Following the people and events that make up the research community at Duke

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Following In The Footsteps of Elephants

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Imagine for a moment that you’re 6,000 pounds, living in one of the wildest places on Earth, with no schedule, nowhere to be. How do you decide where to spend your time? Where to go next? Do you move where food is most plentiful? Is water your main priority?

Amelia Meier in the field.

These are some of the questions addressed by Duke Ph.D. candidate Amelia Meier and former postdoctoral researcher Dr. Chris Beirne in Dr. John Poulsen’s lab. Their recent study published in Trends in Ecology and Evolution focused on the African forest elephant–the slightly smaller yet still undeniably huge cousin of the savanna elephant.  

The team wanted to know what influences certain aspects of elephant behavior. Specifically, how much climate and resource availability drives elephant movement and influences their diet. To do this, the team looked at fruit abundance (a high-energy staple of elephants’ diets), water availability from rainfall, and elephant identity and how those factors affect how an individual moves and eats.

One might think that such a massive animal is easy to spot in the forest. However, the dense vegetation of Central African rainforests can be an impenetrable wall, allowing the massive animals to move unseen through the forest, leaving broken branches and steaming dung piles in their wake.

To better track them, the researchers fitted individual elephants with GPS collars that turn an iPhone into an elephant-tracking tool. This also allowed trackers to follow the elephants at a distance and avoid conflict with the sometimes temperamental animals.

Collared elephant, Marijo, (left) enjoying the rich minerals found at the Langoue Bai forest clearing.

Meier, Beirne, and colleagues also wanted to know more about the diets of the tracked elephants to see if what they ate changed with how much fruit is available. This less-than-glamorous job was done by dissecting fresh dung piles, estimating the proportions of leafy and woody material, and counting the number of seeds in each one.

Tropical rainforests are lush, yet have patchy resources, making it important for many frugivores to have flexible diets. Some trees only produce fruit in the wet season. Others fruit every other year. To gauge fruit availability, the research team conducted “fruit-walks” at the beginning and end of each day of following an elephant, in which trackers counted all of the ripe fruit on the ground.

A key finding of the study was that the most important factor driving movement was an elephant’s individuality; some respond to food or water availability differently and some simply move around more than others.

Field researcher Marius Edang getting the straight poop on elephant diets.

Interestingly, elephants appear to be affected by resources differently depending on the timescale the authors looked at. Water was important on both a day-to-day and month-to-month basis. Yet on a daily basis, fruit and water were more equally matched, with water still maintaining a slight lead.

Fruit availability was also critical in determining how much elephants moved and what they ate. When there was more fruit available, the elephants ate more fruit, as evidenced by the proportion of seeds in dissected dung piles.

Aside from being an awe-inspiring species, forest elephants are important to the health of their native ecosystems. They are unwitting gardeners, planting seeds of the fruits they consume in piles of dung and giving those seeds a better chance of survival. That’s part of why understanding what motivates forest elephant movement is more than the satisfaction of an elephant enthusiast’s curiosity; it is critical to managing and conserving a species that is vulnerable to multiple threats from humans.

Meier’s dissertation research focuses on elephant social behavior and the effects of human disturbance on elephant social groups, allowing her to pursue her long-term interest in animal behavior with a practical conservation application.

“I was living in Congo and I knew I wanted to keep working in the region. There, you have elephants–this amazing, highly intelligent, social species that is surrounded by conflict.”

Poachers seek elephants for their ivory tusks, which are valuable on the black market. The pachyderms are also prone to conflict with humans when they start foraging in village plantations, destroying crops and damaging livelihoods.

The team’s findings open the way for new questions about why different elephants exhibit different patterns of movement. What underlying factors affect behavior, and why? Does it have to do with age? Sex? Their social environment?

These questions remain unanswered for now, but the work of Meier and colleagues represents a critical step in understanding elephant behavior to improve forest elephant management and conservation strategies.

Guest Post by Anna Nordseth, a Ph.D. Candidate in the Nicholas School of the Environment

Duke Scientists Studying the Shape of COVID Things to Come

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The novel coronavirus pandemic has now resulted in more than 3 million confirmed cases globally and is pushing scientists to share ideas quickly and figure out the best ways to collaborate and contribute to solutions.

SARS-CoV-2 surface proteins illustrated by We Are Covert, via Wikimedia Commons

Recently, Duke researchers across the School of Medicine came together for an online symposium consisting of several short presentations to summarize the latest of what is known about the novel coronavirus, SARS-CoV-2.

