What are the trials and tribulations one can expect? And conversely, what are the highlights? To answer these questions, Duke Research & Innovation Week kicked off with a panel discussion on Monday, January 23.
The panel
Moderated by George A. Truskey, Ph.D, the Associate Vice President for Research & Innovation and a professor in the Department of Biomedical Engineering, the panelists included…
Claudia K. Gunsch, Ph.D., a professor in the Departments of Civil & Environmental Engineering, Biomedical Engineering, and Environmental Science & Policy. Dr. Gunsch is the director of the NSF Engineering Research Center for Microbiome Engineering (PreMiEr) and is also the Associate Dean for Duke Engineering Research & Infrastructure.
Dr. Claudia Gunsch
Yiran Chen, Ph.D., a professor in the Department of Electrical & Computer Engineering. Dr. Chen is the director of the NSF AI Institute for Edge Computing (Athena).
Dr. Yiran Chen
Stephen Craig, Ph.D., a professor in the Department of Chemistry. Dr. Craig is the director of the Center for the Chemistry of Molecularly Optimized Networks (MONET).
Dr. Stephen Craig
The centers
As the panelists joked, a catchy acronym for a research center is almost an unspoken requirement. Case in point: PreMiEr, Athena, and MONET were the centers discussed on Monday. As evidenced by the diversity of research explored by the three centers, large externally-funded centers run the gamut of academic fields.
PreMiEr, which is led by Gunsch, is looking to answer the question of microbiome acquisition. Globally, inflammatory diseases are connected to the microbiome, and studies suggest that our built environment is the problem, given that Americans spend on average less than 8% of time outdoors. It’s atypical for an Engineering Research Center (ERC) to be concentrated in one state but uniquely, PreMieR is. The center is a joint venture between Duke University, North Carolina A&T State University, North Carolina State University, the University of North Carolina – Chapel Hill and the University of North Carolina – Charlotte.
PreMiEr – not to be confused with the English Premier League
Dr. Chen’s Athena is the first funded AI institute for edge computing. Edge computing is all about improving a computer’s ability to process data faster and at greater volumes by processing data closer to where it’s being generated. AI is a relatively new branch of research, but it is growing in prevalence and in funding. In 2020, 7 institutes looking at AI were funded by the National Science Foundation (NSF), with total funding equaling 140 million. By 2021, 11 institutes were funded at 220 million – including Athena. All of these institutes span over 48 U.S states.
Athena, or the Greek goddess of wisdom, is a fitting name for a research center
MONET is innovating in polymer chemistry with Stephen Craig leading. Conceptualizing polymers as operating in a network, the center aims to connect the behaviors of a single chemical molecule in that network to the behavior of the network as a whole. The goal of the center is to transform polymer and materials chemistry by “developing the knowledge and methods to enable molecular-level, chemical control of polymer network properties for the betterment of humankind.” The center has nine partner institutions in the U.S and one internationally.
MONET, like French painter Claude Monet
Key takeaways
Research that matters
Dr. Gunsch talked at length about how PreMiEr aspires to pursue convergent research. She describes this as identifying a large, societal challenge, then determining what individual fields can “converge” to solve the problem.
Because these centers aspire to solve large, societal problems, market research and industry involvement is common and often required in the form of an industry advisory group. At PreMiEr, the advisory group performs market analyses to assess the relevance and importance of their research. Dr. Chen also remarked that there is an advisory group at Athena, and in addition to academic institutions the center also boasts collaborators in the form of companies like Microsoft, Motorola, and AT&T.
Dr. Chen presenting on Athena’s partner institutions at Monday’s talk.
Commonalities in structure
Most research centers, like PreMiEr, Athena, and MONET, organize their work around pillars or “thrusts.” This can help to make research goals understandable to a lay audience but also clarifies the purpose of these centers to the NSF, other funding bodies, host and collaborating institutions, and the researchers themselves.
How exactly these goals are organized and presented is up to the center in question. For example, MONET conceptualizes its vision into three fronts – “fundamental chemical advances,” “conceptual advances,” and “technological advances.”
At Athena, the research is organized into four “thrusts” – “AI for Edge Computing,” “AI-Powered Computer Systems,” “AI-Powered Networking Systems,” and “AI-Enabled Services and Applications.”
Meanwhile, at PreMiEr, the three “thrusts” have a more procedural slant. The first “thrust” is “Measure,” involving the development of tracking tools and the exploration of microbial “dark matter.” Then there’s “Modify,” or the modification of target delivery methods based on measurements. Finally, “Modeling” involves predictive microbiome monitoring to generate models that can help analyze built environment microbiomes.
A center is about the people
“Collaborators who change what you can do are a gift. Collaborators who change how you think are a blessing.”
Dr. stephen craig
All three panelists emphasized that their centers would be nowhere without the people that make the work possible. But of course, humans complicate every equation, and when working with a team, it is important to anticipate and address tensions that may arise.
Dr. Craig spoke to the fact that successful people are also busy people, so what may be one person’s highest priority may not necessarily be another person’s priority. This makes it important to assemble a team of researchers that are united in a common vision. But, if you choose wisely, it’s worth it. As Dr. Craig quipped on one of his slides, “Collaborators who change what you can do are a gift. Collaborators who change how you think are a blessing.”
In academia, there is a loud push for diversity, and research centers are no exception. Dr. Chen spoke about Athena’s goals to continue to increase their proportions of female and underrepresented minority (URM) researchers. At PreMiEr, comprised of 42 scholars, the ratio of non-URM to URM researchers is 83-17, and the ratio of male to female researchers is approximately 50-50.
In conclusion, cutting-edge research is often equal parts thrilling and mundane, as the realities of applying for funding, organizing manpower, pushing through failures, and working out tensions with others sets in. But the opportunity to receive funding in order to start and run an externally-funded center is the chance to put together some of the brightest minds to solve some of the most pressing problems the world faces. And this imperative is summarized well by the words of Dr. Craig: “Remember: if you get it, you have to do it!”
It’s not enough to just publish a great scientific paper.
Somebody else has to think it’s great too and include the work in the references at the end of their paper, the citations. The more citations a paper gets, presumably the more important and influential it is. That’s how science works — you know, the whole standing-on-the-shoulders-of-giants thing.
