholinergic interneurons use to signal in the brain, is well known for its powerful effects on influencing brain states for attention and learning. This finding suggests that at least some of the ‘superlearner’ properties of inhibiting the ISR occur by influencing brain state, rather than acting directly in the cells that are being rewired during learning.
In addition to the full research article, Science published on April 23 an article summary by Helseth and Calakos and a perspective piece by a pair of University of Minnesota neuroscientists highlighting the finding’s importance.
More work is required to sort out what ISR is and is not doing, but it’s possible that these new findings can help to develop “more precise, more nuanced Alzheimer’s drugs,” Calakos said.
Herman Pontzer explains where our calories really go, and what studying humanity’s past can teach us about staying healthy today.
Photo by Elena Georgiou, My City /EEA
Duke professor Herman Pontzer has spent his career counting calories. Not because he’s watching his waistline, exactly. But because, as he sees it, “in the economics of life, calories are the currency.” Every minute, everything the body does — growing, moving, fighting infection, even just existing — “all of it takes energy,” Pontzer says.
In his new book, “Burn,” the evolutionary anthropologist recounts the 10-plus years he and his colleagues have spent measuring the metabolisms of people ranging from ultra-athletes to office workers, as well as those of our closest animal relatives, and some of the surprising insights the research has revealed along the way.
Much of his work takes him to Tanzania, where members of the Hadza tribe still get their food the way our ancestors did — by hunting and gathering. By setting out on foot each day to hunt zebra and antelope or forage for berries and tubers, without guns or electricity or domesticated animals to lighten the load, the Hadza get more physical activity each day than most Westerners get in a week.
So they must burn more calories, right? Wrong.
Herman Pontzer, associate professor of evolutionary anthropology at Duke
Pontzer and his colleagues have found that, despite their high activity levels, the Hadza don’t burn more energy per day than sedentary people in the U.S. and Europe.
These and other recent findings are changing the way we understand the links between energy expenditure, exercise and diet. For example, we’ve all been told that if we want to burn more calories and fight fat, we need to work out to boost our metabolism. But Pontzer says it’s not so simple.
“Our metabolic engines were not crafted by millions of years of evolution to guarantee a beach-ready bikini body,” Pontzer says. But rather, our metabolism has been primed “to pack on more fat than any other ape.” What’s more, our metabolism responds to changes in exercise and diet in ways that thwart our efforts to shed pounds.
What this means, Pontzer says, is you can walk 16,000 steps each day like the Hadza and you won’t lose weight. Sure, if you run a marathon tomorrow you’ll burn more energy than you did today. But over time, metabolism responds to changes in activity to keep the total energy you spend in check.
Pontzer’s book is more than a romp through the Krebs cycle. For anyone suffering pandemic-induced pangs of frustrated wanderlust, it’s also filled with adventure. He takes readers on an hours-long trek to watch a Hadza man track a wounded giraffe across the savannah, to the rainforests of Uganda to study climbing chimpanzees, and to the foothills of the Caucasus Mountains to unearth the 1.8 million-year-old remains of some of the first people who trekked out of Africa.
His humor shines through along the way. Even when awoken by a chorus of 300-pound lions just a few hundred yards from his tent, he stops to ponder whether his own stench gives him away, and what he might do if they come for his “soft American carcass, the warm triple crème brie of human flesh.”
Pontzer spoke via email with Duke Today about his book:
Q: What’s the lesson the Hadza and other hunter-gatherers teach us about managing weight and staying healthy?
A: The Hadza stay incredibly fit and healthy throughout their lives, even into their older ages (60’s, 70’s, even 80’s). They don’t develop heart disease, diabetes, obesity, or the other diseases that we in the industrialized world are most likely to suffer from. They also have an incredibly active lifestyle, getting more physical activity in a typical day than most Americans get in a week.
My work with the Hadza showed that, surprisingly, even though they are so physically active, Hadza men and women burn the same number of calories each day as men and women in the U.S. and other industrialized countries. Instead of increasing the calories burned per day, the Hadza physical activity was changing the way they spend their calories — more on activity, less on other, unseen tasks in the body.
The takeaway for us here in the industrialized world is that we need to stay active to stay healthy, but we can’t count on exercise to increase our daily calorie burn. Our bodies adjust, keeping energy expenditure in a narrow range regardless of lifestyle. And that means that we need to focus on diet and the calories we consume in order to manage our weight. At the end of the day, our weight is a matter of calories eaten versus calories burned — and it’s really hard to change the calories we burn!
Q: You’re saying that exercise doesn’t matter? What’s the point, if we can’t eat that donut?