This daylong event was organized by faculty in the Department of Molecular Genetics and Microbiology and researchers from different fields to share what they know about the virus and immunity to guide vaccine design. This conference highlighted the myriad new research pathways that Duke researchers are launching to better understand this pandemic virus.

One neat area of research is understanding viral processes within cells to identify steps at which antivirals may block the virus. Stacy Horner’s Laboratory studies how RNA viruses replicate inside human cells. By figuring out how viruses and cells interact at the molecular level, Horner can inform development of antivirals and strategies to block viral replication. Antivirals stop infections by preventing the virus from generating more of copies of itself and spreading to other cells. This controls damage to our cells and allows the immune system to catch up and clear the infection.

At the symposium, Horner explained how the SARS-CoV viral genome consists of 29,891 ribonucleotides, which are the building blocks of the RNA strand. The viral genome contains 14 areas where the RNA code can be transcribed into shorter RNA sequences for viral protein production. Though each RNA transcript generally contains the code for a single protein, this virus is intriguing in that it uses RNA tricks to code for up to 27 proteins. Horner highlighted two interesting ways that SARS-CoV packs in additional proteins to produce all the necessary components for its replication and assembly into new viral progeny.

The first way is through slippery sequences on the RNA genome of the virus. A ribosome is a machine inside the cell that runs along a string of RNA to translate its code into proteins that have various functions. Each set of 3 ribonucleotides forms one amino acid, a building block of proteins. In turn, a string of amino acids assembles into a distinct structure that gives rise to a functional protein.

One way that SARS-CoV-2 packs in additional proteins is with regions of its RNA genome that make the ribosome machinery slip back by one ribonucleotide. Once the ribosome gets offset it reads a new grouping of 3 ribonucleotides and creates a different amino acid for the same RNA sequence. In this way, SARS-CoV-2 makes multiple proteins from the same piece of RNA and maximizes space on its genome for additional viral proteins.

An example of an RNA ‘hairpin’ structure, which might fool a ribosome to jump across the sequence rather than reading around the little cul de sac. (Ben Moore, via Wikimedia Commons)

Secondly, the RNA genome of SARS-CoV-2 has regions where the single strand of RNA twists over itself and connects with another segment of RNA farther along the code to form a new protein. These folds create structures that look like diverse trees made of repetitive hairpin-like shapes. If the ribosome runs into a fold, it can hop from one spot in the RNA to another disjoint piece and attach a new string of amino acids instead of the ones directly ahead of it on the linear RNA sequence. This is another way the SARS-CoV-2 packs in extra proteins with the same piece of RNA.

Horner said a step-by-step understanding of what the virus needs to survive at each step of its replication cycle will allow us to design molecules that are able to block these crucial steps.

Indeed, shapes of molecules can determine their function inside the cell. Three Duke teams are pursuing detailed investigation of SARS-CoV-2 protein structures that might guide development of complementarily shaped molecules that can serve as drugs by interfering with viral processes inside cells.

Some Duke faculty who participated in the virtual viral conference. (L-R from, top) Stacy Horner, Nick Heaton, Micah Luftig, Sallie Permar, Ed Miao and Georgia Tomaras. (image: Tulika Singh)

For example the laboratory of Hashim Al-Hashimi, develops computational models to predict the diversity of structures produced by these tree-like RNA folds to identify possible targets for new therapeutics. Currently, the Laboratories of Nicholas Heaton and Claire Smith are teaming up to identify novel restriction factors inside cells that can stop SARS-CoV-2.

However, it is not just the structures of viral components expressed inside the cells that matter, but also those on the outside of a virus particle. In Latin, corona means a crown or garland, and coronaviruses have been named for their distinctive crown-like spikes that envelop each virus particle. The viral protein that forms this corona is aptly named the “Spike” protein.

This Spike protein on the viral surface connects with a human cell surface protein (Angiotensin-converting enzyme 2, abbreviated as ACE2) to allow the virus to enter our cells and cause an infection. Heaton proposed that molecules designed to block this contact, by blocking either the human cell surface protein or the viral Spike protein, should also be tested as possible therapies.

One promising type of molecule to block this interaction is an antibody. Antibodies are “Y” shaped molecules that are developed as part of the immune response in the body by the second week of coronavirus infection. These molecules can detect viral proteins, bind with them, and prevent viruses from entering cells. Unlike several other components on our immune defense, antibodies are shaped to specifically latch on to one type of virus. Teams of scientists at Duke led by Dr. Sallie Permar, Dr. Georgia Tomaras, and Dr. Genevieve Fouda are working to characterize this antibody response to SARS-CoV-2 infection and identify the types of antibodies that confer protection.