So it always comes as a chest swelling affirmation for Dukies when we read all those Duke names on the annual list of Most Cited Scientists, compiled by the folks at Clarivate.
This year is another great haul for our thought-leaders. Duke has 30 scientists among the nearly 7,000 authors on the global list, meaning their work is among the top 1 percent of citations by scientific field and year, according to Clarivate’s Web of Science citation index.
As befits Duke’s culture of mixing and matching the sciences in bold new ways, most of the highly cited are from “cross-field” work.
Duke’s Most Cited Are:
Biology and Biochemistry
Charles A. Gersbach
Robert J. Lefkowitz
Clinical Medicine
Scott Antonia
Christopher Bull Granger
Pamela S. Douglas
Adrian F. Hernandez
Manesh R. Patel
Eric D. Peterson
Cross-Field
Chris Beyrer
Stefano Curtarolo
Renate Houts
Tony Jun Huang
Ru-Rong Ji
Jie Liu
Jason Locasale
Edward A. Miao
David B. Mitzi
Christopher B. Newgard
John F. Rawls
Drew T. Shindell
Pratiksha I. Thakore
Mark R. Wiesner
Microbiology
Barton F. Haynes
Neuroscience and Behavior
Quinn T. Ostrom
Pharmacology and Toxicology
Evan D. Kharasch
Plant and Animal Science
Xinnian Dong
Sheng Yang He
Psychiatry and Psychology
Avshalom Caspi
William E. Copeland
E. Jane Costello
Terrie E. Moffitt
Social Sciences
Michael J. Pencina
John W. Williams
Congratulations, one and all! You’ve done us proud again.
Saxicolous lichens (lichens that grow on stones) from the Namib Desert, and finger lichen, Dactylina arctica (bottom left insert), common in the Arctic, on display in Dr. Jolanta Miadlikowska’s office. The orange color on some of the lichen comes from metabolites, or secondary chemicals produced by different lichen species. The finger lichen is hollow.
Lichens are everywhere—grayish-green patches on tree bark on the Duke campus, rough orange crusts on desert rocks, even in the Antarctic tundra. They are “pioneer species,” often the first living things to return to barren, desolate places after an extreme disturbance like a lava flow. They can withstand extreme conditions and survive where nearly nothing else can. But what exactly are lichens, and why does Duke have 160,000 of them in little envelopes? I reached out to Dr. Jolanta Miadlikowska and Dr. Scott LaGreca, two lichen researchers at Duke, to learn more.
Dr. Jolanta Miadlikowska looking at lichen specimens under a dissecting microscope. The pale, stringy lichen on the brown bag is whiteworm lichen (Thamnolia vermicularis), used to make “snow tea” in parts of China.
According to Miadlikowska, a senior researcher, lab manager, and lichenologist in the Lutzoni Lab (and one of the Instructors B for the Bio201 Gateway course) at Duke, lichens are “obligate symbiotic associations,” meaning they are composed of two or more organisms that need each other. All lichens represent a symbiotic relationship between a fungus (the “mycobiont”) and either an alga or a cyanobacterium or both (the “photobiont”). They aren’t just cohabiting; they rely on each other for survival. The mycobiont builds the thallus, which gives lichen its structure. The photobiont, on the other hand, isn’t visible—but it is important: it provides “food” for the lichen and can sometimes affect the lichen’s color. The name of a lichen species refers to its fungal partner, whereas the photobiont has its own name.
Lichen viewed through a dissecting microscope. The black speckles visible on some of the orange lichen lobes are a “lichenicolous” fungus that can grow on top of lichen. There are also “endolichenic fungi… very complex fungal communities that live inside lichen,” Miadlikowska says. “We don’t see them, but they are there. And they are very interesting.”
Unlike plants, fungi can’t perform photosynthesis, so they have to find other ways to feed themselves. Many fungi, like mushrooms and bread mold, are saprotrophs, meaning they get nutrients from organic matter in their environment. (The word “saprotroph” comes from Greek and literally means “rotten nourishment.”) But the fungi in lichens, Miadlikowska says, “found another way of getting the sugar—because it’s all about the sugar—by associating with an organism that can do photosynthesis.” More often than not, that organism is a type of green algae, but it can also be a photosynthetic bacterium (cyanobacteria, also called blue-green algae). It is still unclear how the mycobiont finds the matching photobiont if both partners are not dispersed together. Maybe the fungal spores (very small fungal reproductive unit) “will just sit and wait” until the right photobiont partner comes along. (How romantic.) Some mycobionts are specialists that “can only associate with a few or a single partner—a ‘species’ of Nostoc [a cyanobacterium; we still don’t know how many species of symbiotic and free-living Nostoc are out there and how to recognize them], for example,” but many are generalists with more flexible preferences.
Two species of foliose (leaf-like) lichens from the genus Peltigera. In the species on the left (P. canina), the only photobiont is a cyanobacterium from the genus Nostoc, making it an example of bi-membered symbiosis. In the species on the right (P.aphthosa), on the other hand, the primary photobiont is a green alga (which is why the thallus is so green when wet). In this case, Nostoc is a secondary photobiont contained only in the cephalodia—the dark, wart-like structures on the surface. With two photobionts plus the mycobiont, this is an example of tri-membered symbiosis.
Lichens are classified based on their overall thallus shape. They can be foliose (leaf-like), fruticose (shrubby), or crustose (forming a crust on rocks or other surfaces). Lichens that grow on trees are epiphytic, while those that live on rocks are saxicolous; lichens that live on top of mosses are muscicolous, and ground-dwelling lichens are terricolous. Much of Miadlikowska’s research is on a group of cyanolichens (lichens with cyanobacteria partners) from the genus Peltigera. She works on the systematics and evolution of this group using morphology-, anatomy-, and chemistry-based methods and molecular phylogenetic tools. She is also part of a team exploring biodiversity, ecological rules, and biogeographical patterns in cryptic fungal communities associated with lichens and plants (endolichenic and endophytic fungi). She has been involved in multiple ongoing NSF-funded projects and also helping graduate students Ian, Carlos, Shannon, and Diego in their dissertation research. She spent last summer collecting lichens with Carlos and Shannon and collaborators in Alberta, Canada and Alaska. If you walk in the sub basement of the Bio Sciences building where Bio201 and Bio202 labs are located, check out the amazing photos of lichens (taken by Thomas Barlow, former Duke undergraduate) displayed along the walls! Notice Peltigera species, including some new to science, described by the Duke lichen team.