A: All those adjustments our bodies make responding to exercise are really important for our health! When we burn more calories on exercise, our bodies spend less energy on inflammation, stress reactivity (like cortisol), and other things that make us sick.
Q: What’s the biggest misunderstanding about human metabolism?
A: We’re told — through fitness magazines, diet fads, online calorie counters — that the energy we burn each day is under our control: if we exercise more, we’ll burn more calories and burn off fat. It’s not that simple! Your body is a clever, dynamic product of evolution, shifting and adapting to changes in our lifestyle.
Q: In your book you say we’re driven to magical thinking when it comes to calories. What do you mean by that?
A: Because our body is so clever and dynamic, and because humans are just bad at keeping track of what we eat, it’s awfully hard to keep track of the calories we consume and burn each day. That, along with the proliferation of fad diets and get-thin-quick schemes, has led to this idea that “calories don’t matter.” That’s magical thinking. Every ounce of your body — including every calorie of fat you carry — is food you consumed and didn’t burn off. If we want to lose weight, we must eat fewer calories than we burn. It really comes down to that.
Q: Some people say that if the cavemen didn’t eat it, we shouldn’t either. What does research show about what foods are “natural” for humans to eat?
A: There’s no singular, natural human diet. Hunter-gatherers like the Hadza eat a diverse mix of plant and animal foods that varies day to day, month to month, and year to year. There’s even more dietary diversity when we look across populations. Humans are built to thrive on a wide variety of diets — just about everything is on the menu.
That said, the ultra-processed foods we’re inundated with in our modern industrialized world really are unnatural. There are no Twinkies to forage in the wild. Those foods are literally engineered to be overconsumed, with a mix of flavors that overwhelm our brain’s ability to regulate our appetites. Now, it is still possible to lose weight on a Twinkie diet (I’m not recommending it!), if you’re very strict about the calories eaten per day. But we need to be really careful about how we incorporate ultra-processed foods into our daily diets, because they are calorie bombs that drive us to overconsume.
Q: If we could time travel, what would our hunter-gatherer ancestors make of our industrialized diet today?
A: We don’t even need to imagine — We are those hunter-gatherers! Biologically, genetically, we are the same species that we were a hundred thousand years ago, when hunting and gathering were the only game in town. When we’re confronted with modern ultra-processed foods, we struggle. They are engineered to be delicious, and we tend to overconsume.
Q: Has the COVID-19 pandemic brought any of these lessons home for you? What can we do to keep active and watch what we eat, even while working from home?
The pandemic has been a tragedy on so many levels — the loss of life, those suffering with long-term effects, the social and economic impacts. The impact on diet and exercise have been bad as well, for many of us. Stress eating is a real phenomenon, and the stress and emotional toll of the pandemic — along with having easy access to the snacks in our kitchen — have led many to gain weight. Physical activity seems to have declined for many. There aren’t easy answers, but we should try to make a point to get active every day. And we can help ourselves make better decisions about food by keeping ultra-processed foods out of our houses. You can’t plow through a bag of chips if you don’t have chips in your cupboard.
Q: You’ve measured the energy costs of activities ranging from taking a breath to doing an Ironman. What is one of the more extreme or surprising calorie-burning activities that you’ve measured, or would like to measure, in humans or some other animal?
A: With colleagues from Japan, I measured the energy cost of a heartbeat – a tricky bit of metabolic measurement! Turns out each beat of your heart burns about 1/300th of a kilocalorie! Amazing how efficient our bodies can be.
Q: What is something people have questions about that we just don’t know the answer to yet? What would it take to find out?
A: Right now we’re excited about measuring the adjustments our bodies make when we increase our exercise: how exactly does burning more energy on physical activity impact our immune system, our stress response, our reproductive system? It will take a long-term study of exercise to see how these systems change over time.
One morning in November, during a visit to my parents’ house in Richmond, Virginia, I woke up to a text from my mom. “Evening Grosbeaks at the river. Want to go?” Obviously I wanted to go. I’d heard that they had left their normal range, but I was shocked that they’d made it to Richmond—Evening Grosbeaks hadn’t come this far south in decades.
Evening Grosbeaks on a feeder in Hillsborough. The males are bright (lower right), the females more understated (upper left and right). A Purple Finch (center), another northern visitor, has joined them. (Lane Scher)
This winter has been a special treat for birdwatchers—a huge “irruption” year for many northern bird species, like the Evening Grosbeak. Many irruptive species are in the finch family, which includes siskins, redpolls, crossbills and some grosbeaks. These species usually spend their winters in the northern US and Canada, but every so often they’ll journey farther south. What causes these birds to make massive flights some years and not others? It’s simple—food.