Infectious disease specialist Dr. Chris Woods is leading an effort to test whether plasma with antibodies from people who have recovered can prevent severe coronavirus disease in acutely infected patients.

Indeed, there are several intriguing research questions to resolve in the months ahead. Duke scientists are forging new plans for research and actively launching new projects to unravel the mysteries of SARS-CoV-2. With Duke laboratory scientists rolling up their sleeves and gowning up to conduct research on the novel coronavirus, there will be soon be many more vaccine and therapeutic interventions to test.

Guest post by Tulika Singh, MPH, PhD Candidate in the Department of Molecular Genetics and Microbiology (T: @Singh_Tulika)

A Day of STEM for Girls

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On any average weekday at Duke University, a walk through the Engineering Quad and down Science Drive would yield the vibrant and exciting sight of bleary-eyed, caffeine-dependent college students heading to labs or lectures, most definitely with Airpods stuck in their ears.

But on Saturday, February 22nd, a glance towards this side of campus would have shown you nearly 200 energetic and chatty female and female-identifying 4th to 6th graders from the Durham area. As part of Capstone, an event organized by Duke FEMMES, these students spent the day in a series of four hands-on STEM activities designed to give them exposure to different science, technology, engineering, and math disciplines.

Nina MacLeod, 10, gets grossed out when viewing fruit fly larvae through a microscope while her guide, Duke first-year Sweta Kafle, waits patiently. (Jared Lazarus)

FEMMES, which stands for Females Excelling More in Math, Engineering, and Science, is an organization comprised of Duke students with the aim of improving female participation in STEM subjects. Their focus starts young: FEMMES uses hands-on programming for young girls and hosts various events throughout the year, including after-school activities at nearby schools and summer camps. 

Capstone was a day of fun STEM exposure divided into four events stationed along Science Drive and E-Quad — two in the morning, and two in the afternoon, with a break for lunch. Students were separated into groups of around eight, and were led by two to three Duke undergraduates and a high school student. The day started bright and early at 8:45 A.M with keynote speaker Stacy Bilbo, Duke professor of Psychology and Neuroscience. 

Staci Bilbo

Bilbo explained that her work centers around microglial cells, a type of brain cell. A series of slides about her journey into a science career sparked awe, especially as she remarked that microglial cells are significant players in our immune system, but scientists used to know nearly nothing about them. Perhaps most impactful, however, was a particular slide depicting microglial cells as macrophages, because they literally eat cellular debris and dead neurons.

A cartoon depiction of this phenomenon generated a variety of reactions from the young audience, including but not limited to: “I’m NEVER being a doctor!”, “I wish I was a microglial cell!”, “Ew, why are brains so gross?”, and “I’m so glad I’m not a brain because that’s SO weird.”

Even in 2020, while fields like medicine and veterinary science see more women than men, only 20% of students that earn bachelor’s degrees in physical sciences, math, and engineering disciplines are female. What accounts for the dramatic lack of female participation in STEM disciplines? The reasons are nuanced and varied. For example, according to a 2010 research report by the American Association of University Women, girls tend to have more difficulty acquiring spatial thinking and reasoning skills – all because of the type of play young female children are more likely to engage in. 

Durham area students learned how to perform a blood pressure check during a FEMMES session taught by Duke EMS, an all-volunteer, student-run division of the police department and Duke Life Flight. Duke senior Kayla Corredera-Wells (center) put the blood pressure cuff on sophomore Pallavi Avasarala. (Jared Lazarus)

This creates a chicken-and-egg story: girls don’t enter STEM at the same rate as their male counterparts, and as a result, future generations of girls are discouraged from pursuing STEM because they don’t see as many accomplished, visibly female scientists to look up to. Spaces like Capstone which encourage hands-on activity are key to exposing girls to the same activities that their male counterparts engage in on a regular basis – and to exposing girls to a world of incredible science and discovery led by other females. 

After Bilbo’s talk, it was off to the activities, led by distinguished female professors at Duke — a nod to the importance of representation when encouraging female participation in science. For example, one of the computer science activities, led by Susan Rodger, taught girls how to use basic CS skills to create 3-D interactive animation.

An introduction to categorizing different minerals based on appearance was led by Emily Klein, while one of the medicine-centered activities involved Duke EMS imparting first aid skills onto the students. 

