Portraits of Dominik Konkolewicz and Rick Page flank an image of coronaviruses.

Two Miami University researchers receive NSF RAPID grant to develop coronavirus-attacking materials

Materials will help limit indirect contact transmission of COVID-19

Two Miami University researchers in protein, polymer and materials chemistry received a Rapid Response Research (RAPID) grant from the National Science Foundation (NSF) for a project that will address the spread of the novel coronavirus.

They received $181,849 to develop materials that can be used to prevent indirect contact transmission of the SARS-CoV-2 coronavirus responsible for COVID-19.

Dominik Konkolewicz and Rick Page, both associate professors of chemistry and biochemistry, are the primary and co-investigators of the project.

Reduce indirect contact transmission of COVID-19

The virus responsible for the COVID-19 pandemic is especially concerning for indirect contact transmission, since it can remain active on various surfaces for extended periods of time, Konkolewicz said.

If a person infected with COVID-19 deposits active viral particles (droplets or aerosols) on frequently touched surfaces, the disease can be transmitted if an uninfected person picks up the active viruses from the contaminated surface.

In this way, the disease can be spread even if the two individuals do not ever come in direct contact with each other. Since the virus can remain active on surfaces for days, there is an increased risk of indirect contact transmission.

To help limit this, Konkolewicz and Page will develop materials that can capture and inactivate the coronavirus on surfaces.

Capture and inactivate the virus

Through their work in synthetic polymer chemistry and protein chemistry, the researchers plan two complementary approaches in developing coronavirus-attacking materials:

Inactivate: One approach is to disrupt the lipid layer/lipid envelope in the coronavirus. This lipid envelope is critical to the structure of the virus and also to its infection mechanism. “If we disrupt the lipids, we can inactivate the coronavirus, such that it cannot infect a new individual,” Konkolewicz said. (Handwashing with soap is one example of disrupting the lipid layer to inactivate the virus).

Capture: The other approach is to capture and trap the coronavirus spike proteins within the synthetic material. This way the virus cannot leave and provide a path for a new infection.

Combined: The researchers will also develop materials with both capture and inactivation capabilities. This two-pronged approach tethers the virus to the surface to allow for increased opportunities to attack and inactivate it, Page said.

The new materials they develop could be adapted or coated onto existing high touch surfaces to limit indirect contact transmission, Konkolewicz said. The polymers will form a tough network to ensure the material performs for an extended period of time.

Konkolewicz and Page will also develop content on the importance of polymer materials in healthcare applications. This will be distributed through YouTube channels for accessibility to the public.

About the researchers

Konkolewicz researches responsive, or “smart” polymer materials and materials that contain both synthetic and biological components. He was awarded an NSF CAREER Award for self-healing polymers in 2018. He was named a 2018 Young Investigator by the American Chemical Society-Polymer, Materials Science, and Engineering section and he received the 2018 Polymer Chemistry Emerging Investigator Award. He and his research team have multiple research collaborations with colleagues in chemistry, biochemistry, chemical engineering and mechanical engineering. He was named a Miami University Junior Faculty Scholar in 2018.

Follow Konkolewicz on Twitter @PolyKonkol.

Page researches the structure, dynamics and mechanisms of action for proteins in a range of biologic and synthetic systems. He was named a Miami University Junior Faculty Scholar in 2016. He received an NSF Career grant in 2016 for his research on protein quality control. In 2018 he received a five-year MIRA (Maximizing Investigator’s Research Award) — one of Miami’s first two — that supports his research projects on protein quality control and antibiotic resistance. He has multiple research collaborations with colleagues in chemistry, biochemistry and bioengineering.

Follow Page on Twitter @ThePageLab.

NSF RAPID grants

The grant for “RAPID: Viral Particle Disrupting and Sequestering Polymer Materials applied to Coronaviruses,” will support the research of Page and Konkolewicz for one year and support three graduate students.

RAPID grants give the NSF a way to help fight the pandemic by supporting scientists doing relevant work across many disciplines, according to the foundation. They may be funded for up to $200,000 and up to one year in duration, with an average award size of $89,000.

In March Congress gave NSF an extra $75 million in the CARES Act stimulus funding to spend on research projects that will help “prevent, prepare for, and respond” to the novel coronavirus.


Written by Susan Meikle, Miami University News and Communications. Originally appeared as a “Top Story” on  Miami University’s News and Events website.

Photos of Dominik Konkolewicz and Rick Page by Miami University Photo Services. Image of coronaviruses by By U.S. Army. Public domain.

Ellen Yezierski in her lab.

$1.9M NSF grant will help teachers stimulate students’ imaginations to improve learning of chemistry

A water molecule, H2O. Liquid water, H2O(I). Covalently bonded molecules held together by intermolecular hydrogen bonds.
An example of the VisChem dynamic visualizations.

With a new $1.9 million grant from the National Science Foundation, Miami University’s Ellen Yezierski aims to help high school chemistry teachers prepare students to become more scientifically literate.

Her project has the potential to impact up to 80,000 high school chemistry students from a broad range of socioeconomic, geographic and racial backgrounds, Yezierski said. It will focus on traditionally underserved groups, including English language learners.

Yezierski, a chemistry education researcher, was awarded the five-year grant for her design research in the teaching and learning of high school chemistry through the use of dynamic visualizations — “VisChem” molecular animations designed by Roy Tasker.

These video animations of the molecular world can bring a new dimension to learning chemistry.