Lichens have value beyond the realm of research, too. “In traditional medicine, lichens have a lot of use,” Miadlikowska says. Aside from medicinal uses, they have also been used to dye fabric and kill wolves. Some are edible. Miadlikowska herself has eaten them several times. She had salad in China that was made with leafy lichens (the taste, she says, came mostly from soy sauce and rice vinegar, but “the texture was coming from the lichen.”). In Quebec, she drank tea made with native plants and lichens, and in Scandinavia, she tried candied Cetraria islandica lichen (she mostly tasted the sugar and a bit of bitterness, but once again, the lichen’s texture was apparent).
In today’s changing world, lichens have another use as well, as “bioindicators to monitor the quality of the air.” Most lichens can’t tolerate air pollution, which is why “in big cities… when you look at the trees, there are almost no lichens. The bark is just naked.” Lichen-covered trees, then, can be a very good sign, though the type of lichen matters, too. “The most sensitive lichens are the shrubby ones… like Usnea,” Miadlikowska says. Some lichens, on the other hand, “are able to survive in anthropogenic places, and they just take over.” Even on “artificial substrates like concrete, you often see lichens.” Along with being very sensitive to poor air quality, lichens also accumulate pollutants, which makes them useful for monitoring deposition of metals and radioactive materials in the environment.
Dr. Scott LaGreca with some of the 160,000 lichen specimens in Duke’s herbarium.
LaGreca, like Miadlikoska, is a lichenologist. His research primarily concerns systematics, evolution and chemistry of the genus Ramalina. He’s particularly interested in “species-level relationships.” While he specializes in lichens now, LaGreca was a botany major in college. He’d always been interested in plants, in part because they’re so different from animals—a whole different “way of being,” as he puts it. He used to take himself on botany walks in high school, and he never lost his passion for learning the names of different species. “Everything has a name,” he says. “Everything out there has a name.” Those names aren’t always well-known. “Some people are plant-blind, as they call it…. They don’t know maples from oaks.” In college he also became interested in other organisms traditionally studied by botanists—like fungi. When he took a class on fungi, he became intrigued by lichens he saw on field trips. His professor was more interested in mushrooms, but LaGreca wanted to learn more, so he specialized in lichens during grad school at Duke, and now lichens are central to his job. He researches them, offers help with identification to other scientists, and is the collections manager for the lichens in the W.L. and C.F. Culberson Lichen Herbarium—all 160,000 of them.
The Duke Herbarium was founded in 1921 by Dr. Hugo Blomquist. It contains more than 825,000 specimens of vascular and nonvascular plants, algae, fungi, and, of course, lichens. Some of those specimens are “type” specimens, meaning they represent species new to science. A type specimen essentially becomes the prototype for its species and “the ultimate arbiter of whether something is species X or not.” But how are lichens identified, anyway?
Lichenologists can consider morphology, habitat, and other traits, but thanks to Dr. Chicita Culberson, who was a chemist and adjunct professor at Duke before her retirement, they have another crucial tool available as well. Culbertson created a game-changing technique to identify lichens using their chemicals, or metabolites, which are often species-specific and thus diagnostic for identification purposes. That technique, still used over fifty years later, is a form of thin-layer chromatography. The process, as LaGreca explains, involves putting extracts from lichen specimens—both the specimens you’re trying to identify and “controls,” or known samples of probable species matches—on silica-backed glass plates. The plates are then immersed in solvents, and the chemicals in the lichens travel up the paper. After the plates have dried, you can look at them under UV light to see if any spots are fluorescing. Then you spray the plates with acid and “bake it for a couple hours.” By the end of the process, the spots of lichen chemicals should be visible even without UV light. If a lichen sample has traveled the same distance up the paper as the control specimen, and if it has a similar color, it’s a match. If not, you can repeat the process with other possible matches until you establish your specimen’s chemistry and, from there, its identity. Culberson’s method helped standardize lichen identification. Her husband also worked with lichens and was a director of the Duke Gardens.
Thin-layer chromatography plates in Dr. LaGreca’s office. The technique, created by Dr. Chicita Culberson, helps scientists identify lichens by comparing their chemical composition to samples of known identity. Each plate was spotted with extracts from different lichen specimens, and then each was immersed in a different solvent, after which the chemicals in the extracts travel up the plate . Each lichen chemical travels a characteristic distance (called the “Rf value”) in each solvent. Here, the sample in column 1 on the rightmost panel matches the control sample in column 2 in terms of distance traveled up the page, indicating that they’re the same species. The sample in column 4, on the other hand, didn’t travel as far as the one in column 5 and has a different color. Therefore, those chemicals (and species) do not match.
LaGreca shows me a workroom devoted to organisms that are cryptogamic, a word meaning “hidden gametes, or hidden sex.” It’s a catch-all term for non-flowering organisms that “zoologists didn’t want to study,” like non-flowering plants, algae, and fungi. It’s here that new lichen samples are processed. The walls of the workroom are adorned with brightly colored lichen posters, plus an ominous sign warning that “Unattended children will be given an espresso and a free puppy.” Tucked away on a shelf, hiding between binders of official-looking documents, is a thin science fiction novel called “Trouble with Lichen” by John Wyndham.
The Culberson Lichen Herbarium itself is a large room lined with rows of cabinets filled with stacks upon stacks of folders and boxes of meticulously organized lichen samples. A few shelves are devoted to lichen-themed books with titles like Lichens De France and Natural History of the Danish Lichens.
