This squiggly line shows the path taken by a snippet of DNA as it might move around within the soupy interior of a cell. Duke’s Kevin Welsher and colleagues have developed a technique that turns a microscope into a ‘flight tracker’ for molecules, making it possible to follow the paths of viruses and other particles thousands of times smaller than the period at the end of this sentence. Until now, such techniques have required particles to be tethered to make sure they stay within the field of view. But the Welsher lab has developed a way to lock on to freely moving targets and track them for minutes at a time.
We offered fruit-eating ruffed lemurs at the Duke Lemur Center fresh lettuce each afternoon for 10 days. They happily ate it and their gut microbiomes shifted, suggesting that leafy greens could be incorporated into the lemurs’ standard dietary regimen to boost foraging opportunity and fiber intake.
Red-ruffed lemurs and black-and-white ruffed lemurs are some of Madagascar’s most iconic wildlife. Sporting a long snout and a neck ruff to rival those of the Elizabethan court, these primates naturally live in the rainforests, where they mostly eat fruits and flowers, and make their living as seed dispersers and pollinators.
Ruffed lemurs really like romaine lettuce and their gut bugs do too! (Lydia Greene)
Ruffed lemurs also live in zoos worldwide, where they are given fruit-rich diets to match those foraged by their wild peers. But scientists are starting to realize that the fruit eaten by wild lemurs is quite different from the domesticated fruit provided at zoos. Wild fruits are seedy, pulpy, and thick-skinned, whereas orchard fruits are fleshy, plump, and sweet. From a nutritional standpoint, wild fruits contain more fiber, whereas orchard fruits contain more sugar.
Our team wondered if a fiber boost might benefit Duke’s ruffed lemur colony. But would these fruit-loving lemurs eat their veggies?
Cue the salad bar.
To test this idea, we offered ruffed lemurs at the Duke Lemur Center a lot of lettuce. Lettuce seemed like a pretty palatable way to stimulate foraging behavior, while boosting fiber intake.
With help from the research department, we offered 19 ruffed lemurs 150-200 grams of romaine lettuce each day, which is about double the weight of their standard diet. We repeated this regimen every day for 10 days, while recording the lemurs’ feeding behavior and collecting fecal samples for gut microbiome analysis. Because gut microbes are chiefly responsible for converting plant fiber into energy for the lemurs, measuring changes to the lemurs’ microbiomes offered a way to ‘see’ the impact of lettuce consumption.
It turns out that ruffed lemurs really like lettuce. They consistently ate lettuce every day and showed no decline in consumption across the study. Younger animals ate more lettuce than did geriatric lemurs, but all lemurs spent more time crunching on lettuce stalks than the leaves.
And their gut microbiomes responded. We noted two microbes that were more abundant on the lettuce diet: a known fiber digester from the Ruminococcaceae family, and a microbe known for its positive association with host health in other animals called Akkermansia.
Despite their classification as fruit eaters, ruffed lemurs readily eat lettuce. We think lettuce can be used to extend the lemurs’ foraging time while boosting dietary fiber. And it might just help replicate the lifestyles experienced by wild ruffed lemurs in their native Malagasy rainforests. At the Duke Lemur Center, lettuce is now a routine item offered to ruffed lemurs (and other species too!). Next time you come out for a tour (once it’s safe to do so), you might get to see them crunching away on their new favorite snack!
Like wine, cheese, and savvy financial investments, many tropical trees become more valuable with age. This is particularly true when it comes to carbon storage, because old trees are often the biggest trees and the larger the tree, the more carbon it stores.
The value of big, old trees in combating climate change was underscored in a recent study of Gabon’s forests, led by the Nicholas School of the Environment’s John Poulsen. The team’s striking finding — that half of Gabon’s wealth of carbon is found in the largest 5% of trees — has implications that reach far beyond the sparsely populated Central African country’s borders.
Nicholas School Ph.D. student Graden Froese admires a forest giant in Ivindo National Park, Gabon.
Tropical forests play a key role in the global carbon cycle by keeping carbon out of the atmosphere. Trees take in CO2 — one of the infamous, heat-trapping greenhouse gases — during photosynthesis and use the carbon to grow, making new leaves, thicker and taller trunks, and more expansive root systems.
