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Nobel Laureate Dr. Jennifer Doudna and Groundbreaking Applications of CRISPR

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.

Jennifer Doudna holding a Model of CRISPR-cas9

While continuing to conduct research, Doudna has also been focused on applying CRISPR in agriculture and medicine. For agriculture, researchers are looking to make changes to the genomes of plants in order to improve drought resistance and crop protection. 

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. 

By Anna Gotskind, Class of 2022

Duke has 38 of the World’s Most Highly-Cited Scientists

Peak achievement in the sciences isn’t measured by stopwatches or goals scored, it goes by citations – the number of times other scientists have referenced your findings in their own academic papers. A high number of citations is an indication that a particular work was influential in moving the field forward.

Nobel laureate Bob Lefkowitz made the list in two categories this year.

And the peak of this peak is the annual “Highly Cited Researchers” list produced each year by the folks at Clarivate, who run the Institute for Scientific Information. The names on this list are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index – the most-cited of the cited.

Duke has 38 names on the highly cited list this year — including Bob Lefkowitz twice because he’s just that good — and two colleagues at the Duke NUS Medical School in Singapore. In all, the 2021 list includes 6,602 researchers from more than 70 countries.

The ISI says that US scientists are a little less than 40 percent of the highly cited list this year – and dropping. Chinese researchers are gaining, having nearly doubled their presence on the roster in the last four years.

“The headline story is one of sizeable gains for Mainland China and a decline for the United States, particularly when you look at the trends over the last four years,” said a statement from David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information. “(This reflects) a transformational rebalancing of scientific and scholarly contributions at the top level through the globalization of the research enterprise.”

Without further ado, let’s see who our champions are!

Biology and Biochemistry

Charles A. Gersbach

Robert J. Lefkowitz

Clinical Medicine

Pamela S. Douglas

Christopher Bull Granger

Adrian F. Hernandez

Manesh R.Patel

Eric D. Peterson

Cross-Field

Richard Becker

Antonio Bertoletti (NUS)

Yiran Chen

Stefano Curtarolo

Derek J. Hausenloy (NUS)

Ru-Rong Ji

Jie Liu

Jason W. Locasale

David B. Mitzi

Christopher B. Newgard

Ram Oren

David R. Smith

Heather M. Stapleton

Avner Vengosh

Mark R. Wiesner

Environment and Ecology

Emily S. Bernhardt

Geosciences

Drew T. Shindell

Immunology

Edward A. Miao

Microbiology

Barton F. Haynes

Neuroscience and Behavior

Quinn T. Ostrom

Pharmacology and Toxicology

Robert J. Lefkowitz

Plant and Animal Science

Xinnian Dong

Sheng Yang He

Philip N. Benfey

Psychiatry and Psychology

Avshalom Caspi

E. Jane Costello

Honalee Harrington

Renate M. Houts

Terrie E. Moffitt

Social Sciences

Michael J. Pencina

Bryce B. Reeve

John W. Williams

Post by Karl Bates

How Freshman Engineers Solve Real-World Problems in EGR 101

The sound of drills whirring, the smell of heated plastic from the 3D printers, and trying to see through foggy goggles. As distracting as it may sound, this is a normal day for a first-year engineering student (including myself) in class. 

During these past few weeks, freshmen engineers have been brainstorming and building projects that have piqued their interest in their EGR101 class. Wanting to know more, I couldn’t help but approach Amanda Smith, Jaden Fisher, Myers Murphy, and Christopher Cosby, and ask about their goal to make an assistive device to help people with limited mobility take trash cans up an inclined driveway that is slippery and wet.

“Our client noticed the problem in his neighborhood in Chapel Hill with its mainly-elderly population, and asked for a solution to help them,” Fisher says. “We thought it would be cool to give back to the community.” Their solution: a spool with a motor. 

Coming from a mechanical engineering mindset, the team came up with the idea to create a spool-like object that has ropes that connect to the trash can, and with a motor, it would twist, pull up the trash can, and then slowly unroll it back down the driveway. As of now, they are currently in the prototyping phase, but they are continuing to work hard nonetheless. 

“For now, our goal is to slowly begin to scale up and hopefully be able to make it carry a full trash can. Maybe one day, our clients can implement it in real life and help the people that need it,” says Smith.

Low-fidelity prototype of the spool

All of this planning and building is part of the Engineering Design & Communication class, also known as EGR 101, which all Pratt students have to take in their first year. Students are taught about the engineering design process, and then assigned a project to implement what they learned in a real life situation by the end of the semester.

“This is a very active learning type of class, with an emphasis on the design process,” says Chip Bobbert, one of the EGR 101 professors. “We think early exposure will be something that will carry forward with student’s careers.”