For one of the biology-themed activities, Nina Sherwood and Emily Ozdowski (dubbed “The Fly Ladies”) showed students fruit flies under a microscope. The activity clearly split the group: girls who stared in glee at unconscious flies, shrieking “It’s SO BIG, look at it!” and girls who exchanged disgusted looks, edging their swivel chairs as far as physically possible from the lab benches. Elizabeth Bucholz, a Biomedical Engineering professor, led one of the engineering activities, showing students how CT scans generate images using paper, a keychain light and a block (meant to represent the body). In math, meanwhile, Shira Viel used the activity of jump-roping to show how fractions can untangle the inevitable and ensuing snarls.

The day definitely wasn’t all science. During lunch in LSRC’s Love Auditorium, most groups spread out after scarfing down pizza and spent intense focus over learning (and recording) TikTok dances, and when walking down Science Drive under blue and sunny skies, conversations ranged from the sequins on someone’s Ugg boots to how to properly bathe one’s dog, to yelling erupting over someone confidently proclaiming that they were a die-hard Tar Heel.

Nina Sherwood, Associate Professor of Biology, showed Emma Zhang, 9, some fruit flies, which we study because they share 75% of their genes with humans. (Jared Lazarus)

A raffle at the end of the day for the chance to win Duke merchandise inspired many closed eyes and crossed fingers (“I want a waterbottle so bad, you have no idea!”) And as newfound friends said goodbye to each other and wistfully bonded over how much fun they had at the end of the day, one thing was clear: events like Capstone are crucial to instilling confidence and a love of STEM in girls. 

By Meghna Datta

Paleo Fact and Fiction: the Key to Being Healthy

Humans have conquered smallpox and drastically reduced child mortality rates, yet we now face problems never seen before. Conditions like heart disease, obesity, cancer, and diabetes pose serious threats to our health. How can we overcome them? The answer may lie in our past.

Herman Pontzer, an associate professor of evolutionary anthropology at Duke, thinks we have something to learn by looking at hunter gatherers.

For most of human evolution, we had to work for our food. Recent developments like supermarkets and cities are strange and have flipped the script on daily life. Pontzer believes if we could live more like our ancestors, maybe we wouldn’t get sick.

Pontzer started off by studying a hunter gatherer group in Tanzania known as the Hadza. The Hadza cling tight to cultural traditions and live off the land in the African savannah. There are no domesticated animals, no guns, and no vehicles. Women spend their days digging for fibrous tubers and gathering berries and baobab fruits. When men aren’t hunting game, they collect honey. Honey plays a major role in the Hadza diet — around 15-20% of their caloric intake.

The Hadza live a very active lifestyle. They walk between 13,000 and 20,000 steps a day, compared to the generic Fitbit goal of 10,000 steps (which most of us don’t even meet, if we’re being honest).

Curious to see if the Hadza’s vigorous activity levels had something to do with their superior health, Pontzer used the doubly labeled water technique to measure total energy expenditure. Shockingly, he found that Hadza and Americans burn the same amount of calories on average.

All our lives we’ve been told exercise converts to burned calories. But evidence from the Hadza tells us this is not the case. What really happens is natural systems in our body adjust to suppress other activity, keeping total expenditure constant. This means that exercise alone is an ineffective tool for weight loss. But don’t quit the gym quite yet — while the Hadza spend most of their total energy being active, an inactive body will spend it on unhealthy things such as inflammation and stress reactivity. This constrained energy mechanism makes exercise essential for overall health. But in the words of Pontzer, “in order to end obesity, we need to fix our diet.”

Image result for paleo diet

The idea that the “paleo diet” is necessarily low-carb is a myth, Pontzer says. Hadza rely heavily on starches and fructose for sustenance. Furthermore, what you eat as a hunter gatherer is entirely dependent on geographical location. Hunter gatherer diets do things in common, though: they eat no processed foods, and energy dense foods are hard to come by. 

Never before have we had so much food high in energy available at such a low effort. In supermarkets, the cheapest food is the most rich in energy. In the wild, it’s the complete opposite. Pontzer says, “traditional diets are diverse, modern diets are perverse.”

Image result for supermarket cereal aisle

He calculated that an American can get twenty times as much food energy in an hour’s work as a Hadza could with the same effort. Plus, the Hadza don’t have irresistible Doritos they can’t stop eating. When the Hadza are full, they’re full.

The Hadza are naturally protected from the same “diseases of civilization” that we are likely to die from. A beautiful combination of diet and how they expend energy provides a shield that modernization seems to have taken from us. Energy has become too available. But staying healthy is still in our control. It’s about finding the right balance of exercise and eating right.  

There is still a lot to be learned from hunter gatherer societies. For now, let the Hadza inspire you to get outside, get active, and cut out processed foods!