Scientists can estimate how much carbon a tree holds by measuring its trunk. So, like rainforest tailors, trained technicians traveled to all corners of the country to measure the girth and height of tens of thousands of trees.
This extraordinary two-year long effort was one of the first nationwide forest inventories in the tropics, making Gabon a leader in comprehensive forest monitoring.
John Poulsen is an associate professor of tropical ecology.
Poulsen and collaborators used the tree measurements to estimate the amount of carbon stored in Gabon’s forests and to determine why some forests hold more carbon than others.
“The field techs deserve all the credit”, Poulsen explained, “as they often walked for days through thick forest, traversing swamps and enduring humid, buggy conditions to measure trees. We turned their sweat and toil into information that could be used by Gabon’s government to prioritize areas for conservation.”
Who needs ladders, when you have colleagues? The field team collaborates to measure a forest giant.
The team analyzed a suite of environmental factors to see their effects on carbon storage. Of the natural factors, only soil fertility had a noticeable positive effect on tree biomass. Much more important was the impact of humans. As human activities such as agriculture and logging tend to target large trees, more heavily human-disturbed forests had a much different structure than pristine forests. The farther a study area was from human settlements, the more likely it was to host large trees and consequently, higher amounts of carbon.
The paper notes that Gabon stands out as a country with “one of the highest densities of aboveground forest carbon.” In fact, Gabon’s undisturbed forests store more carbon than those in the Amazon, which have been referred to as the lungs of the planet.
According to Poulsen, “Gabon is the second most forested country in the world with 87% forest cover, a deforestation rate near zero…” Because of its impressive forest cover and its location straddling the equator, Gabon’s forests host an incredibly diverse array of plants and animals, including many threatened and endangered species. Rural communities depend on these forests for their livelihoods.
Unfortunately, even Gabon’s ‘small’ trees make for spectacular felled logs.
However, Gabon’s impressive forests are valuable to more than just wildlife, climate researchers, and local communities. The logging industry also sees these forests as a chance for profit. More than half (about 67%) of Gabon’s forests are under contract with logging companies to harvest timber, putting them at risk of losing many of their carbon-storing giants.
Poulsen’s study highlights the importance of a more nuanced approach to forest conservation in Gabon. One that doesn’t simply focus on stopping deforestation or promoting restoration, as is prescribed in many international climate change plans, but an approach that recognizes the necessity of preserving high conservation value, old growth forests.
Guest Post by Anna Nordseth, a graduate student in the Nicholas School of the Environment.
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
Most of Physics Professor Haiyan Gao’s students see their doctoral dissertations posted on her lab’s web site very soon after they have been awarded their Ph.Ds.
But Yang Zhang, Ph.D. 2018, had to wait two years, because his thesis work had a very good chance of being accepted by a major journal. And this week, it has been published in the journal Science.
What Zhang did was to create the world’s most precise value for a subatomic nuclear particle called a neutral pion. It’s a quark and an antiquark comprising a meson. The neutral pion (also known as p0) is the lightest of the mesons, but a player in the strong attractive force that holds the atom’s nucleus together.
Haiyan Gao (left) with newly-minted physics Ph.D. Yang Zhang in 2018. (Photo courtesy of Min Huang, Ph.D. ’16)
And that, in turn, makes it a part of the puzzle Gao and her students have been trying to solve for many years. The prevailing theory about the strong force is called quantum chromodynamics (QCD), and it’s been probed for years by high-energy physics. But Gao, Zhang and their collaborators are trying to study QCD under more normal energy states, a notoriously difficult problem.
Yang Zhang spent six years analyzing and writing up the data from a Primakoff (PrimEx-II) experiment in Hall B at Thomas Jefferson National Accelerator Facility (Jefferson Lab) in Newport News, VA. His work was done on equipment supported by both the National Science Foundation and the Department of Energy.
This is the quark structure of the positive pion – an up quark and an anti-down quark. The strong force is from gluons, represented as the wavy lines (Arpad Horvath via Wikimedia Commons)
In a Primakoff experiment, a photon beam is directed on a nuclear target, producing neutral pions. In both the PrimEx-I and PrimEx-II experiments at Jefferson Lab, the two photons from the decay of a neutral pionwere subsequently detected in an electromagnetic calorimeter. From that, Zhang extracted the pion’s ‘radiative decay width.’ That decay width is a handy thing to have, because it is directly related to the pion’s life expectancy, and QCD has a direct prediction for it.