Many birds eat seeds from trees, which scientists call “mast,” in winter. But mast is produced irregularly in cycles—lots of mast one year, and little the next. Birds with irruptive migratory patterns move around to find food in winter. During years of large mast production, irruptive birds can stay in their preferred range farther north. But when food is scarce, they fly south.
Mast is an important food source not only for these irruptive bird species, but also for local bird species and mammals. In fact, mast cycles impact the entire forest food web. Years of high seed production, sometimes called “bumper crops”, lead to larger rodent populations, which then eat the eggs of songbirds. Mast might also be tied to outbreaks of tick-borne diseases like Lyme disease: rodent populations grow in big mast years, which means there are more hosts for ticks, leading to more disease.
Mast cycles can have such massive impacts on animal populations because the seed production of each tree species is synchronized across large geographic areas. That means that in one year, trees of a particular species in one area will produce many seeds, but in a neighboring region the same species might produce few seeds. These patterns create a food landscape that is dynamic across both space and time.
Ecologists want to understand how mast cycles work—and Duke is home to the founder and headquarters of MASTIF, a global network with exactly this goal. Dr. Jim Clark of the Nicholas School of the Environment wants to understand how climate drives mast cycles, and how these cycles will change under climate change. The MASTIF network is a huge collaboration that now includes over 2.5 million data points, each representing the mast produced by one tree in one year.
The Evening Grosbeak map from Peterson’s Field Guide to Eastern Birds shows that food-seeking irruptions can indeed reach Florida, as they have this year.
As a PhD student in Dr. Clark’s lab, I’m studying the relationship between mast cycles and the bird populations they support. I want to understand how birds respond to an environment that is constantly changing—in this case, how they respond to spatial and temporal changes in food availability. This historic irruption year is a perfect example of exactly this question: a year of low mast in the north has caused bird species to travel far outside their normal range to find food.
Interestingly, the association between these irruptive birds and food availability is so strong that it can be predicted fairly easily. The Winter Finch Forecast is based on a survey of mast crops across northern North America, which is then translated into a prediction of irruption patterns. The 2020 forecast noted that Evening Grosbeak populations would be larger this year due to outbreaks of spruce budworm, an important food source during the breeding season. This increase in the population size, combined with low winter food abundance, has led to a historic flight south.
The Clark Lab’s goal of understanding and predicting mast cycles would further our knowledge of these bird species’ unique migration patterns. With a more thorough understanding of mast patterns, we could better anticipate irruptions and implement informed conservation strategies. In addition to monitoring trees in long-term forest plots, the team uses data collected by citizen scientists through the MASTIF project on iNaturalist. With over 7,000 observations from 81 people across the world, these citizen scientists have contributed a huge amount of data.
I was thrilled to see the Evening Grosbeaks in November, and I assumed it would be my only chance. But since then, they’ve been seen throughout the Carolinas and into northern Florida. Recently, a homeowner in Hillsborough spotted a group of Evening Grosbeaks in his yard. He reported them to eBird, a citizen science project that collects data from birders around the world, and that birders use to locate rare species.
Since he reported them, birders have flocked to his yard in numbers almost as stunning as the birds themselves. Over the last few weeks, he’s counted up to 60 grosbeaks on a good day, and his yard has been visited by over 250 birders. Birders don’t want to miss this—no one knows when the next big irruption will be.
Guest post by Lane Scher, a Ph.D. student in Ecology at the Nicholas School of the Environment.
How many people have seen their cervix? Obscured from view and stigmatized socially, the cervix is critical to women’s, transgender-men’s, and non-binary folks’ health — and potential reproductive health issues. A team formed through Duke’s Center for Global Women’s Health Technologies (GWHT) has created a device that not only holds immense medical potential but the potential to empower people with cervixes across the globe: It makes visible a previously invisible organ.
Top Row, left to right: Andrea Kim, Wesley Hogan, Gita Suneja. Bottom Row, left to right: Mercy Asiedu, Nimmi Ramanujam
Nimmi Ramanujam (Ph.D.), founder of GWHT and Professor of Engineering at Duke University, heads the team. Mercy Asiedu (Ph.D.), Gita Suneja (M.D.) Wesley Hogan (Ph.D.), and Andrea Kim have all been integral members of the interdisciplinary collaboration. Dr. Suneja is Associate Professor of Radiation Oncology at the University of Utah School of Medicine and a clinical researcher. Asiedu, former PhD student with Dr. Ramanujam and current postdoc at MIT, was integral to the development of Callascope.
The Callascope allows women and others who have cervixes, along with health professionals, to perform cervical exams without use of traditional examination tools that are larger, cannot be used for self-examinations, and often scary-looking.