Each lichen specimen is stored in an archival (acid-free) paper packet, with a label that says who collected it, where, and on what date. (“They’re very forgiving,” says LaGreca. “You can put them in a paper bag in the field, and then prepare the specimen and its label years later.”) Each voucher is “a record of a particular species growing in a particular place at a particular time.” Information about each specimen is also uploaded to an online database, which makes Duke’s collection widely accessible. Sometimes, scientists from other institutions find themselves in need of physical specimens. They’re in luck, because Duke’s lichen collection is “like a library.” The herbarium fields loan requests and trades samples with herbaria at museums and universities across the globe. (“It’s kind of like exchanging Christmas presents,” says LaGreca. “The herbarium community is a very generous community.”)
Duke’s lichen collection functions like a library in some ways, loaning specimens to other scientists and trading specimens with institutions around the world.
Meticulous records of species, whether in databases of lichens or birds or “pickled fish,” are invaluable. They’re useful for investigating trends over time, like tracking the spread of invasive species or changes in species’ geographic distributions due to climate change. For example, some lichen species that were historically recorded on high peaks in North Carolina and elsewhere are “no longer there” thanks to global warming—mountain summits aren’t as cold as they used to be. Similarly, Henry David Thoreau collected flowering plants at Walden Pond more than 150 years ago, and his samples are still providing valuable information. By comparing them to present-day plants in the same location, scientists can see that flowering times have shifted earlier due to global warming. So why does Duke have tens of thousands of dried lichen samples? “It comes down to the reproducibility of science,” LaGreca says. “A big part of the scientific method is being able to reproduce another researcher’s results by following their methodology. By depositing voucher specimens generated from research projects in herbaria like ours, future workers can verify the results” of such research projects. For example, scientists at other institutions will sometimes borrow Duke’s herbarium specimens to verify that “the species identification is what the label says it is.” Online databases and physical species collections like the herbarium at Duke aren’t just useful for scientists today. They’re preserving data that will still be valuable hundreds of years from now.
Everything in our world is made from materials, meaning life is enabled by material development and efficiency. In today’s society, from constant technological revolution to the global pandemic, life as we know it is always evolving. But as the world around us evolves, the materials around us also need to evolve to keep up with current demands. But how? As a part of Duke University’s annual Research Week on Feb. 3, researchers from a multitude of practices offered their wisdom and research.
Moderated by Dr. Catherine L. Brinson, Ph.D., the panel hosted three Duke Scholars and their research on ‘Materials for a Changing World’. “The development of new materials can really be key in solving some of the more critical challenges of our time,” Brinson maintained.
Dr. David Beratan explaining his research on bio-machines and their material efficiency.
The first scholar to present was R.J Reynolds distinguished professor of chemistry, Dr. David N Beratan, Ph.D. His research concerns the transition from soft, wet, and tiny research machines to more durable, long-term research machines in the science field. “The machines of biology tend to be stochastic and floppy rather than deterministic and hard,” Beratan began. “They’re messy and there are lots of moving parts. They’re intrinsically noisy and error-prone, etc…They’re very different from the kinds of things you see under the hood of your car, and we’d really like to understand how they work and what lessons we might derive from them for our world.” His complex research and research group have aided in bridging the gap in knowledge regarding the transition of biological functional machines to synthetic ones.
Dr.Rubinstein presenting his research on materials at Duke’s Pratt School of Engineering in 2019.
The panel continued with Aleksandar S. Vesic Distinguished Professor in mechanical engineering, Dr. Michael Rubinstein, Ph.D. His research involves the development of self-healing materials across multiple spectrums. “What you want to think about is materials that can heal themselves,” he stated. “If there’s a crack or a failure in a material, we would like the material to heal itself without external perturbation involvement. So it could be done by the other diffusion of molecules across some physical approaches, or by a chemical approach where you have bonds that were broken to the form.” His research on this possibility has made strides in the scientific field, especially in a time of such ecological stress and demand for materials.
Dr. Segura talking with Dr. Brinson on her research involving self-healing materials.
The panel concluded with biomedical engineering professor Dr. Tatiana Segura, Ph.D. Segura talked about work they are doing at their lab regarding materials that can be used to heal the human body after damage or injury. She began by mentioning that “we are a materials lab and that’s what we’re interested in designing. So what are we inspired by? Well, we are really inspired by the ability of our body to heal.” At her lab, a primary motivation is healing disabilities after a stroke. “Sometimes you have something that you deal with for a long time no matter how your body healed. And that inspires us to consider how do we actually engage this process with materials to make it go better and actually make our body heal in a way that we can promote repair and regeneration.” Understanding this process is a complex one, she explained, but one that she believes is crucial in understanding the design of the material.
‘Materials for a Changing World’ was yet another extremely powerful speaker series offered this year during Duke Research Week. Our world is changing, and our materials need to keep up. With the help of these experts, material innovation has a bright future.
Cypress swamp, eastern North Carolina. Photo by Steve Anderson, Duke
DURHAM, N.C. — The Albemarle-Pamlico Peninsula covers more than 2,000 square miles on the North Carolina coastal plain, a vast expanse of forested swamps and tea-colored creeks. Many people would probably avoid this place, whose dense thickets of cane and shrubs and waterlogged soils can slow a hike to a crawl.
“It’s hard fieldwork,” says Duke researcher Steve Anderson. “It gets really dense and scratchy. That, plus the heat and humidity mixed with the smell of sulfur and the ticks and the poison ivy; it just kind of adds up.”
But to Anderson and colleagues from Duke and North Carolina State University, these bottomlands are more than impenetrable marsh and muck and mosquitoes. They’re also a barometer of change.
Researchers surveying plants in Alligator River National Wildlife Refuge in 2016. Photo by Mathew Stillwagon, North Carolina State University
Most of the area they study lies a mere two to three feet above sea level, which exposes it to surges of ocean water — 400 times saltier than freshwater — driven inland by storms and rising seas. The salt deposits left behind when these waters recede build up year after year, until eventually they become too much for some plants to cope with.
Trudging in hip waders through stunted shrubs and rotting tree stumps, Anderson snaps a picture with his phone of a carpet of partridge berry trailing along the forest floor. In some parts of the peninsula, he says, the soils are becoming so salty that plants like these can no longer reproduce or are dying off entirely.