Polymath Mae Jemison encourages bolder exploration, collaboration

Photo from Biography.com

“I don’t believe that [going to] Mars pushes us hard enough.” This was just one of the bold, thought-provoking statements made by Dr. Mae Jemison, who came to speak at Duke on Monday, February 24 as part of the 15th annual Jean Fox O’Barr Distinguished Speaker Series, presented by Baldwin Scholars.

Dr. Jemison is at the pinnacle of interdisciplinary engagement—though she is most famous for serving as a NASA astronaut and being the first African American woman to go into space, she is also trained as an engineer, social scientist and dancer. Dr. Jemison always knew that she was going to space—even though there were no women or people or color participating in space exploration as she was growing up.

Dr. Jemison says that simply “looking up” brought her here. As a child, she would look up at the sky, see the stars and wonder if other children in other places in the world were looking at the same view that she had. Growing up in the 1960’s instilled into Dr. Jemison at an early age that our potential is limitless, and the political culture of civil rights, changing art and music and decolonization were all about “people declaring that they had a right to participate.” 

Photo courtesy of Elizabeth Roy

One of the biggest pieces of advice that Dr. Jemison wanted to impart on her audience was the value of confidence, and how to build confidence in situations where people are tempted to feel incapable or forget the strengths they already possess. “They told me if I wanted to lead projects I needed an M.D.,” Dr. Jemison explained. “I went to medical school because I know myself and I knew I would want to be in charge one day.” 

At 26 years old, Dr. Jemison was on call 24 hours a day, 7 days a week, 365 days a year as the Area Peace Corps Medical Officer for Sierra Leone and Liberia. She described a case where a man came back with a diagnosis of malaria from Senegal. When Dr. Jemison first took a look, the diagnosis seemed more likely to be meningitis. After making an “antibiotic cocktail,” from what she had on site, she realized this man might lose his life if they didn’t get him to a better hospital. At this point, Dr. Jemison wanted to call a military medical evacuation, and she had the authority to do it. However, another man working with her suggested calling a doctor in Ivory Coast, or a doctor at the hospital in Germany to see what he thought before making the evacuation. Dr. Jemison knew what the patient needed in this situation was to be flown to Germany regardless of the cost of the evacuation. In reflecting on this experience, she says that she could have given someone else her authority, but letting her confidence in herself and what she knew was the right thing to do would have negatively impacted her patient. 

So, how do you maintain confidence? According to Dr. Jemison, you come prepared. She knew her job was to save people’s lives, not to listen to someone else. Dr. Jemison also admonished the audience to “value, corral and protect your energy.” She couldn’t afford to always make herself available for non-emergency situations, because she needed her energy for when a patient’s life would depend on it. 

Photo courtesy of Elizabeth Roy

Dr. Jemison’s current project, 100 Year Starship, is about  trying to ensure we have the capabilities to travel to interstellar space. “The extreme nature of interstellar hurdles requires we re-evaluate what we think we know,” Dr. Jemison explained. Alpha Centauri, the next closest star, is more than 25 trillion miles away. Even if we go 10% the speed of light, it will still take us 50 years to get there. We need to be able to travel faster, the vehicle has to be self-replenishing, and we have to think about space-time changes. What Dr. Jemison calls the “long pole in the tent” is human behavior. We need to know how humans will act and interact in a small spaceship setting for possibly decades of space travel. Dr. Jemison is thinking deeply about how we can apply the knowledge we already possess to fix world problems, and how we can start preparing now for problems we may face in the future. For example, how would health infrastructure in deep space look different? How would we act on a starship that contains 5,000 people when we can’t figure out how to interact with each other on the “starship” we’re on now?

Returning to the childhood love for stargazing that brought her here, Dr. Jemison discussed towards the end of her talk that a stumbling block for the majority of people is insufficient appreciation of our connection across time and space. She has worked with a team to develop Skyfie, an app that allows you to upload photos and videos of your sky to the Sky Tapestry and explore images other people in different parts of the world are posting of their sky. Dr. Jemison’s hope is this app will help people realize that we are interconnected with the rest of the universe, and we won’t be able to figure out how to survive as a species on this planet alone. 

By Victoria Priester

#UniqueScientists Is Challenging Stereotypes About Who Becomes a Scientist

University of North Carolina cell biologist Efra Rivera-Serrano says he doesn’t look like a stereotypical scientist: he’s gay, Puerto Rican, and a personal trainer.

Known on Twitter as @NakedCapsid or “the guy who looks totally buff & posts microscopy threads,” he tweets about virology and cell biology and aims to make science more accessible to the non-science public.