When Wesley Hogan, director of Duke’s Center for Documentary Studies and research professor, heard about the idea “she was hooked.” Andrea Kim graduated from Duke University in 2018. Her senior thesis was a 12 minute documentary focused on the Callascope and its potential uses. Following graduation, over the last two years, she expanded the film to a 50-minute piece titled “The (In)visible Organ” that was screened January 14, 2021. Kim moderated a panel with Ramanujam, Asiedu, Suneja and Hogan January 28th, 2021.
Callascope: A handheld device that can be used to conduct cervical screenings. All that’s needed is a smart phone.
The Callascope addresses a dire global health need for better women’s reproductive health. Further, it empowers women as self-advocates of their own gynecological and reproductive health through reinvention of gynecological examination. Cervical cells have an “orderly progression,” says Suneja, we have a “great idea” of how cells become cancerous over time, “with multiple places to intervene.” Cervical examinations, however, are necessary for assessing cervical health and potential disease progression.
Originally from Ghana, Dr. Asiedu was interested in using her engineering skills to develop technology to “improve health outcomes,” particularly in countries like her own, which may lack adequate access to preventative healthcare and could benefit most from Callascope. Many women in underserved countries, as well as underserved areas of the United States, suffer disproportionately from cervical cancer — a preventable disease.
Dr. Ramanujam, who served as a voluntary test-subject for Asiedu’s Callascope prototypes, says that it’s a really important tool “in actually changing [the cervix’s] narrative in a positive way” — it is an organ “that is indeed invisible.”
The hope is that with more awareness about and use of Callascope, cervical screenings, and vaginal health, cervixes may become more de-stigmatized and cultural norms surrounding them may shift to become more positive and open. Dr. Hogan stated that when Ramanujam pitched her the Callascope idea they were in a public restaurant. Hearing Ramanujam say words like “vagina” and “cervix” loud enough for others to hear made Hogan recognize her own embarrassment surrounding the topic and underscored the importance of the project.
The project and the team serve as a wonderful example of intersectional work that bridges the sciences and humanities in effective, inspiring ways. One example was the Spring 2019 art exhibit, developed in conjunction with the team’s work, presented at the Nasher Museum which exposed the cervix through various mediums of art.
Multidisciplinary Bass Connections research teams contributed to this work and other interdisciplinary projects focused on the Callascope. Dr. Asiedu believes documentaries like Kim’s are “really powerful ways to communicate global health issues.” Kim who directed and produced “The (In)visble Organ” hopes to continue exploring how “we can create more cultures of inclusion …when it comes to reproductive health.”
A piece of artwork from the (In)visible Organ art exhibit at Duke’s Nasher Museum in the spring of 2019.
Ramanujam emphasized the need to shift biomedical engineering focus to create technologies that center on “the stakeholders for whom [they] really [matter].” It is multi-dimensional thinkers like Ramanujam, Asiedu, Hogan, and Kim who are providing integrative and inventive ways to address health disparities of the 21st century — both the obvious and the invisible.
The beauty of research is that it allows you to take control of your own path.
“We are very lucky to be in the position to decide what we love to do and do it,” says Tai-ping Sun, a Duke biology professor studying the plant hormone GA. Researchers get to take control of their own path, she said. Every day is an opportunity to learn something new, design and analyze experiments and decide what direction to take.
Tai-ping Sun is a professor of Biology at Duke
Sun studies the GA signaling pathway because it regulates plant growth and development. She got interested in GA when she was a post-doctoral fellow at Harvard University in 1988. At the time, a lot of tools needed to be developed. As she was developing new tools to clone plant genes, she came across a GA mutant that was different. Her research is very important to understanding how the mutations in the GA signaling pathways can control the height of a plant. In fact, she says, GA mutations were one of the reasons for the success of the “Green Revolution” in the 1960s.
Sun’s current research revolves around identifying the mechanisms of the cell that make GA hormones and identifying how GA mutations have affected this pathway. Her team has identified important facets of the pathway, such as the structure and function of the nuclear receptors that allow for transcription that drives the GA response. Her team has also identified transcription factors that control the rate of the signaling pathway such as the DELLA proteins that act as master growth repressors to inhibit GA response. In fact one of her favorite discoveries is that GA triggers destruction of the DELLA proteins to activate the GA signaling pathway.
A figure from a 2004 paper by Sun on plant growth. All three of the mutants grew less well than wild type plants.
“As a scientist, the most exciting thing is to discuss experimental data, and then trying to deduce hypothesis or modify models and then come up with new experiments for testing,” she said.
But research is not without its challenges, Sun says “not everything that you do works out the first time.” That’s why she says that as a researcher the most important thing is to have an interest in your field as well as perseverance.