Along the North Carolina coast, understory plants such as this partridge berry (left) are quickly ceding ground to species such as this bigleaf marsh-elder (right) as the soils become too salty for them to thrive. Credit: Steve Anderson
In a recent study the team, led by professors Justin Wright and Emily Bernhardt of Duke, and Marcelo Ardón of NC State, surveyed some 112 understory plants in the region, making note of where they were found and how abundant they were in relation to salt levels in the soil.
The researchers identified a ‘tipping point,’ around 265 parts per million sodium, where even tiny changes in salinity can set off disproportionately large changes in the plants that live there.
Above this critical threshold, the makeup of the marsh floor suddenly shifts, as plants such as wax myrtle, swamp bay and pennywort are taken over by rushes, reeds and other plants that can better tolerate salty soils.
Certain dwindling plants could be an early warning sign that salt is poisoning inland waters, researchers say. Credit: Steve Anderson
The hope is that monitoring indicator species like these could help researchers spot the early warning signs of salt stress, Anderson says.
This research was supported by grants from the National Science Foundation (DEB1713435, DEB 1713502, and Coastal SEES Collaborative Research Award Grant No. 1426802).
CITATION: “Salinity Thresholds for Understory Plants in Coastal Wetlands,” Anderson, S. M., E. A. Ury, P. J. Taillie, E. A. Ungberg, C. E. Moorman, B. Poulter, M. Ardón, E. S. Bernhardt, and J. P. Wright. Plant Ecology, Nov. 24, 2021. DOI: 10.1007/s11258-021-01209-2.
Salt is poisoning the soils past a point of no return for some marsh plants; one team is trying to pinpoint the early warning signs. By Steve Anderson.
In 2011, Dr. Jennifer Doudna began studying an enzyme called Cas9. Little did she know, in 2020 she would go on to win the Nobel Prize in Chemistry along with Emmanuelle Charpentier for discovering the powerful gene-editing tool, CRISPR-Cas9. Today, Doudna is a decorated researcher, the Li Ka Shing Chancellors Chair, a Professor in the Department of Chemistry and Molecular as well as Cell Biology at the University of California Berkeley, and the founder of the Innovative Genomics Institute.
Doudna was also this year’s speaker for the MEDx Distinguished Lecture in October where she delivered presented on “CRISPR: Rewriting DNA and the Future of Humanity.”
“CRISPR is a system that originated in bacteria as an adaptive immune system” Doudna explained.
Dr. Jennifer Doudna holding the Nobel Prize in Chemistry
When bacterial cells are infected by viruses those viruses inject their genetic material into the cell. This discovery, a couple decades ago, was the first indication that there may be ways to apply bacteria’s ability to acquire genetic information from viruses.
CRISPR itself was discovered in 1987 and stands for “Clustered Regularly Interspaced Short Palindromic Repeats.” Doudna was initially studying RNA when she discovered Cas-9, a bacterial RNA-guided endonuclease and one of the enzymes produced by the CRISPR system. In 2012, Doudna and her colleagues found that Cas9 used base pairing to locate and splice target DNAs when combined with a guide RNA.
Essentially, they designed guide RNA to target specific cells. If those cells had a CRISPR system encoded in their genome, the cell is able to make an RNA copy of the CRISPR locus. Those RNA molecules are then processed into units that each include a sequence derived from a virus and then assemble with proteins. This RNA protein then looks for DNA sequences that match the sequence in the RNA guide. Once a match occurs, Cas9 is able to bind to and cut the DNA, leading to the destruction of the viral genome. The cutting of DNA then triggers DNA repair allowing gene editing to occur.
“This system has been harnessed as a technology for genome editing because of the ability of these proteins, these CRISPR Cas-p proteins, to be programmed by RNA molecules to cut any desired DNA sequence,” Doudna said.
CRISPR-cas9 is also being applied in many clinical settings. In fact, when the COVID-19 pandemic hit, Doudna along with several colleagues organized a five-lab consortium including the labs of Dan Fletcher, Patrick Hsu, Melanie Ott, and David Savage. The focus was on developing the Cas13 system to detect COVID-19. Cas13 is a class of proteins, that are RNA guided, RNA targeting, CRISPR enzymes. This research was initially done by one of Doudna’s former graduate students, Alexandra East-Seletsky. They discovered that if the reporter RNA is is paired with enzymes that have a quenched fluorophore pair on the ends, when the target is activated, the reporter is cleaved and a fluorescent signal is released.
One study out of the Melanie Ott group demonstrated that Cas13 can be used to detect viral RNA. They are hoping to apply this as a point-of-care diagnostic by using a detector as well as a microfluidic chip which would allow for the conduction of these chemical reactions in much smaller volumes that can then be read out by a laser. Currently, the detection limit is similar to what one can get with a PCR reaction however it is significantly easier to run.
Graphical Abstract of Cas13 Research by the Melanie Ott lab
“And this is again, not fantasy, we’ve actually had just fabricated devices that will be sitting on a benchtop, and are able to use fabricated chips that will allow us to run the Cas13 chemistry with either nasal swab samples or saliva samples for detection of the virus,” Doudna added.
Another exciting development is the use of genome editing in somatic cells. This involves making changes in the cells of an individual as opposed to the germline. One example is sickle cell disease which is caused by a single base pair defect in a gene. Soon, clinicians will be able to target and correct this defect at the source of the mutation alleviating people from this devastating illness. Currently, there are multiple ongoing clinical trials including one at the Innovative Genomics Institute run by Doudna. In fact, one patient, Victoria Gray, has already been treated for her sickle cell disease using CRISPR.
Victoria Gray being treated for Sickle Cell Anemia Meredith Rizzo/NPR
“The results of these trials are incredibly exciting and encouraging to all of us in the field, with the knowledge that this technology is being deployed to have a positive impact on patient’s lives,” Doudna said.
Another important advancement was made last summer involving the use of CRISPR-based therapy to treat ATR, a rare genetic disease that primarily affects the liver. This is also the first time CRISPR molecules will be delivered in vivo.
In just 10 years CRISPR-cas9 has gone from an exciting discovery to being applied in several medical and agricultural settings.