But science communication encompasses more than posting the facts of viral transmission or sending virtual valentines featuring virus-infected cells, Rivera-Serrano says. As a science communicator, he’s also committed to conveying truths that are even more rarely expressed in the science world today. He’s committed to diversity.

Rivera-Serrano’s path through academia has been far from linear — largely because of the microaggressions (which are sometimes not so micro) that he’s faced within educational institutions. He’s been approached while shopping by a construction work recruiter and told by a graduate adviser in biology to “stop talking like a Puerto Rican.”

Efra Rivera-Serrano, Ph.D.
He’s a scientist at UNC—and also a personal trainer.
Photo from @NakedCapsid Twitter

And the worst part is that he’s far from being the only one in this kind of position. That’s why Rivera-Serrano holds one simple question close to heart:

What would a cell do?

“I use this question to shape the way I tackle problems,” Rivera-Serrano says. After all, a key component of virology is the importance of intercellular communication in controlling disease spread. Similarly, a major goal of diversity-related science communication is “priming” others to fight stereotypes and biases about who belongs in science.

Virology’s “herd immunity” theory operates under the principle that higher vaccination rates mean fewer infections. For some viruses, a 90% vaccination rate is all it takes to completely eradicate an infection from existing in a population. Rivera-Serrano, therefore, hopes to use inclusive science communication as a vaccination tool of sorts to combat discriminatory practices and ideologies in science. He isn’t looking for 100% of the world to agree with him—only enough to make it work.

Herd immunity places value on community rather than individuals.
Image by Tkarcher via Wikimedia Commons

This desire for “inclusive science communication” led Rivera-Serrano to found Unique Scientists, a website that showcases and celebrates diverse scientists from across the globe. Scientists from underrepresented backgrounds can submit a biography and photo to the site and have them published for the world’s aspiring scientists to see.

Some Unique Scientists featured on Rivera-Serrano’s site!

Generating social herd immunity needs to start from an early age, and Unique Scientists has proven itself useful for this purpose. Before introducing the website, school teachers asked their students to draw a scientist. “It’s usually a man who’s white with crazy hair,” according to Rivera-Serrano. Then, they were given the same instructions after browsing through the site, and the results were remarkable.

“Having kids understand pronouns or see an African American in ecology—that’s all something you can do,” Rivera-Serrano explains. It doesn’t take an insane amount of effort to tackle this virus.

What it does take, though, is cooperation. “It’s not a one-person job, for sure,” Rivera-Serrano says. But maybe we can get there together.

by Irene Park

For Lemurs, Water Holes Are a Matter of Taste

It’s 1 PM and you’re only halfway through a 6-hour hike, climbing in steep terrain under a 100° cloudless sky. Your water bottle is nearly empty, and you’ve heard the worst of this hike is yet to come.

And then, just as you are making peace with the fact that you may collapse from dehydration at any second, you approach a small river. The germaphobe side of your brain is shouting for you not to drink from that. The dehydrated animal in you, however, is seriously considering it.

What do you do?

That is the question that Dr. Caroline Amoroso and her collaborators from Duke’s department of evolutionary anthropology, set out to answer. With a slight difference: rather than unprepared hikers, they asked that question to red-fronted lemurs in Madagascar.

Although we often associate Madagascar with lush forests, some regions have a very marked dry season during which water becomes a limited resource. Water holes are few and far apart.

A red-fronted lemur in Kirindy Forest, Madagascar, tanks up at a watering hole. (Photo: Caroline Amoroso)

“On my first visit to Kirindy forest I was amazed at how these waterholes – which are essentially just puddles of standing water – serve as a source of life for so many animals,” says Amoroso.

However, with animals, comes poop. Throughout the season, these water holes quickly become contaminated with fecal matter from all the mammals, birds and reptiles that come have a drink. Amoroso says that fecal contamination was easily detectable even to human observers. “Approaching some waterholes I could tell that lemurs had been there recently because their droppings left such a smell!”

By experimentally manipulating water quality, following groups of radio-collared lemurs and observing lemur behavior at natural water holes, Amoroso and her team found that, all else being equal, lemurs prefer to drink clean water.

Indeed, when offered the choice between a bucket of clean water and a bucket of water containing lemur feces that had been disinfected by boiling, to kill all possible pathogens, lemurs virtually always drank from the clean water bucket. When the buckets were removed and lemurs had to go visit natural water holes, however, they prioritized water holes closer to their resting site, even if they were more contaminated than further ones. Proximity was more important than cleanliness, but if multiple water holes were at similar distances, then lemurs seem to choose the least-contaminated source.