Guest post by Anika Jain, Class of 2021, NC School of Science and Math
We are all born with defining physical characteristics. Whether it be piercing blue eyes or jet black hair, these traits distinguish us throughout our entire lives. However, there is something that all of our attributes have in common, a shared origin: genes.
Beyond dictating our individual features, genes instruct cells to create proteins that are essential for a variety of processes, from controlling muscle function to managing digestive systems. Despite their importance in the workings of our body, genes can also code for detrimental diseases, such as Huntington’s disease or Duchenne muscular dystrophy.
Raluca Gordân, Ph.D.
These types of diseases are exactly what Raluca Gordân, Ph.D. is battling through her research. She and her group are trying to figure out how to decode the non-coding genome, the DNA apart from protein-coding genes. They are deepening their understanding of the role non-coding areas of the genome play in the expression of the coding genes and the production of proteins.
Gordân, an associate professor in biostatistics and bioinformatics at Duke, said a majority of disease-causing genetic mutations derive from the genome outside of genes.
“That is a huge search space,” she says, chuckling. “Genes only make up about 2% of the genome. If we don’t understand what those non-coding regions are doing, it’s hard to make predictions about what the mutation in those regions would be doing and how to connect that to the development of a disease.”
Gordân recently published a paper, entitled “DNA mismatches reveal conformational penalties in protein–DNA recognition,” which focuses on transcription factors and their exceptional ability to bind to mispaired DNA, misspellings that occur as DNA is copied. During regular replication, nucleotide bases (the building blocks of our DNA) are paired correctly, where adenine pairs with thymine and cytosine goes with guanine. However, when an error occurs during replication, mispairs start to appear, as adenine may pair with guanine instead.
“Normally, those are mistakes that get repaired by specific mismatch repair pathways but that repair might not happen if one of these transcription factors sits on the replication error and doesn’t allow the repair mechanism to see it,” Gordân explains. “Normally, one would expect the transcription factors not to bind to those errors. But we found that they can bind way better than their actual genomic targets.”
Modeling of the binding between mismatched DNA and transcription factors.
To expand on her computational discovery, Gordân is now following up with a study of transcription factor binding to mismatches in living cells, observing whether they adopt their usual role of regulating gene expression or contribute to the development of mutations.
Gordân’s research is a product of her passion and desire to make change. It also can be attributed to a series of realizations she made during college and inspirational mentors who guided her along the way.
While pursuing her undergraduate degree, Gordân was a purely computer science major, concentrating on cryptography. However, as she was nearing the end of her four years of college, she soon found herself yearning for the opportunity to do more. She began looking into machine learning applications and enrolled in a course based around genetic algorithms which she credits for launching her career path.
At that point, she attained what she describes as her “first taste of genetics” and her interest in bioinformatics was irrevocably piqued. Thereafter, Gordân applied for a PhD at Duke, where she worked with advisor Alex Hartemink investigating transcription factor proteins in regulatory genomics. At Duke, her work was primarily computational. But with her postdoctoral advisor Martha Bulyk of Harvard Medical School, Gordan was exposed to the more experimental aspects of biology.
Today, she recognizes these experiences as integral to her ongoing research, which requires her to frequently iterate between observational approaches and computational work.
Gordân is acclimating to the newly quarantined world. While she strives to continue her research, in the pandemic, it has changed her routine.
“I think what was affected a lot since the pandemic started is the fact that we don’t meet in person,” she says. “A lot of the quick progress was being made when we were in the same physical space and were able to get feedback immediately, with students learning about each other’s results in the lab, in real time. That was replaced with Zoom meetings, where students get to see the other students’ results mainly at lab meetings, weeks or months later. Those continuous discussions that were going on in the lab all the time. We’re missing that.”
Gordân offered some thoughtful parting advice to aspiring computational biologists, like me.
“I was trained as a computer scientist, so I wasn’t really sure about experimental work. But after actually doing the experimental work, I realized how much value there is in doing both,” she said. “You have to pick what you’re strongest at, either the computational or experimental part, but you should not be afraid of the other side.”
Guest Post by Akshra Paimagam, Class of 2021, NC School of Science and Math
Meet Claire Engstrom, a Senior from Pasadena California. Claire is a Biology major who works in the Gersbach Lab at Duke.
Claire first got involved with on-campus research through her pre-orientation program, PSearch that introduces incoming first-years to undergraduate research. Following her experience in PSearch, Claire got her first work-study research position in the Tung Lab where she worked closely with Jenny Tung, an Associate Professor in the Departments of Evolutionary Anthropology and Biology at Duke and a Faculty Associate of the Duke University Population Research Institute.
In the Tung Lab, Claire’s research focused on how DNA methylation is passed through generations. Essentially looking at the inheritance of DNA whose methylation was impacted by environmental factors and how that affects future generations.