Zhang’s hard-won answer: The neutral pion has a radiative decay width of 7.8 electron-volts, give or take. That makes it an important piece of the dauntingly huge puzzle about QCD. Gao and her colleagues will continue to ask the fundamental questions about nature, at the finest but perhaps most profound scale imaginable.
The PrimEx-I and PrimEx-II collaborations were led by Prof. Ashot Gasparian from North Carolina A&T State University. Gao and Zhang joined the collaboration in 2011.
“Precision Measurement of the Neutral Pion Lifetime,” appears in Science May 1. Dr. Yang Zhang is now a quantitative researcher at JPMorgan Chase & Co.
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)
Many university labs may have gone quiet amid coronavirus shutdowns, but faculty continue to analyze data, publish papers and write grants. In this guest post from Duke chemistry professor David Beratan and colleagues, the researchers describe a new study showing how water’s ability to shepherd electrons can change with subtle shifts in a water molecule’s 3-D structure:
Water, the humble combination of hydrogen and oxygen, is essential for life. Despite its central place in nature, relatively little is known about the role that single water molecules play in biology.
Researchers at Duke University, in collaboration with Arizona State University, Pennsylvania State University and University of California-Davis have studied how electrons flow though water molecules, a process crucial for the energy-generating machinery of living systems. The team discovered that the way that water molecules cluster on solid surfaces enables the molecules to be either strong or weak mediators of electron transfer, depending on their orientation. The team’s experiments show that water is able to adopt a higher- or a lower-conducting form, much like the electrical switch on your wall. They were able to shift between the two structures using large electric fields.
In a previous paper published fifteen years ago in the journal Science, Duke chemistry professor David Beratan predicted that water’s mediation properties in living systems would depend on how the water molecules are oriented.
Water assemblies and chains occur throughout biological systems. “If you know the conducting properties of the two forms for a single water molecule, then you can predict the conducting properties of a water chain,” said Limin Xiang, a postdoctoral scholar at University of California, Berkeley, and the first author of the paper.
“Just like the piling up of Lego bricks, you could also pile up a water chain with the two forms of water as the building blocks,” Xiang said.
In addition to discovering the two forms of water, the authors also found that water can change its structure at high voltages. Indeed, when the voltage is large, water switches from a high- to a low-conductive form. In fact, it is may be possible that this switching could gate the flow of electron charge in living systems.
This study marks an important first step in establishing water synthetic structures that could assist in making electrical contact between biomolecules and electrodes. In addition, the research may help reveal nature’s strategies for maintaining appropriate electron transport through water molecules and could shed light on diseases linked to oxidative damage processes.
The researchers dedicate this study to the memory of Prof. Nongjian (NJ) Tao.
The COVID-19 epidemic has impacted the Duke research enterprise in profound ways. Nearly all laboratory-based research has been temporarily halted, except for research directly connected to the fight against COVID-19. It will take much time to return to normal, and that process of renewal will be gradual and will be implemented carefully.
Trying to put this situation into a broader perspective, I thought of the 1939 essay by Abraham Flexner published in Harper’s magazine, entitled “The Usefulness of Useless Knowledge.” Flexner was the founding Director of the Institute for Advanced Study at Princeton, and in that essay, he ruminated on much of the type of knowledge acquired at research universities — knowledge motivated by no objective other than the basic human desire to understand. As Flexner said, the pursuit of this type of knowledge sometimes leads to surprises that transform the way we see that which was previously taken for granted, or for which we had previously given up hope. Such knowledge is sometimes very useful, in highly unintended ways.
Gregory Gray, MD MPH
The 1918 influenza pandemic led to 500 million confirmed cases, and 50 million deaths. In the Century since, consider how far we have come in our understanding of epidemics, and how that knowledge has impacted our ability to respond. People like Greg Gray, a professor of medicine and member of the Duke Global Health Institute (DGHI), have been quietly studying viruses for many years, including how viruses at domestic animal farms and food markets can leap from animals to humans. Many believe the COVID-19 virus started from a bat and was transferred to a human. Dr. Gray has been a global leader in studying this mechanism of a potential viral pandemic, doing much of his work in Asia, and that experience makes him uniquely positioned to provide understanding of our current predicament.
