Computation and crochet
Photos by Evan Krape and courtesy of Jodi Hadden-Perilla May 24, 2023
91原创 Professor Jodi Hadden-Perilla to use NSF Award for virus studies, assistive technology for the blind, crochet for all
Viruses are a strange lot indeed. They possess baffling adaptive abilities, know how to hijack healthy cells and have the power to bring global economies to their knees. We鈥檙e looking at you, COVID-19.
Understanding how viruses work and how they might be rendered innocuous or pressed into submission to accomplish beneficial work is a high-value quest for scientists.
That鈥檚 the kind of research Jodi Hadden-Perilla, assistant professor of chemistry and biochemistry at the 91原创, is doing.
Now she is doing it with the support of the National Science Foundation, which selected her for a 2023 CAREER Award. The award recognizes the promise of the work she has proposed and brings five years of funding totaling $800,000. The project is funded jointly by NSF鈥檚 Division of Molecular and Cellular Bioscience, Molecular Biophysics Program and the Established Program to Stimulate Competitive Research (EPSCoR).
Hadden-Perilla brings extensive computational expertise to this research. And she brings innovative approaches to her work as an educator, mentor and science communicator.
Understanding viruses demands that sort of prowess.
鈥淰iruses are wild and creepy,鈥 she said. 鈥淭hey鈥檙e shapeshifters. They manipulate the host cell. They respond to chemical signals, almost like they make decisions.鈥
They鈥檙e tough to understand, in other words. And they are fascinating. She wants others to have the opportunity to experience that fascination.
So her research plan includes three projects to expand the reach and impact of the work:
It includes development of tactile software for blind students to use.
It includes proving to mathematics-averse students that they can learn how to incorporate calculations into their work and discover how those computations will guide, enhance and expedite future research.
And it includes the use of crochet to help illustrate the structure of viruses and their components for non-scientists.
The science
Hadden-Perilla focuses on two viruses in this research 鈥 Hepatitis B, which attacks the human liver, and Brome mosaic virus (BMV), which attacks cereal crops, such as wheat, rice and oats.
Specifically, she is investigating how these viruses use a common biological process called phosphorylation to change their shape and accomplish their objectives, such as packaging their genetic material and infiltrating the host cell鈥檚 nucleus or other critical component.
In these two viruses, the phosphorylation process happens when phosphate groups are joined to proteins known as 鈥渋ntrinsically disordered鈥 proteins. The negative charge of the phosphate groups changes the charge of the proteins and that change allows the virus to change its configuration.
鈥淲hen you think of proteins you think of them having a nice fold and shape,鈥 she said. 鈥淪ome proteins do not have that 鈥 they are intrinsically disordered, like spaghetti wiggling around being all messy. They are very interesting systems. Intrinsically disordered proteins are like a Swiss Army knife that adopt several different shapes that do different things.鈥
These processes are not well understood, though. Once these phosphorylation patterns and effects are better known, scientists can focus on how those processes can be interrupted or manipulated in other ways.
Essentially, Hadden-Perilla is aiming to take the virus machine apart, understand what each piece does, then put it back together. An important part of that work 鈥 the structure of these intrinsically disordered shapes 鈥 is missing, though.聽
鈥淲e鈥檙e trying to rebuild a missing piece,鈥 she said. 鈥淲e don鈥檛 know exactly what it looks like. We know what it should do. And we want to put every atom back in place.鈥
All of this is done with a virtual microscope, not the kind usually found in a biology lab or microscopy center.
Rather, she uses what she describes as the only instrument capable of characterizing these dynamic molecules and the functions they make possible 鈥 the computational microscope, powered by supercomputers.
With a better understanding of these virus machines, new possibilities arise. A proverbial wrench could be thrown into the virus鈥檚 works, preventing its sinister plans. Or perhaps the actions of the virus could be turned toward something useful, so that their properties may be used in constructive ways. Scientists have reported the use of viruses as nanoreactors and cargo delivery systems.
The instruction
Hadden-Perilla is not content for this exciting research to be unavailable to anyone.
Part of her plan for the project includes developing tactile software to help blind students learn how to do computational biophysical chemistry.
She has already proven that concept, thanks to a former student, Olivia Shaw, who worked in Hadden-Perilla鈥檚 group for a while. Shaw now is preparing for law school, aiming to concentrate in health science law, but said the experience in Hadden-Perilla鈥檚 lab equipped her well for the future.
鈥淢aking this type of work accessible was a novel experience for both of us,鈥 Shaw said. 鈥淣ot only did I learn so much about virology, computational chemistry and scientific presentation, but I also learned how to advocate for myself in a collaborative way鈥. The skills that I learned in Dr. Hadden-Perilla鈥檚 lab have prepared me well for a career that centers around advocacy, presentation and the ability to quickly adapt to new situations and learn new skills. While I do not plan to pursue scientific research in the future, I will be a lifelong advocate for those disabled people who do enter the field.鈥
Finding a mentor such as Hadden-Perilla is essential, Shaw said.
鈥淭he most important thing any student can do when they are interested in research is to find a great mentor,鈥 she said. 鈥淭his is doubly true if the student is disabled. I was grateful that Dr. Hadden-Perilla worked with me to make the research process as accessible to me as possible. It took immense amounts of work on both of our parts, but I think it was worth it.鈥
Hadden-Perilla wants to draw more undergraduate students into research 鈥 even those who are not interested in mathematics 鈥 by developing modules for undergraduate courses that give students hands-on experience with computational biophysics.