Duke has research opportunities available in all disciplines as well as across departments. Approximately 53% of undergraduates graduate with research experience. Not only can students participate in groundbreaking research, but they can receive funding from the university as well to support the work they are doing.
Within the Biology department, there is a fellowship called B-SURF, the Biological Sciences Undergraduate Research Fellowship, an 8-week summer research program for rising sophomores. Claire applied for and was accepted to the fellowship and placed in one of Duke’s biomedical science laboratories. She also received a $4,000 stipend for her summer research.
Claire was placed in Charles Gersbach’s Lab focused on researching Genome Editing for Gene and Cell Therapy. Dr, Gersbach is a Rooney Family Associate Professor of Biomedical Engineering and has conducted groundbreaking work in genome editing.
Members of the Gersbach Lab in Fall 2019
Gersbach is doing research in several different domains of biomedical engineering. Claire’s project focuses on using CRISPR-Cas9, a technology that allows scientists to change an organism’s DNA using clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. faster, cheaper, more accurate, and more efficient than other existing genome editing methods.
Prior to joining his lab, Claire had already heard a lot about Gersbach in her course Biology 201 as well as through reading his papers. The project she would spend the next two and a half years working on focused on using and optimizing CRISPR-Cas9 to treat Duchenne’s Muscular Dystrophy and lessen the severity of the symptoms.
Duchenne’s Muscular Dystrophy is a muscle wasting disease that affects one in every five thousand male births.
“People are diagnosed when they are around five and then they lose the ability to walk and their heart can’t pump blood because of the lack of muscles.” Claire explained.
“CRISPR-based genome editing restores dystrophin expression in mouse models of Duchenne muscular dystrophy. Cross-sections of muscle tissue where the dystrophin protein has been labeled green, including normal, healthy tissue (left), tissue from a mouse model of Duchenne muscular dystrophy (middle), and tissue from the same mouse model that has been treated with the CRISPR gene editing system (right). Nelson et al., Science (2016)”
Thus, those affected often die in early adulthood despite current advances in cardiovascular and respiratory treatments. Duchenne’s Muscular Dystrophy generally occurs as a result of a frameshift mutation of the dystrophin gene. As a result, one’s muscles can no longer connect to anything making it nearly impossible to contract and function properly. In the Gersbach lab they are trying to treat the mutation by using CRISPR-Cas9 to remove an exon or coding region of the gene in order to shift the reading frame back into its normal place.
This shift produces a less severe phenotype that lessens the effects of Duchenne’s Muscular Dystrophy. The result will significantly improve the quality of life and life spans for affected patients.
Claire will be continuing her work in the Gersbach lab full time in Spring 2021 as she graduated early, with distinction in the Fall. Her thesis on the work she did in the Gersbach lab was recently approved and her results will be published in a larger paper in the future. After this year she plans to take a gap year an then return to California to hopefully attend grad school and pursue a Ph.D. in Biology.
New study casts doubt on links between personality and brain structure. MRI scan courtesy of Annchen Knodt, Duke University
We know personality comes from the brain, but does that mean the brain’s shape and composition affect personality as well?
Previous studies have attempted to find links between brain structure and personality types, but new data indicates otherwise. A new study, the largest of its kind, suggests these links may not be so strong after all. In fact, they may not even exist.
Recently Duke researchers, led by Reut Avinun Ph.D., a postdoctoral associate at Professor Ahmad Hariri’s lab, analyzed the MRI scans of over a thousand people to determine potential links between personality and brain shape.
Although there are many personality neuroscience studies, consistent and reliable findings have not been established. While most previous studies used less than 300 individuals, this study has a large sample of 1,107 individuals. Additionally, this research comprehensively measures personality with 240 items.
“When I got into the field, people were collecting data sets with only 10 people and doing analysis with only 20 participants,” said Avram Holmes, an asssociate professor of psychology at Yale who was not involved in the study.
Personality studies such as this typically use the “Big Five” personality traits: neuroticism, extraversion, agreeableness, conscientiousness, and openness-to-experience. Extraverted people tend to be outgoing and social and those with high openness-to-experience are imaginative, curious, and enjoy trying new things. High neuroticism and low conscientiousness have been associated with negative health behaviors such as smoking. These were even connected to negative life outcomes, such as depression, anxiety, and poor sleep. By understanding what underlies these behaviors, scientists may be able to better treat them.
For brain shape, Avinun and her colleagues examined brain morphometry, cortical thickness, cortical surface area, subcortical volume, and white matter microstructural integrity. She used a univariate approach, looking at the relationship between one phenotype and one behavior. Statistical analysis also accounted for the factors of race/ethnicity, sex, and age.