“I was surprised to find evidence that the lemurs chose natural waterholes with lower levels of fecal contamination,” says Amoroso. “I thought that [in a natural setting] avoidance of fecal contamination would be relatively low on the lemurs’ list of priorities.”

After some watchful waiting for predators, and a discussion perhaps, a quartet of Kirindy lemurs visits a tiny watering hole. (Photo: Caroline Amoroso)

The authors highlight that many other factors can influence a lemur’s choice of water hole, such as exposure to potential predators or visits by competing groups. Indeed, Amoroso says that drinking water can be a very risky business for lemurs: “Lemurs would spend upwards of thirty minutes scanning the vegetation nervously and making sure there was no sign of predators before approaching the waterhole and drinking.”

Lemurs prefer clean water, unless it’s too much trouble. In that hike you were on? Lemurs would definitely drink from the river.

Guest Post by Marie Claire Chelini, a postdoctoral fellow in evolutionary anthropology.

The evolution of a tumor

The results of evolution are often awe-inspiring — from the long neck of the giraffe to the majestic colors of a peacock — but evolution does not always create structures of function and beauty.

In the case of cancer, the growth of a population of malignant cells from a single cell reflects a process of evolution too, but with much more harrowing results.

Johannes Reiter uses mathematical models to understand the evolution of cancer

Researchers like Johannes Reiter, PhD, of Stanford University’s Translational Cancer Evolution Laboratory, are examining the path of cancer from a single sell to many metastatic tumors. By using this perspective and simple mathematical models, Reiter interrogates the current practices in cancer treatment. He spoke at Duke’s mathematical biology seminar on Jan. 17.

 The evolutionary process of cancer begins with a single cell. At each division, a cell acquires a few mutations to its genetic code, most of which are inconsequential. However, if the mutations occur in certain genes called driver genes, the cell lineage can follow a different path of rapid growth. If these mutations can survive, cells continue to divide at a rate faster than normal, and the result is a tumor.

As cells divide, they acquire mutations that can drive abnormal growth and form tumors. Tumors and their metastases can consist of diverse cell populations, complicating treatment plans out patient outcomes. Image courtesy of Reiter Lab

With each additional division, the cell continues to acquire mutations. The result is that a single tumor can consist of a variety of unique cell populations; this diversity is called intratumoral heterogeneity (ITH). As tumors metastasize, or spread to other locations throughout the body, the possibility for diversity grows.

Intratumoral heterogeneity can exist within primary tumors, within metastases, or between metastases. Vogelstein et al., Science, 2013

Reiter describes three flavors of ITH. Intra-primary heterogeneity describes the diversity of cell types within the initial tumor. Intrametastatic heterogeneity describes the diversity of cell types within a single metastasis. Finally, inter-metastatic heterogeneity describes diversity between metastases from the same primary tumor.

For Reiter, inter-metastatic heterogeneity presents a particularly compelling problem. If treatment plans are made based on biopsy of the primary tumor but the metastases differ from each other and from the primary tumor, the efficacy of treatment will be greatly limited.

With this in mind, Reiter developed a mathematical model to predict whether a cell sample collected by biopsy of just the primary tumor would provide adequate information for treatment.

Using genetic sequence data from patients who had at least two untreated metastases and a primary tumor, Reiter found that metastases and primary tumors overwhelmingly share a single driver gene. Reiter said this confirmed that a biopsy of the primary tumor should be sufficient to plan targeted therapies, because the risk of missing driver genes that are functional in the metastases proved to be negligible.

 In his next endeavors as a new member of the Canary Center for Cancer Early Detection, Reiter plans to use his knack for mathematical modeling to tackle problems of identifying cancer while still in its most treatable stage.  

Post by undergraduate blogger Sarah Haurin

Post by Sarah Haurin

Flu No More: The Search for a Universal Vaccine

Chances are, you’ve had the flu. 

Body aches, chills, congestion, and cough—for millions across the globe, these symptoms are all too familiar.

For some, though, the flu leads to serious complications. Last year, as many as 647,000 Americans were hospitalized due to flu-related illness, with an additional 61,000 deaths.

Countless hours of lost productivity also accompany the illness. Including hospitalization costs, estimates for the flu’s total economic burden range from 10 to 25 billion dollars each year.

Flu prevention efforts have yielded mixed results. For many viruses, vaccines provide protection that lasts a lifetime, building up a network of antibodies primed to neutralize future infections. Influenza viruses, however, mutate quickly, rendering vaccines from years past ineffective. As a result, new vaccines are constantly in development. 