From the health-policy perspective, Mark McClellan, Director of the Duke Margolis Center for Health Policy, has been a leading voice in understanding viruses and the best policy responses to an epidemic. As a former FDA director, he has experience bringing policy to life, and his voice carries weight in the halls of Washington. Drawing on faculty from across Duke and its extensive applied policy research capacity, the Margolis Center has been at the forefront in guiding policymakers in responding to COVID-19.
Through knowledge accrued by academic leaders like Drs. Gray and McClellan, one notes with awe the difference in how the world has responded to a viral threat today, relative to 100 years ago. While there has been significant turmoil in many people’s lives today, as well as significant hardship, the number of global deaths caused by COVID-19 has been reduced substantially relative to 1918.
One of the seemingly unusual aspects of COVID-19 is that a substantial fraction of the population infected by the virus has no symptoms. However, those asymptomatic individuals shed the virus and infect others. While most people have no or mild symptoms, other people have very adverse effects to COVID-19, some dying quickly.
This heterogeneous response to COVID-19 is a characteristic of viruses studied by Chris Woods, a professor medicine in infectious diseases. Dr. Woods, and his colleagues in the Schools of Medicine and Engineering, have investigated this phenomenon for years, long before the current crisis, focusing their studies on the genomic response of the human host to a virus. This knowledge of viruses has made Dr. Woods and his colleagues leading voices in understanding COVID-19, and guiding the clinical response.
A team led by Greg Sempowski, a professor of pathology in the Human Vaccine Institute is working to isolate protective antibodies from SARS-CoV-2-infected individuals to see if they may be used as drugs to prevent or treat COVID-19. They’re seeking antibodies that can neutralize or kill the virus, which are called neutralizing antibodies.
Barton Haynes, MD
Many believe that only a vaccine for COVID-19 can truly return life to normal. Human Vaccine Institute Director Barton Haynes, and his colleagues are at the forefront of developing that vaccine to provide human resistance to COVID-19. Dr. Haynes has been focusing on vaccine research for numerous years, and now that work is at the forefront in the fight against COVID-19.
Engineering and materials science have also advanced significantly since 1918. Ken Gall, a professor of mechanical engineering and materials science has led Duke’s novel application of 3D printing to develop methods for creatively designing personal protective equipment (PPE). These PPE are being used in the Duke hospital, and throughout the world to protect healthcare providers in the fight against COVID-19.
Much of the work discussed above, in addition to being motivated by the desire to understand and adapt to viruses, is motivated from the perspective that viruses must be fought to extend human life.
In contrast, several years ago Jennifer Doudna and Emmanuelle Charpentier, academics at Berkeley and the Max Planck Institute, respectively, asked a seemingly useless question. They wanted to understand how bacteria defended themselves against a virus. What may have made this work seem even more useless is that the specific class of viruses (called phage) that infect bacteria do not cause human disease. Useless stuff! The kind of work that can only take place at a university. That basic research led to the discovery of clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial defense system against viruses, as a tool for manipulating genome sequences. Unexpectedly, CRISPR manifested an almost unbelievable ability to edit the genome, with the potential to cure previously incurable genetic diseases.
Charles Gersbach, a professor of Biomedical Engineering, and his colleagues at Duke are at the forefront of CRISPR research for gene and cell therapy. In fact, he is working with Duke surgery professor and gene therapy expert Aravind Asokan to engineer another class of viruses, recently approved by the FDA for other gene therapies, to deliver CRISPR to diseased tissues. Far from a killer, the modified virus is essential to getting CRISPR to the right tissues to perform gene editing in a manner that was previously thought impossible. There is hope that CRISPR technology can lead to cures for sickle cell and other genetic blood disorders. It is also being used to fight cancer and muscular dystrophy, among many other diseases and it is being used at Duke by Dr. Gersbach in the fight against COVID-19.
David Ashley, Ph.D.
In another seemingly bizarre use of a virus, a modified form of the polio virus is being used at Duke to fight glioblastoma, a brain tumor. That work is being pursued within the Preston Robert Tisch Brain Tumor Center, for which David Ashley is the Director. The use of modified polio virus excites the innate human immune system to fight glioblastoma, and extends life in ways that were previously unimaginable. But there are still many basic-science questions that must be overcome. The remarkable extension of life with polio-based immunotherapy occurs for only 20% of glioblastoma patients. Why? Recall from the work of Dr. Woods discussed above, and from our own observation of COVID-19, not all people respond to viruses in the same way. Could this explain the mixed effectiveness of immunotherapy for glioblastoma? It is not known at this time, although Dr. Ashley feels it is likely to be a key factor. Much research is required, to better understand the diversity in the host response to viruses, and to further improve immunotherapy.