“This powerful technology enables scientists to change DNA with precision only dreamed of a few years ago,” said MEDx director Geoffrey Ginsburg, a Professor of Medicine at Duke. “Labs worldwide have redirected the course of research programs to incorporate this new tool, creating a CRISPR revolution with huge implications across biology and medicine.”
Examples of further CRISPR-Cas9 research can also be found in the Charles Gersbach lab here at Duke.
Tiffany Yen, a Duke junior majoring in chemistry, grew up in the sunny suburbs of Los Angeles, never too far from the coastline. She’s always loved being outside, especially in California where there is no shortage of trails to hike and beaches to go to. Friends know her as a Patagonia aficionado, going so far as to buy her a book profiling the company’s business model for her birthday. In fact, from Yen, I learned that every Patagonia store gives out city-specific stickers, so if you feel so inclined, you can collect them (as Yen obviously does). All this is to say: Tiffany Yen has always been interested in sustainability.
“I never understood why what we do has to come at the cost of the planet,” Yen said, in discussing how her years in school learning about climate change fueled her passion for sustainable science. “The environment is so important. Without it, we wouldn’t be here.”
Tiffany Yen
Unsure of what she wanted to study at Duke and where she wanted to go post-graduation, she decided to take her two interests – sustainability and chemistry, particularly polymer chemistry – and see what she could do to combine them. She knew coming into college that she wanted to do research, so that landed her at the Becker Lab for Functional Materials.
The Becker Lab is a multidisciplinary organic materials lab focused on biomedical applications – specifically, things like adhesives and drug delivery. Yen works on improvements to intercranial pressure sensors. Traditionally, after head trauma, doctors need to measure the intercranial space to see if the brain is damaged. The sensor that is used is wired and tends to be a very invasive procedure – the probe is connected to a machine outside, and there’s a high risk of infection.
Collaborators at Northwestern developed a biodegradable wireless device that, after implantation, doesn’t require a secondary procedure to take out. The problem is that it degrades a little too fast – and so measurements can’t be taken. Yen, with her mentor, is working on building a film encapsulation to make it possible for the device to take good measurements.
Right now, they’re trying out azelaic acid instead of succinic acid. Azelaic acid has favorable anti-inflammatory properties and is commonly used in acne medications. It could also potentially increase the bioresorbability of the polymer. Their hope is that the film not only helps the body metabolize more of the polymer, but actually helps in healing.
Snapshots from Yen’s life at the lab
So why medical research? Yen explains that while her work may not seem obviously linked to sustainability, the push for finding materials that can degrade is extremely relevant. And while she’s not all that interested in medicine specifically, she likes things that are practical and applicable.
“When I did research in the past,” Yen said, “there wasn’t always an application. It sometimes was about synthesizing something, just for the sake of science.” And while there’s certainly value in strengthening science fundamentals, she admits that research in that vein doesn’t really appeal to her. “I want to work on things that I directly see adding value to society.”
After college, Yen sees herself going to graduate school and working towards a PhD in “some physical science related to chemistry.” Ultimately, her goal is to work at the interface of venture capital and scientific research, using her science background to find and fund promising innovations in sustainability. “There are so many incredible things being researched out there,” Yen says, “but the biggest problem in research is funding and commercializing.” She continues, “I think there are other people out there who can do better research than I can, so I want to go out there, find the stuff, and fund it.”
Yen has come to believe that just because she dedicated her time at Duke to science, it doesn’t mean she needs to stay in science forever. There’s value in scientific knowledge no matter where you go. And as businesses realize that public interest in sustainability is growing, she’s crossing her fingers that her skillset will poise her to be a valuable asset in seeking out new innovations.
Snapshots from Yen’s life at the lab
She said that when she came into college, she felt a pressure to pursue a more traditional path, like being pre-med. “I value stability, and I’m very risk-averse,” she laughs.
But when she asked herself what she’d be happiest doing, she knew it would be trying to save the planet in some way. But she clarifies: “At this point, I can’t save the planet. I think that’s a very far-fetched thing for one person to do.” Instead, “I’d rather try and maybe fail than not try at all.”
My name is Olivia Ares (she/her), and I’d like to provide the opportunity for you to get to know me better. In true blog post fashion, here are some quick facts at the outset:
Those close to me claim I have a “cardigan problem.” (By that, they mean that I own an obscene amount of cardigans. If you ask me, that sounds like the exact opposite of a problem.)
Pictured here is my green three-quarter sleeve cardigan with flower-shaped buttons, which provides a colorful accent.
You may be asking yourself what interest I could possibly have in being a research blogger, since I’m clearly destined for a future in comedy (or cardigan connoisseurship). And especially since, as you’ll soon learn, I’m not a science person.
Like a lot of people during our year of virtual school, I went through a lifetime of hobby phases in a matter of months. I started with baking, which only lasted until the bread flour ran out. I watched a lot of movies that I had always wanted to see (which often disappointed), and I rewatched a lot of movies I loved (which never disappointed). I tried learning the guitar, but I never practiced enough to build up the right callouses, so I never practiced at all. I discovered a love for puzzles and an utter lack of skill for them. I downloaded The Sims 4 on a free trial, spent months building a super cool house, then deleted the whole game.
My three favorite things in one picture: lavender cold brew, Taylor Swift, and my blue wool cardigan.
The only thing that’s stuck so far has been reading. In middle school, we used to stay up late with a flashlight under our covers to finish books, then abruptly lost all motivation somewhere between The Giver and The Scarlet Letter. I think we forgot along the way that there are no rules to reading; there’s no one to impress. There’s no one to sample your sourdough or judge your twangy, painful acoustic cover of “Three Blind Mice.” Reading is something you do purely for yourself.
Reading makes information and ideas universally accessible; it connects worlds using only ink on a page. There’s this myth that analytical minds are not creative minds and vice versa, and it alienates people: people who would bring such great perspectives to the table if they hadn’t been defined by a checklist of abilities. Reading is for everyone to find what they love and to love what they find (or hate it; one of the great things about doing things for yourself is that you can just quit whenever you want to).
Scientific research, on the other hand, is something produced for everyone. Humans exploring more and more about the world is something that affects all of us, despite the research being conducted only by a select few of us.
My black long-sleeve cardigan is a personal favorite, as it goes with pretty much everything.