Every year, researchers predict which flu viruses are likely to dominate the upcoming flu season. Based on these predictions, new vaccines target these specific strains. Consequentially, the effectiveness of these vaccines vary with the prediction. When a vaccine is a good match for the dominant flu strain, it can lower rates of infection by 40-50%. When it isn’t, its preventative power is far lower; in 2014, for example, the yearly influenza vaccine was only 19% effective

Peter Palese, Ph. D, might have a better solution. Working at the Icahn School of Medicine, Palese and his team are developing a vaccine that takes a new approach to flu prevention. 

Just before classes ended last month, Palese spoke at the Duke Influenza Symposium, a showcase of Duke’s current research on influenza. The symposium is part of Duke’s larger push to improve the efficacy of flu vaccination.

Palese’s vaccines work by redirecting the immune response to the influenza virus. Traditional vaccines create antibodies that target hemagglutinins, proteins found on the outermost part of influenza viruses. Hemagglutinins are divided into two regions: a head domain and a stalk domain (Fig. 1).

Fig. 1: Left: General influenza structure. Right: Hemagglutinins are divided into two regions: a head domain and a stalk. The head domain is prone to mutation and undergoes rapid change while the stalk domain is more resistant to mutation.
Source: Frontiers in Immunology

In a traditional vaccination, the head domain is immunodominant—that is, the antibodies produced by vaccines preferentially target and neutralize the head domains. However, the head domain is highly prone to mutation and varies between different strains of influenza. As a result, antibodies for one strain of the virus provide no protection against other strains.

The new vaccines pioneered by Palese and his team instead target the stalk domain, a part of hemagglutinin that mutates far slower than the head domain. The stalk is also conserved across different subtypes of the influenza virus. As a result, these vaccines should theoretically provide long-lasting protection against most strains of influenza.

Testing in ferret, mice, and guinea pigs have produced promising results. And early human trials suggest that this new kind of vaccination grants broad immunity against influenza. But long-term results remain unclear—and more trials are underway. “We would love to say it works,” Palese says. “But give us 10 years.”

In the meantime, the seasonal flu vaccine is our best option.“The recommendation to vaccinate everyone is the right policy,” Palese tells us.

Post by Jeremy Jacobs

Working Through Frustrations to Understand Nature Better

This is the fifth of six posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Research is a journey full of uncertainty in which scientists have to construct their own path, even if they’re unsure of what the end of the journey actually is. Despite this unpredictability, researchers continue their journey because they believe their work will one day drive their fields forward. At least, that’s why Kate Meyer Ph.D. says she has investigated something called m6A for several years.

Kathryn Meyer, Ph.D.

“Virtually every study that I have ever been part of had some frustrations involved because everything can fall apart in just one night,” Meyer said. “Despite all the frustrations you might have, you are still in the research because you know that at the end of the day, you will get new knowledge that is worthy to your field, or perhaps to the world.”

N6-methyladenosine (or m6A) is a modification to one of the four main bases of RNA – adenosine. Because RNA plays a significant role as a bridge between genetic information and functional gene products, modifications in RNA can alter how much of a certain product will be produced, which then controls how our cells and eventually our whole body functions.

The idea of this tiny but powerful modification was first proposed in the 1970s. But scientists struggled to find where m6A was located in the cell before research Meyer made a major contribution to as a trainee was published in 2012. Combining a newly developed antibody that could recognize m6A and gene sequencing techniques that became more accessible to the researchers, Meyer’s work led to the first method that can detect and sequence all of the m6A regions in a cell.

m6A’s interaction with a neuron, as depicted on Dr. Meyer’s laboratory site.

Meyer’s work was transformative research. Her method allowed laboratories around the world to investigate what regulates m6A and what its consequences are. Meyer said this first study which ignited m6A field is one of her most prideful moments as a researcher. 

Significant progress has been made since 2012, but there are still lots of questions that need to be answered. Currently, Meyer’s research team is investigating the relationships between m6A and various neurological issues. She believes that regulation of m6A controls the expression, or activity level, of various genes in the brain. As such, m6A may play an important role in neurodegenerative diseases and memory.

Author Jun Hee Shin, left, and Kate Meyer in her lab.

As an assistant professor of both biochemistry and neurobiology at Duke, Meyer is definitely one of the most important figures in the m6A field. Despite her many accomplishments, she said she had experienced and overcome many frustrations and failures on her way to the results.

Guest Post by Jun Shin, NCSSM 2020

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