Not only do the students deal with local clients, but some take on problems from  nationwide companies, like Vivek Tarapara, Will Denton, Del Cudjoe, Ken Kalin, Desmond Decker, and their client, SKANSKA, a global construction company.

“They have an issue scheduling deliveries of materials to their subcontractors, which causes many issues like getting things late, dropped in the wrong areas, etc.,” Tarapara explains. “There is a white board in these construction sites, but with people erasing things and illegible handwriting, we want to make a software-based organizational tool so that everyone involved in the construction is on the same page.”

Watching the team test their code and explain to me each part of their software, I see they have successfully developed an online form that can be accessed with a QR code at the construction site or through a website. It would input the information on a calendar so that users can see everything at any time, where anyone can access it, and a text bot to help facilitate the details.

“We are currently still working on making it look better and more fluid, and make a final solution that SKANSKA will be satisfied with,” Denton says, as he continues to type away at his code.

Vivek Tarapara (left) and Will Denton (right) working on their code and text bot

One final project, brought up by Duke oral surgeon Katharine Ciarrocca, consists of students Abigail Paris, Fernando Rodriguez, Konur Nordberg, and Camila Cordero (hey, that’s me!), and their mouth prop design project. 

After many trials and errors, my team has created a solution that we are currently in the works of printing with liquid silicone rubber. “We have made a bite block pair, connected by a horizontal prism with a gap to clip on, as well as elevated it to give space for the tongue to rest naturally,” Paris elaborates.

The motivation behind this project comes from COVID-19. With the increase of ICU patients, many receiving endotracheal intubations, doctors have come to realize that these intubations are causing other health issues such as pressure necrosis, biting on the tongue, and bruising from the lip. Dr. Ciarrocca decided to ask the EGR 101 class to come up with a device to help reduce such injuries.

Medium-fidelity prototype of mouth prop inside of mouth model with an endotracheal intubation tube

Being part of this class and having first-hand look at all the upcoming projects, it’s surprising to see freshman students already working on such real-world problems.

“One of the things I love about engineering and this course is that we’re governed by physics and power, and it all comes to bear,” says Steven McClelland, another EGR 101 professor. “So this reckoning of using the real world and beginning to take theory and take everything into consideration, it’s fascinating to see the students finally step into reality.”

Not only does it push freshmen to test their creativity, but it also creates a sense of teamwork and bonding between classmates, even in the most unordinary class setting.

“I look around the room and there’s someone wearing a pool noodle, another boiling alcohol, and another trying to measure the inside of their mouth,” says Bobberts as he scans the area quickly. “I’m excited to see people going and doing stuff together.”

Post by Camila Codero, Class of 2025

New Blogger Nidhi Srivaths: Attracted by Words

Before I moved to the U.S, the concept of a “Starbucks name” was foreign to me, but after six cups of coffee that read everything from “Nemo” to just an unintelligible scrawl, I understood the need for it. Back home in India, my name was quite common, but having to repeat myself multiple times only to still be misheard made suddenly made feel unusually unique.

Speech can often be tricky, and growing up in a family that speaks four languages interchangeably, I’ve always been acutely aware of that. Missing a tongue roll on the word for “tell” in Kannada makes it dinner-table inappropriate, and a small vowel slip in Telugu can completely alter conversational context. I lived in India’s objectively best city, Hyderabad, that has its special version of Hindi, which was unacceptable in conversation with my mother’s own dialect. Language was thus the most unique part of my upbringing, and the unconventionally twisted sentences that combined the vocabulary of two languages and the grammar of another are characteristic of my childhood.

Raised amidst the chaotic storm of my family’s polyglotism, I found my shelter under the pages of books. Writing soon became a beautiful structure of stability for me, and the decisiveness of ink on paper drew me to it. At first, I began to read simply because I loved dragging my finger across the smooth finish of my brother’s gigantic encyclopedia but soon my childish captivation with the book turned to fascination with its contents. I loved hunting for and sounding out difficult words, and my favorite ones would always be the scientific terms.

So, the world of science was the logical next destination.

My strange love for the word “bioluminescence” led me to the ocean, and for months, I dreamed of glowing plankton and starfish. When “constellation” caught my fancy, I spent years imagining myself flying through the vast expanse of outer space, journeying to the very ends of the universe as an astronaut. From the cozy confines of my bedroom, I traversed through Egyptian ruins with “pharaoh”, Norse myths with “valkyrie” and dinosaur dig sites with “paleontology.” Finally, it was an anatomy book that bound me to the world of healthcare and the human body, and my brother’s weekly technology magazine that pulled me towards automation, before I settled on the middle ground I now love – biomedical engineering. Now a sophomore majoring in BME and ECE, I learn new words every day!