Freshman year of high school, I finished chemistry with a B, which was a miracle considering I was rocking a D around November. I had to change my way of looking at the material; I couldn’t remember the makeup of an atom, but I could remember it if I thought about the stories of individuals who built off of each model in succession. I didn’t understand stoichiometry, but I did understand you have to balance equations just like weights on a scale or kids on a see-saw.
My point is: everyone sees things differently. Exclusivity in different fields is fabricated to make information and education elitist, and it is not reflective of individuals’ ability to understand the world. If you want to read about cool science stuff, you shouldn’t feel left out because you’re more of an art history person. If you want to read about cool art history stuff, you shouldn’t feel left out because you’re an aerospace engineer.
So I like to think that I can be that bridge for some people; at the very least, I can do it for myself.
Engineers, medical students, ecologists, political scientists, ethicists, policymakers — come one, come all to the Duke Space Initiative (DSI), “the interdisciplinary home for all things space at Duke.”
At Duke Polis’ “Perspectives on Space: Introducing the Duke Space Initiative” on Sept. 9, DSI co-founder and undergraduate student Ritika Saligram introduced the initiative and moderated a discussion on the current landscape of space studies both at Duke and beyond.
William R. & Thomas L. Perkins Professor of Law Jonathan Wiener began by expressing his excitement in the amount of interest he’s observed in space at Duke.
One of these interested students was Spencer Kaplan. Kaplan, an undergraduate student studying public policy, couldn’t attend Wiener’s Science & Society Dinner Dialogue about policy and risk in the settlement of Mars. Unwilling to miss the learning opportunity, Kaplan set up a one-on-one conversation with Wiener. One thing led to another: the two created a readings course on space law — Wiener hired Kaplan as a research assistant and they worked together to compile materials for the syllabus — then thought, “Why stop there?”
Wiener and Kaplan, together with Chase Hamilton, Jory Weintraub, Tyler Felgenhauer, Dan Buckland, and Somia Youssef, created the Bass Connections project “Going to Mars: Science, Society, and Sustainability,” through which a highly interdisciplinary team of faculty and students discussed problems ranging from the science and technology of getting to Mars, to the social and political reality of living on another planet.
The team produced a website, research papers, policy memos and recommendations, and a policy report for stakeholders including NASA and some prestigious actors in the private sector. According to Saligram, through their work, the team realized the need for a concerted “space for space” at Duke, and the DSI was born. The Initiative seeks to serve more immediately as a resource center for higher education on space, and eventually as the home of a space studies certificate program for undergraduates at Duke.
Wiener sees space as an “opportunity to reflect on what we’ve learned from being on Earth” — to consider how we could avoid mistakes made here and “try to do better if we settle another planet.” He listed a few of the many problems that the Bass Connections examined.
The economics of space exploration have changed: once, national governments funded space exploration; now, private companies like SpaceX, Blue Origin, and Virgin Galactic seek to run the show. Space debris, satellite and launch junk that could impair future launches, is the tragedy of the commons at work — in space. How would we resolve international disputes on other planets and avoid conflict, especially when settlements have different missions? Can we develop technology to ward off asteroids? What if we unintentionally brought microorganisms from one planet to another? How will we make the rules for the settlement of other planets?
These questions are vast — thereby reflecting the vastness of space, commented Saligram — and weren’t answerable within the hour. However, cutting edge research and thinking around them can be found on the Bass Connections’ website.
Earth and Climate Sciences Senior Lecturer Alexander Glass added to Wiener’s list of problems: “terraforming” — or creating a human habitat — on Mars. According to Glass, oxygen “isn’t a huge issue”: MOXIE can buzz Co2 with electricity to produce it. A greater concern is radiation. Without Earth’s magnetosphere, shielding of some sort will be necessary; it takes sixteen feet of rock to produce the same protection. Humans on Mars might have to live underground.
Glass noted that although “we have the science to solve a lot of these problems, the science we’re lagging in is the human aspects of it: the psychological, of humanity living in conditions like isolation.” The engineering could be rock solid. But the mission “will fail because there will be a sociopath we couldn’t predict beforehand.”
Bass Connections project leader and PhD candidate in political science Somia Youssef discussed the need to examine deeply our laws, systems, and culture. Youssef emphasized that we humans have been on Earth for six million years. Like Wiener, she asked how we will “apply what we’ve learned to space” and what changes we should make. How, she mused, do prevailing ideas about humanity “transform in the confines, the harsh environment of space?” Youssef urged the balancing of unity with protection of the things that make us different, as well as consideration for voices that aren’t being represented.
Material Science Professor, Assistant Professor of Surgery, and NASA Human System Risk Manager Dr. Dan Buckland explained that automation has exciting potential in improving medical care in space. If robots can do the “most dangerous aspects” of mission medical care, humans won’t have to. Offloading onto “repeatable devices” will reduce the amount of accidents and medical capabilities needed in space.
Multiple panelists also discussed the “false dichotomy” between spending resources on space and back home on Earth. Youssef pointed out that many innovations which have benefited (or will benefit) earthly humanity have come from the excitement and passion that comes from investing in space. Saligram stated that space is an “extension of the same social and policy issues as the ones we face on Earth, just in a different context.” This means that solutions we find in our attempt to settle Mars and explore the universe can be “reverse engineered” to help Earth-dwelling humans everywhere.
Saligram opened up the panel for discussion, and one guest asked Buckland how he ended up working for NASA. Buckland said his advice was to “be in rooms you’re not really supposed to be in, and eventually people will start thinking you’re supposed to be there.”
Youssef echoed this view, expressing the need for diverse perspectives in space exploration. She’s most excited by all the people “who are interested in space, but don’t know if there’s enough space for them.”
If this sounds like you, check out the Duke Space Initiative. They’ve got space.
Imagine: you wake on a chilly November morning, alarm blaring, for your 8:30 am class. You toss aside the blankets and grab your phone. Shutting the alarm off reveals a Washington Post notification. But this isn’t your standard election headline. You almost drop your phone in shock. It can’t be, you think. This is too good to be true. It’s not — a second later, you get a text from the SymMon app, notifying you of your upcoming appointment in the Bryan Center.