And finally, she wants to expand a unique outreach of her lab 鈥 the use of crochet to illustrate components of viruses.
She started making crochet items during graduate school. Then, after meeting the man who would later be her husband 鈥 Juan Perilla 鈥 at the University of Illinois-Champaign 鈥 she made a crochet model of the HIV capsid for his birthday.
After the couple joined the 91原创 faculty, she found another student who enjoyed crochet and that student took up the cause.
鈥淚鈥檝e got some crazy ideas that I think will help bridge the gap for some people,鈥 Hadden-Perilla said.
The journey
Tab Hadden, a blue-collar construction worker from Metter, Georgia, couldn鈥檛 have known where his daughter would invest her considerable intellect. But he recognized great potential and wanted her to get the best education possible and go as far as she wanted to go with whatever it was she wanted to study.
He didn鈥檛 know what that would take. He grew up working on a farm. Jodi鈥檚 mother, Lesia, grew up in government housing.
But they would make it possible, he said.
鈥淵ou鈥檙e smart,鈥 her dad told her. 鈥淵ou can do it and I want you to go to college. I鈥檓 going to make this possible. I鈥檒l find a way to do it. You have to do your part. You have to work very hard and hold up your end of the deal.鈥
This commitment provided powerful fuel.
鈥淗e brainwashed me with this conversation and I became very focused on school,鈥 Hadden-Perilla said.
She was the valedictorian in a graduating class of 74 students and got a scholarship to Georgia Tech.
There, she hit a hard wall. She failed calculus in her first semester and passed her chemistry class with a 鈥淐.鈥
鈥淚t was partly culture shock,鈥 she said. 鈥淚 was in the big city now and everything I knew how to do to be successful in school just didn鈥檛 work anymore.鈥
She was staggered by all three semesters.
鈥淚n my last semester at Georgia Tech, I failed all my classes but marching band,鈥 she said recently, with a smile. 鈥淚 was in over my head.鈥
Science and math were chewing her up.
鈥淭o my family鈥檚 immense credit, my family never discouraged me,鈥 she recalled. 鈥淢y dad said, 鈥楤aby, we know you tried hard. Daddy couldn鈥檛 have done it.鈥欌
Despite those struggles, she didn鈥檛 give up.
鈥淚t never occurred to me to stop college,鈥 she said. 鈥淚t just occurred to me that we had to do something different.鈥
She transferred to Armstrong Atlantic State University, now a satellite campus of Georgia Southern, and found her footing again.
鈥淚t was primarily an undergraduate school with smaller class sizes,鈥 she said. 鈥淚 had more time with faculty and it saved me.鈥
She excelled in classes that had stymied her just a year before, did some undergraduate research and started getting interesting suggestions from mentors.
鈥淵ou should consider graduate school,鈥 they told her.
She went to the Southeastern regional meeting of the American Chemical Society and met lots of people from graduate schools.
She ultimately applied to the University of Georgia and worked with Robert Woods in the Complex Carbohydrates Research Center, studying the molecular dynamics of carbohydrates.
Just before she started grad school, her father was diagnosed with cancer. He died in December 2013, about four months before she defended her doctoral dissertation.
鈥淚 spent graduate school watching him die,鈥 she said, 鈥渁nd that was hard. An essential aspect of all of this for me was that Daddy told me to do it, then he didn鈥檛 get to see me finish it.鈥
She has done him proud, though.
From Georgia she went to the University of Illinois Urbana-Champaign, where she worked with Klaus Schulten at the Beckman Institute. That鈥檚 when she started working on viruses 鈥 including a crocheted model she made to celebrate the birthday of Juan Perilla, who was studying viruses, too, and had become her partner.
When Perilla was appointed to the faculty of the 91原创 in 2017, 91原创 offered Jodi a postdoc position and a two-year contract. A year into that work, Juan proposed marriage and the next year Hadden-Perilla joined 91原创鈥檚 faculty in chemistry.
Together and separately, they have done extraordinary work on viruses including HIV, Ebola, COVID-19 and hepatitis.
Hadden-Perilla said a silver lining from the difficult days at Georgia Tech was a requirement that chemistry majors spend a semester learning to code.
鈥淓verybody told me this class was really hard,鈥 she said. 鈥淏ut there might be boys who could help you with your homework.鈥
She loved the class, wound up helping the boys with their homework, took more programming classes after transferring to Armstrong and started thinking about computer science as a focus instead of chemistry.
Her adviser told her to go home and look up computational chemistry.
It was pivotal advice.
She and Juan have since worked on some of the best supercomputing machines in the United States, she said 鈥 including Blue Waters, Comet, Bridges, Anton 2, Summit and Frontera.
Tab Hadden pointed her in the right direction and Hadden-Perilla has made the most of it.
鈥淭here鈥檚 a wide range between where I am in my understanding now and where I would be if I hadn鈥檛 gone to college,鈥 she said. 鈥淎nd now I think of ways we might explain structural biology to those who find it intimidating. It鈥檚 really neat and we have to make it approachable to people.鈥
She contributes to communicating science in many ways, including service as social media editor for the Journal of Structural Biology, Current Opinion in Structural Biology and Current Research in Structural Biology.
鈥淪cience looks scary from the outside,鈥 she said, 鈥渂ut there are ways we can include the public in science and educate the public. We as scientists can do more to share our passion and love of what we do with the public.鈥
Contact Us
Have a 91原创aily story idea?
Contact us at ocm@udel.edu
Members of the press
Contact us at mediarelations@udel.edu or visit the Media Relations website