Scientific innovations and advancements are often looked at as difficult to understand, discouraging many from learning more about them. But science is embedded in every facet of our daily lives, and I believe it is essential (now, more than ever!) that its literature and progress become more accessible and understandable. As a child, it was the simple, clear and concise language of informal blogs and books that convinced me that I belonged in the fields I read about, and as a blogger, I want to convince many more that the world of science is well within their reach! Fancy terms like glycolysis may seem daunting, but everything can be broken down and made simpler (in this case, quite literally!). Blogging for Duke Research, I hope to meet trailblazers, learn and write about research that fascinates me, and make it accessible to more people. Along the way, I want to introduce the next inquisitive little girl to the exotic word that feeds her imagination, propelling her into the world of science!

However, beyond my selfless mission of spreading the good word of science and technology far and wide, I recently found a new, far more relatable reason to love writing – I don’t need a Starbucks name! It’s a lot easier to just tell you my name is Nidhi.

Post by Nidhi Srivaths, Class of 2024

New Blogger Camila Cordero: Renaissance First-Year

My name is Camila Cordero, and for those who know Spanish: yes, my last name does mean lamb. I’m a Hispanic female, born and raised in Miami, Florida. Living in Miami, one can think of many stereotypes (don’t pretend). You have the terrible traffic, the apocalyptic heat, and the international sensation, “Despacito” played everywhere.

Having a civil engineer as a father and an agriculture specialist as a mother, I became the best of both worlds as someone who now seeks to pursue a degree in Biomedical Engineering, interested in following pre-health as well.

To say I have a ‘passion’ in the sciences would be an understatement. Ever since I was a young person, I have always been curious about the world around me; questioning why things happen, how things occur, and what composes of things. It came to no surprise that in elementary school, I was already competing in multiple science competitions, broadening my range of knowledge. At first, I was drawn into the world of cartography and mechanical engineering– drawing profiles and building Rube Goldberg machines at the young age of 11. Yet, in just a span of a few years, I continued my journey into the unknowns of science, later figuring out that my true calling falls in the world of biology.

But don’t think I cut myself short there! Having such an excitement to be taught and taking every opportunity to acquire a new skill, I can see myself in the future as a Renaissance woman. Just as easy as it is for me to sketch you a beautiful drawing, I can also figure skate on ice, talk to you in Spanish or Greek, and change a NASCAR stock car tire. From here, who knows what else I will do in these next four years at Duke!

Writing for the Duke Research Blog, I seek to learn yet another ability: to write. Having written short stories for writing competitions and speeches in school, I seek to perfect this skill through the blog. Not only will I practice my writing, but I will continue to explore the world of science that I love so deeply with the help of others. I hope that with my writing, I will be able to reach out to the public and teach them about the scientific research that can impact the world for the better.

Post by Camila Cordero, Class of 2025

New Blogger Vibhav Nandagiri: The Curious Student Blogger

Hey everyone! My name is Vibhav Nandagiri, I use he/him/his pronouns, and I’m currently a first-year student at Duke. Amidst the sea of continuous transition brought upon by college, one area of my identity that has stayed fairly constant is my geography. I’ve lived in North Carolina for sixteen of my eighteen years, and my current home lies just twenty minutes from campus in sunny, suburban Cary, NC.

The two missing years are accounted for through my adventures in my parents’ hometown–Hyderabad, India–as a toddler. Spending some of my earliest years surrounded by a large and loving family impacted my life profoundly, forever cementing a strong connection to my emotional, cultural, and linguistic roots.

The latter had a secondary impact on me, one I wouldn’t discover until my parents enrolled me in preschool after returning to the States. With hubris, I marched into my first day of class, ready to seize the day, until I soon discovered an uncomfortable fact: I couldn’t speak English. I am told through some unfortunate stories that I struggled considerably during my first month in a new, Anglicized environment; however, I soon learned the quirks of this language, and two-year-old me, perhaps realizing that he had some catching up to do, fully immersed himself in the English language.

Nowadays, I read quite a bit. Fiction and journalism, academic and satire, I firmly believe that all styles of literature play a role in educating people on the ebbs and flows of our world. In recent years, I’ve developed a thematic fascination with the future. The genre of far-future science fiction, with its rich exploration of hypothetical advanced societies, has led me to ask pressing questions about the future of the human species. How will society organize itself politically? What are the ethical implications of future medical advancements? Will we achieve a healthy symbiosis with technology? As a Duke Research Blogger, I hope to find answers to these questions while getting a front-row, multidisciplinary seat to what the future has to offer. It’s an invigorating opportunity to grow as a writer and communicator, to have my curiosity piqued on a weekly basis, to understand the futuristic visions of innovators at the top of their field.