Last year, researchers published a paper finding 15 correlations between specific personality traits and neuroanatomical structures. However, Avinun’s new research found that none of these connections held true in the large Duke Neurogenetics Study sample.
When scientists analyze an MRI dataset, there is a lot of freedom in the phenotypes collected and the types of analyses. “With so many degrees of investigative freedom and the expectation that you should see something there, researchers may accidentally find false positives. It’s easy to fall into the trap of making a story about why the effect has this particular brain pattern and see an association that doesn’t exist,” Holmes explained.
Ultimately, Avinun found no links between the Big Five personality traits and multiple features of brain structure.
While this may seem anticlimactic, even null findings are incredibly useful and could lead to recommendations to future research in this area. By showing that links between brain morphometry and personality tend to be small, this research may push the field toward studies with larger samples and guidelines for higher replication rates.
“The brain is plastic and it is affected every day by our experiences, so expecting to find straightforward associations between brain morphometry and personality traits may be too naïve,” Avinun said. “We are beginning to realize that large samples and multivariate methods are needed in neuroscience. Trying to understand what makes us who we are is exciting. Research is really challenging as the field is constantly changing, but it is constantly improving as well.”
Niba Nirmal is a multimedia science communicator based in San Francisco, CA. She graduated in the Duke class of 2020, with a Master’s degree in Genetics. Find samples of her work at www.notesbyniba.com
We’ve all heard the term “survival of the fittest,” which scientist Charles Darwin famously coined to explain how organisms with heritable traits that give them an advantage — such as avoiding predators or beating out others for the chance to mate — are able to survive and pass on these advantageous traits to their offspring.
In his talk with ClubEvMed last Tuesday, Brian Hare of Duke Evolutionary Anthropology explained key points from his new book that he co-authored with his wife and research partner, Vanessa Woods, entitled Survival of the Friendliest: Understanding Our Origins and Rediscovering Our Common Humanity.
Image from Penguin Random House
The term “fittest” is often associated with animals who are physically stronger or of more value than others, but being “fit” can also include an organism’s ability to communicate well with others in its group, which can provide an evolutionary advantage. For example, more social animals can form alliances with each other and protect each others’ young, so the whole population stays stronger in terms of number.
Hare cited a comparison between chimpanzees and bonobos, both of which have the potential for infanticide by aggressive males in a group. However, bonobos have zero cases of infanticide because female bonobos are able to communicate well and form alliances to protect each others’ young from aggressive males. Since the high cost of aggression for males outweighs the benefit, the males are friendlier, and the young bonobos survive. While this is a specific case with wild animals, other species have adopted social skills as a method of survival through domestication or self-domestication.
Image from brianhare.net
Hare referred to dogs as “exhibit A” of survival of the friendliest via domestication, because humans have bred dogs that are more playful, approachable and patient for centuries. Dogs are exceptionally good at understanding, responding to and communicating with humans as a result of domestication. Hare also explained one Russian study in which they began selecting foxes based on their friendliness towards people. They bred the most friendly foxes together and then compared the friendliness of their offspring to the offspring of randomly bred foxes. The results showed that friendlier foxes differed in physiology in addition to behavior, and were better at cooperating and communicating with humans. This is an example of self-domestication, which changes development patterns and has increased fitness via friendliness. Friendliness in this case means skill in cooperating and communication.
Survival of the Friendliest argues that humans today are the friendliest species of human, which may be why we have lasted so long evolutionarily. However, with the new type of friendliness also comes a new type of aggression. Mother bears are kind and nurturing to their cubs, but also have the most potential for aggression when they feel their cubs are threatened. Similarly in humans, when we feel people who share our identity are threatened, we want to protect those individuals.
Hare and Woods reason that this desire to protect also reduces our ability to cooperate or communicate with those who we feel threaten us or threaten our “group”— whether this be our family, our race or another trait. When our ability to communicate is reduced, we begin to dehumanize those who we feel threaten the people who share our identity. This then becomes a cycle, where people dehumanize those who they believe are dehumanizing them.
In order to stop this cycle, Hare and Woods argue that humans will need to alter their view of who they believe “belongs” to their group to include more people. We need to communicate openly and build a desire to protect other humans, rather than dehumanize them.
After my freshman fall, I swore I’d never take another 8AM class. Yet, when a microbiology lab was the only opportunity I had for an in-person course in Duke’s disrupted Fall 2020 semester, I jumped at the chance to take it. Wednesdays have become my on-campus days, and though they start at 7AM and are often jam-packed until 7PM, they are my favorite days of the week.