The COVID-19 pandemic is a challenge that is disrupting all aspects of life. Through fundamental research being done at Duke, our understanding of such a pandemic has advanced markedly, speeding and improving our capacity to respond. By innovative partnerships between Duke engineers and clinicians, novel methods are being developed to protect frontline medical professionals. Further, via innovative technologies like CRISPR and immunotherapy — that could only seem like science fiction in 1918 (and as recently as 2010!) — viruses are being used to save lives for previously intractable diseases.
Viruses can be killers, but they are also scientific marvels. This is the promise of fundamental research; this is the impact of Duke research.
“We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know the place for the first time.”
T.S. Eliot, Four Quartets
Post by Lawrence Carin, Vice President for Research
Martin Brooke is no
ordinary Engineering professor at Duke University. He teaches computer scientists,
engineers, and technology nerds how to dance.
Brooke co-teaches Performance and Technology, an interactive course where students create performance projects and discuss theoretical and historical implications of technologies in performance. In a unique partnership with Thomas DeFrantz, a professor of African and African American Studies and Dance students will design a technology based on “heart,” for example, in order to understand how human expression is embedded in technology. Two weeks later, they’ll interact with motion-sensing, robotic trees that give hugs; and 3D printed hearts that detect colors and match people, sort of like a robotic tinder.
Thomas DeFrantz (left) and Martin Brooke watch their students perform in the Performance and Technology course .
Brooke loves that this class is fun and interactive, but more importantly he loves that this class teaches students how to consider people’s emotions, facial expressions, cultural differences, cultural similarities and interactions when designing new technologies.
Human interface is when a computerized program or device
takes input from humans — like an image of a face — and gives an output — like
unlocking a phone. In order for these devices to understand human interface,
the programmer must first understand how humans express themselves. This means
that scientists, programmers, and engineers need to understand a particular
school of learning: the humanities. “There are very, very few scientists who do human interface research,” Brooke
said.
The students designed a robotic “Tinder” that changes colors when it detects a match.
Brooke also mentioned the
importance of understanding human expressions and interactions in order to
limit computer bias. Computer bias occurs when a programmer’s prejudiced
opinions of others are transferred into the computer products they design. For
example, many recent studies have proven that facial recognition software
inaccurately identifies black individuals when searching for suspects of a
criminal case.
“It turns out one of the biggest problems with technology today is human interface,” Brooke said. “Microsoft found out that they had a motion sensitive Artificial Intelligence that tended to say women, [more often than men], were angry.” Brooke said he didn’t consider the importance of incorporating the arts and humanities into engineering before coming to Duke. He suggested that it can be uncomfortable for some scientists to think and express themselves artistically. “[When] technologists [take Performance and Technology], for example, they are terrified of the performance aspects of it. We have some video of a guy saying, ‘I didn’t realize I was going to have to perform.’ Yeah, that’s what we were actually quite worried about, but in the end, he’s there in the video, doing slow motion running on stage — fully involved, actually performing, and really enjoying it.
Duke has a strong initiative to promote arts and humanities inclusion in science, technology, engineering, and mathematics. Brooke plans to bring Bass Connections, a research program that focuses on public outreach and cross-disciplinary work, to his Performance and Technology class before the end of the semester to demonstrate bias through a program he callsAI Bias In the Age of a Technical Elite.
“You give it someone’s name and it will come up with a
movie title, their role, and a synopsis of the movie,” Brooke said. “When I put
in my name, which is an English name, it said that the movie I would be in is
about a little boy who lives in the English countryside who turns into a
monster and terrorizes the town.” This program shows even something as
simple as a name can have so much stigma attached to it.
Bass Connections Students working on technology and engineering projects. (From the official Duke page for Bass Connections.)
Brooke’s hope is that his class teaches students to think about technology and human interface. “Hopefully that’s a real benefit to them when they get out actually designing products.”
Guest post by Jordan Anderson, a masters student in Science & Society
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.”
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.