Prior to Duke, I had the opportunity to conduct research at the Appalachian State University Pediatric Exercise and Physiology Lab, where I co-authored a published paper about adolescent fat metabolism. Not only was I introduced to the academic research process, but I also learned the importance of communicating my findings clearly through writing and presentations. I intend to bring these valuable lessons and perspectives to the Duke Research Blog.

Beyond exercise science, I am intrigued by a diverse range of research areas, from Public Health to Climate Change to Business to Neuroscience, the latter of which I hope to explore further through the Cognitive Neuroscience and Law FOCUS. I was drawn to the program for the opportunity to build strong relationships with professors and investigators; I intend to approach my work at the Duke Research Blog with a similar keenness to listen and connect with researchers and readers alike. When I’m not reading or typing away furiously at my computer, you can find me hitting on the tennis courts, singing Choral or Indian Classical music, or convincing my friends that my music taste is better than theirs.

Post By Vibhav Nandagiri, Class of 2025

Introducing: The Duke Space Initiative

NASA

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.

Post by Zella Hanson

Invisible No More, the Cervix

How many people have seen their cervix? Obscured from view and stigmatized socially, the cervix is critical to women’s, transgender-men’s, and non-binary folks’ health — and potential reproductive health issues. A team formed through Duke’s Center for Global Women’s Health Technologies (GWHT) has created a device that not only holds immense medical potential but the potential to empower people with cervixes across the globe: It makes visible a previously invisible organ. 

Nimmi Ramanujam (Ph.D.), founder of GWHT and Professor of Engineering at Duke University, heads the team. Mercy Asiedu (Ph.D.), Gita Suneja (M.D.) Wesley Hogan (Ph.D.), and Andrea Kim have all been integral members of the interdisciplinary collaboration. Dr. Suneja is Associate Professor of Radiation Oncology at the University of Utah School of Medicine and a clinical researcher. Asiedu, former PhD student with Dr. Ramanujam and current postdoc at MIT, was integral to the development of Callascope.

The Callascope allows women and others who have cervixes, along with health professionals, to perform cervical exams without use of traditional examination tools that are larger, cannot be used for self-examinations, and often scary-looking.

When Wesley Hogan, director of Duke’s Center for Documentary Studies and research professor, heard about the idea “she was hooked.” Andrea Kim graduated from Duke University in 2018. Her senior thesis was a 12 minute documentary focused on the Callascope and its potential uses. Following graduation, over the last two years, she expanded the film to a 50-minute piece titled  “The (In)visible Organ” that was screened January 14, 2021. Kim moderated a panel with Ramanujam, Asiedu, Suneja and Hogan January 28th, 2021. 

Callascope: A handheld device that can be used to conduct cervical screenings. All that’s needed is a smart phone.

The Callascope addresses a dire global health need for better women’s reproductive health. Further, it empowers women as self-advocates of their own gynecological and reproductive health through reinvention of gynecological examination. Cervical cells have an “orderly progression,” says Suneja, we have a “great idea” of how cells become cancerous over time, “with multiple places to intervene.” Cervical examinations, however, are necessary for assessing cervical health and potential disease progression.

Originally from Ghana, Dr. Asiedu was interested in using her engineering skills to develop technology to “improve health outcomes,” particularly in countries like her own, which may lack adequate access to preventative healthcare and could benefit most from Callascope. Many women in underserved countries, as well as underserved areas of the United States, suffer disproportionately from cervical cancer — a preventable disease. 

Dr. Ramanujam, who served as a voluntary test-subject for Asiedu’s Callascope prototypes, says that it’s a really important tool “in actually changing [the cervix’s] narrative in a positive way” — it is an organ “that is indeed invisible.”

The hope is that with more awareness about and use of Callascope, cervical screenings, and vaginal health, cervixes may become more de-stigmatized and cultural norms surrounding them may shift to become more positive and open. Dr. Hogan stated that when Ramanujam pitched her the Callascope idea they were in a public restaurant. Hearing Ramanujam say words like “vagina” and “cervix” loud enough for others to hear made Hogan recognize her own embarrassment surrounding the topic and underscored the importance of the project. 

The project and the team serve as a wonderful example of intersectional work that bridges the sciences and humanities in effective, inspiring ways. One example was the Spring 2019 art exhibit, developed in conjunction with the team’s work, presented at the Nasher Museum which exposed the cervix through various mediums of art.