I’m usually the first to arrive in sub-basement of the Biological Sciences building on Wednesdays. As my six lab-mates join me, we stand in line on top of stickers spaced according to 6-foot social-distancing guidelines and talk about questions from class or the lab we’re going to perform that day. Sometimes it’s difficult to hear one another through our masks. When our TA is ready for us to enter the classroom, we do so one at a time, only after she’s verified our Symptom Monitoring status and taken our temperature.
Stickers marking 6-ft distances for safety. The lab layout with seating arrangements according to Covid guidelines.
Our lab stations are spaced so that we are appropriately distanced from one another, but able to work and collaborate as a team as best we can. We have a no-contact drop-zone for placing and picking up shared lab items, though each students’ space is equipped with most everything we need for our lab on most occasions. The stations are close enough so that we can chat, compare results, and ask each other for assistance as we work. Everyone wears a face shield over a face mask. Each lab session we exchange our “home” face mask for a disposable “lab” face mask. Since we work with potentially pathogenic microbes, this step is for our safety to make sure we don’t carry harmful bacteria out of our lab space. Unlike previous years, gloves are worn at all times, but the lab coats we wear have always been a standard part of the microbiology lab attire.
The infamous “no contact drop zone” for use of shared materials during lab.
What used to be two, two-hour lab sessions twice a week has been condensed into a single four-hour lab-session to minimize exposure to one another. At the beginning of the semester it felt strange and uncomfortable to wear a mask for the whole lab period and for the rest of the day on campus. But like many changes due to Covid-19, I’ve simply gotten used to it. It’s worth it to have face-to-face interactions with fellow students and to have hands-on experience in the lab. In many ways, these experiences feel much more real and meaningful than my fully online classes, in which I interact exclusively virtually with peers and instructors.
This semester we’ve also been doing science at home, having been tasked with an independent research project to be performed outside of lab. The kitchen in my apartment has become a makeshift space for inoculating TSA plates and perplexing my roommate with my experiment.
At home experimental set-up and data collection in my apartment.
After microbiology, I grab a quick lunch at West Union…which I’m still figuring out how to navigate. There’s more online ordering and different routes for lines I haven’t gotten used to. Though it’s significantly less crowded than it used to be – which has its advantages – the energy and fervor that made up Duke is certainly missing. Though I feel it in spurts when I run into the rare upperclassman on the Plaza or in the Bryan Center while trying to find a spot to study, campus is unequivocally not the same.
I leave the central part of campus and return to the basement of BioSci to work in my research lab, the Steve Nowicki Lab. According to our Covid plan, a grad student must be present to supervise me at all times and each of us works on opposite sides of the lab space. It’s really not all that different than it used to be.
In the Nowicki Lab, I test the categorical color perception of Zebra finches. After being trained for the trials, the birds are tested to see if they can detect color differences between a background color and two “odd color out” chips. Colors one and eight are most starkly different, but when comparing colors seven and eight, for example, I sometimes struggle to tell the two colors apart.
Background color 8 versus odd-color-out 7. Can you tell the difference? (Color 7 is in wells 1 and 7)
Following a five-month hiatus from running trials, I was pleasantly surprised to find myself in the rhythm of things with only a few marginal mishaps. Within a half-hour of being back in the lab, I was running experiments at full speed again. For a moment it felt like I’d never left, and like it could have been the Wednesday before spring break, before the pandemic took full effect. Sometimes still when I’m running trials, I imagine I could walk out of BioSci’s basement and find that everything would be just as it had been when I left in March.
I spend three hours with the birds, running a refresher round followed by five experimental trials. And usually, I listen to podcasts while I work. The time passes quickly, sometimes more quickly than I’d hope.
Example of bird during experiments.
Since I’m already on campus, most Wednesdays I stick around and attend my online history seminar from a spot around campus. Though I can’t perch myself on the third floor of Perkins Library these days, I’ve found a new spot I like on the second level of the Bryan Center and I’ve made it work for me.
On Wednesdays, I am reminded of the reasons I fell in love with Duke and of all the things I miss about it in these strange and uncertain times. I wonder if the Duke I knew will ever be the same. Or if something has fundamentally shifted in our institution, and more largely in each of us individually, that only leaves us with a path forward to a new Duke, rather than a return to the old.
I am team Crystal Violet #2 and this is my bag for placing my “home mask” in when gearing up for lab.
As I return to my car in Blue Zone, I take a longing look at the Chapel. Then I make my way to my car, turn on some tunes for the drive home, and patiently wait for my alarm to wake me at 7AM the next Wednesday morning.
Most of the time I’m left thinking about the Duke that used to be, despite the fact that I certainly admire the socially-responsible and safe Duke that is. We’re doing well, all things considered. But still, it’s not the same. The Duke that the first years know is not the Duke I remember.
By Anna Gotskind