A vaccine for COVID-19 is finally available, and you’re getting one.
This scenario could be less far-fetched than one might think: the Centers for Disease Control and Prevention has told officials to prepare for a vaccine as soon as November 1st. To a country foundering due to the economic and social effects of COVID-19, this comes as incredible news — a bright spot on a bleak horizon. But to make a vaccine a reality, traditional phase 3 clinical trials may not be enough. What are challenge trials? Should they be used? What’s at stake, and what are the ethical implications of the path we choose?
Dr. Marc Lipsitch, Director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health, began by comparing traditional phase 3 trials and challenge trials.
In both kinds of trials, vaccines are tested for their “safety and ability to provoke an immune response” in phases 1 and 2. In phase 3 trials, large numbers (typically thousands or tens of thousands) of individuals are randomly assigned either the vaccine being tested or a placebo. Scientists observe how many vaccinated individuals become infected compared to participants who received a placebo. This information enables scientists to assess the efficacy — as well as rarer side effects — of the vaccine.
Marc Lipsitch
In challenge trials, instead of random assignment, small numbers of low-risk individuals are deliberately infected in order to more directly study the efficacy of vaccine and treatment candidates. Though none are underway yet, the advocacy group 1Day Sooner has built a list of more than 35,000 volunteers willing to participate.
Dr. Cameron Wolfe, an Infectious Disease Specialist, Associate Professor of Medicine, and Clinical Expert In Respiratory and Infectious Disease at the Duke Medical School, provided an overview of the current vaccine landscape.
Cameron Wolfe
There are currently at least 150 potential vaccine candidates, from preclinical to approved stages of development. Two vaccines, developed by Russia’s Gamelaya Research Institute and China’s CanSinoBIO, have skipped phase 3, but are little more than an idiosyncrasy to Dr. Wolfe, as there is “minimal clarity about their safety and efficacy.” Three more vaccines of interest — Moderna’s mRNA vaccine, Pfizer’s mRNA vaccine, and Oxford and AstraZeneca’s adenovirus vaccine — are all in phase 3 trials with around 30,000 enrollees. Scientists will be watching for a “meaningful infection and a durable immune response.”
Dr. Nir Eyal, the Henry Rutgers Professor of Bioethics and Director of The Center for Population-Level Bioethics at Rutgers University, explained how challenge trials could fit into the vaccine roadmap.
According to Dr. Eyal, challenge trials would most likely be combined with phase 3 trials. One way this could look is the use of challenge trials to weed out vaccine candidates before undergoing more expensive phase 3 trials. Additionally, if phase 3 trials fail to produce meaningful results about efficacy, a challenge trial could be used to obtain information while still collecting safety data from the more comprehensive phase 3 trial.
Nir Eyal
Dr. Eyal emphasized the importance of challenge trials for expediting the arrival of the vaccine. According to his own calculations, getting a vaccine — and making it widely available — just one month sooner would avert the loss of 720,000 years of life and 40 million years of poverty, mostly concentrated in the developing world. (Dr. Eyal stressed that his estimate is extremely conservative as it neglects many factors, including loss of life from avoidance of child vaccines, cancer care, malaria treatment, etc.) Therefore, speed is of “great humanitarian value.”
Dr. Wolfe added that because phase 3 trials rely on a lot of transmission, if the US gets better at mitigating the virus, “the distinction between protective efficacy and simple placebo will take longer to see.” A challenge study, however, is “always a well defined time period… you can anticipate when you’ll get results.”
The panelists then discussed the ethics of challenge trials in the absence of effective treatment — as Krawiec put it, “making people sick without knowing if we can make them better.”
Dr. Wolfe pointed to the flu, citing challenge trialsthat havebeen conducted even though current treatments are not uniformly effective (“tamiflu is no panacea”). He then conceded that the biggest challenge is not a lack of effective therapies, but the current inability to “say to a patient, ‘you will not have a severe outcome.’ It varies so much from person to person, I guess.” (See one troubling example of that variance.)
Dr. Eyal acknowledged the trouble of informed consent when the implications are scarcely known, but argued that “in extraordinary times, business as usual is no longer the standard.” He asserted that if people volunteer with full understanding of what they are committing to, there is no reason to assume they are less informed than when making other decisions where the outcome is as yet unknown.
Dr. Lipsitch compared this to the military: “we are not cheating if we cannot provide a roadmap of future wars because they are not yet known to us.” Rather, we commend brave soldiers (and hope they come home safe).
Furthermore, Dr. Eyal asserted that “informed consent is not a comprehensive understanding of the disease,” lest much of the epidemiological research from the 1970s be called into question too. Instead, volunteers should be considered informed as long as they comprehend questions like, “‘we can’t give you an exact figure yet; do you understand?’”
Agreeing, Dr. Wolfe stated that when critics of challenge trials ask, isn’t your mission to do no harm?, he asks, “Do no harm in regards to whom?” “Who is in front of you matters,” Dr. Wolfe confirmed, “that’s why we put up safeguards. But as clinicians it can be problematic [to stop there]. It’s not just about the patient, but to do no harm in regards to the broader community.”
The experts then discussed what they’d like to see in challenge trials.
Dr. Wolfe said he’d like to see challenge trials carried out with a focus on immunology components, side effect profiles, and a “barrage” of biological safety and health standards for hospitals and facilities.
Dr. Eyal stated the need for exclusion criteria (young adults, perhaps age 20-25, with no risk factors), a “high high high” quality of informed consent ideally involving a third party, and access to therapies and critical care for all volunteers, even those without insurance.
Dr. Lipsitch stressed the scientific importance of assessing participants from a “virological, not symptom bent.” He mused that the issue of viral inoculum was a thorny one — should scientists “titrate down” to where many participants won’t get infected and more volunteers will be needed overall? Or should scientists keep it concentrated, and contend with the increased risk?
Like many questions pondered during the hour — from the ideal viral strain to use to the safest way to collect information about high risk patients — this one remained unanswered.
So don’t mark November 1st on your calendar just yet. But if you do get that life-changing notification, there’s a chance you’ll have human challenge trials to thank.