Multidisciplinary Bass Connections research teams contributed to this work and other interdisciplinary projects focused on the Callascope. Dr. Asiedu believes documentaries like Kim’s are “really powerful ways to communicate global health issues.” Kim who directed and produced “The (In)visble Organ” hopes to continue exploring how “we can create more cultures of inclusion …when it comes to reproductive health.” 

A piece of artwork from the (In)visible Organ art exhibit at Duke’s Nasher Museum in the spring of 2019.

Ramanujam emphasized the need to shift biomedical engineering focus to create technologies that center on “the stakeholders for whom [they] really [matter].” It is multi-dimensional thinkers like Ramanujam, Asiedu, Hogan, and Kim who are providing integrative and inventive ways to address health disparities of the 21st century — both the obvious and the invisible. 

Post by Cydney Livingston

Claire Engstrom, a Student Researcher Working to Treat Duchenne’s Muscular Dystrophy by Optimizing CRISPr-cas9

Meet Claire Engstrom, a Senior from Pasadena California. Claire is a Biology major who works in the Gersbach Lab at Duke. 

Claire first got involved with on-campus research through her pre-orientation program, PSearch that introduces incoming first-years to undergraduate research. Following her experience in PSearch, Claire got her first work-study research position in the Tung Lab where she worked closely with Jenny Tung, an Associate Professor in the Departments of Evolutionary Anthropology and Biology at Duke and a Faculty Associate of the Duke University Population Research Institute. 

In the Tung Lab, Claire’s research focused on how DNA methylation is passed through generations. Essentially looking at the inheritance of DNA whose methylation was impacted by environmental factors and how that affects future generations. 

Duke has research opportunities available in all disciplines as well as across departments. Approximately 53% of undergraduates graduate with research experience. Not only can students participate in groundbreaking research, but they can receive funding from the university as well to support the work they are doing.

Within the Biology department, there is a fellowship called B-SURF, the Biological Sciences Undergraduate Research Fellowship, an 8-week summer research program for rising sophomores. Claire applied for and was accepted to the fellowship and placed in one of Duke’s biomedical science laboratories. She also received a $4,000 stipend for her summer research.

Claire was placed in Charles Gersbach’s Lab focused on researching Genome Editing for Gene and Cell Therapy. Dr, Gersbach is a Rooney Family Associate Professor of Biomedical Engineering and has conducted groundbreaking work in genome editing.

Members of the Gersbach Lab in Fall 2019

Gersbach is doing research in several different domains of biomedical engineering. Claire’s project focuses on using CRISPR-Cas9, a technology that allows scientists to change an organism’s DNA using clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. faster, cheaper, more accurate, and more efficient than other existing genome editing methods. 

Prior to joining his lab, Claire had already heard a lot about Gersbach in her course Biology 201 as well as through reading his papers. The project she would spend the next two and a half years working on focused on using and optimizing CRISPR-Cas9 to treat Duchenne’s Muscular Dystrophy and lessen the severity of the symptoms. 

Duchenne’s Muscular Dystrophy is a muscle wasting disease that affects one in every five thousand male births.

“People are diagnosed when they are around five and then they lose the ability to walk and their heart can’t pump blood because of the lack of muscles.” Claire explained.  

“CRISPR-based genome editing restores dystrophin expression in mouse models of Duchenne muscular dystrophy. Cross-sections of muscle tissue where the dystrophin protein has been labeled green, including normal, healthy tissue (left), tissue from a mouse model of Duchenne muscular dystrophy (middle), and tissue from the same mouse model that has been treated with the CRISPR gene editing system (right). Nelson et al., Science (2016)”

Thus, those affected often die in early adulthood despite current advances in cardiovascular and respiratory treatments. Duchenne’s Muscular Dystrophy generally occurs as a result of a frameshift mutation of the dystrophin gene. As a result, one’s muscles can no longer connect to anything making it nearly impossible to contract and function properly. In the Gersbach lab they are trying to treat the mutation by using CRISPR-Cas9 to remove an exon or coding region of the gene in order to shift the reading frame back into its normal place. 

This shift produces a less severe phenotype that lessens the effects of Duchenne’s Muscular Dystrophy. The result will significantly improve the quality of life and life spans for affected patients. 

Claire will be continuing her work in the Gersbach lab full time in Spring 2021 as she graduated early, with distinction in the Fall. Her thesis on the work she did in the Gersbach lab was recently approved and her results will be published in a larger paper in the future. After this year she plans to take a gap year an then return to California to hopefully attend grad school and pursue a Ph.D. in Biology.

By Anna Gotskind

Duke’s Fundamental Research Can Turn Viruses Into Marvels

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
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
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.
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

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