The project will develop teachers’ knowledge and skills to help their students build molecular-level mental models to explain chemical events, Yezierski said.

Currently, chemistry education overemphasizes description and symbols rather than learning to explain chemical phenomena.

Students becoming informed adults for a changing world

Yezierski will recruit 64 high school chemistry teachers from across the country to participate in the professional development program.

They will learn how to effectively use storyboarding and the VisChem approach to lead students from describing chemical phenomena, such as reactions and physical changes, to understanding and explaining their causes.

One goal is to help high school students become more scientifically literate. The focus is on learning how to reason with chemistry concepts and principles, rather than on memorizing facts, Yezierski said.

Ultimately, students will be better prepared to understand science in areas requiring molecular-level perspectives, and to become informed adults in a changing world, Yezierski said. Some areas include understanding the role of carbon dioxide in climate change, changes in DNA in genetically modified organisms (GMOs), antibiotic resistance and drinking water quality.

VisChem Institutes: Molecular animations, storyboarding for understanding

An example of the VisChem dynamic visualizations. The images from video animations of liquid water (above) and boiling water (below) show differences in molecular activity of different physical states of water (images by Roy Tasker from VisChem.com.au).
Three teacher cohorts — one cohort each over the next three summers — will attend the all-expenses-paid VisChem Institute (VCI) on campus developed by Yezierski.

The institutes will be taught by Yezierski and project consultant Roy Tasker, creator of the VisChem dynamic animation system. “Animations of the molecular world can stimulate the imagination, bringing a new dimension to learning chemistry,” Tasker said.

For instance, few students have a “feel” for the average distance between ions (charged particles) in a solution of a given concentration, according to Tasker.

“VisChem animations of ionic solutions bring meaning to the magnitude of the number expressing molarity (concentration of a chemical in solution), in much the same way that people have a ‘feel’ for the length of one meter,” Tasker said.

Design research: Supports teachers’ learning

Yezierski’s design research involves studying how to support teacher groups in learning chemistry content and instructional methods.

Teacher cohorts will be supported during the following year after they attend the VCI. Some will be provided with software to run their own molecular simulations. Eventually all teachers will develop and grow a community of skilled practitioners using the VisChem approach.

In their classrooms, teachers will wear tiny GoPro cameras to collect video clips of their teaching. The clips will provide data about what teaching methods are more effective than others.

Those clips will be studied and evaluated by Yezierski and her team to inform and improve the design of future VCIs and improve chemistry teaching with molecular visualizations.

The time is right

Yezierski has been conducting chemistry education and teacher professional development research for the past 16 years. She is nationally recognized for conducting groundbreaking research that improved instruction and student learning as a direct result of Target Inquiry, a visionary professional development model for high school chemistry teachers.

She has a long history with Tasker, having based her doctoral dissertation research on the use of VisChem dynamic visualizations.

She has recently started to see chemistry teachers become more open to/interested in incorporating dynamic visualizations and storyboarding in their teaching.

This approach aligns with the newest Next Generation Science Standards and the recently updated AP chemistry curriculum, Yezierski said.

The team

Yezierski, professor of chemistry and biochemistry, is also director of Miami’s Center for Teaching Excellence.

She was named an American Chemical Society Fellow in 2016.

An experienced high school chemistry teacher, she taught chemistry for seven years before earning her doctorate from Arizona State University in 2003.

Her research team will include a postdoctoral fellow, two graduate students, several undergrad students and Tasker.

Tasker is a renowned Australian chemistry education researcher. He received the Prime Minister’s Award for Australian University Teacher of the Year in 2011 and the prestigious Australian National Senior Teaching Fellowship in 2014.

He created the VisChem approach in the 1990s, and since then the dynamic visualizations have been adopted by educators and textbook authors internationally.


Written by Susan Meikle, University News Writer/Editor, University Communications and Marketing, Miami University. Originally appeared as a “Top Story” on Miami University’s News and Events website.

Photo of Ellen Yezierski by Jeff Sabo, Miami University Photo Services. VisChem dynamic visualization by Roy Tasker from VisChem.com.au.

 

Dominik Konkolewicz helps a student in the classroom. Part of a periodic table is visible in the background.

Dominik Konkolewicz receives CAREER Award from the National Science Foundation

Dominik Konkolewicz and a student work with some equipment in Konkolewicz's lab.
Dominik Konkolewicz (right) has been awarded an NSF CAREER grant in support of his polymer research.

Almost everyone has experienced the disappointment that comes along with the first scratch on a new car, a freshly painted wall, or a just-out-of-the-box cell phone. But what if that scratch were just a temporary thing? What if the car or wall or phone could repair itself and no one would ever know the scratch had been there? If Dominik Konkolewicz has anything to do with it, that fantasy may one day become reality.

Konkolewicz, an assistant professor of chemistry and biochemistry at Miami University, recently received a CAREER grant from the Faculty Early Career Development program of the National Science Foundation (NSF).

The NSF CAREER grant is one of the organization’s most prestigious awards in support of junior faculty who “exemplify the role of teacher-scholars through outstanding research, excellent education, and the integration of education and research within the context of the mission of their organizations.”

Konkolewicz is the ninth scientist at Miami to be awarded a CAREER grant. He and his group will receive $600,000 of funding over five years for his research program on polymers. This award brings the number of currently active CAREER grants at Miami to two.

“If you look around a room, and you remove the air, metals, ceramics, and the small amount of water, just about everything else is a polymer,” Konkolewicz says.

Polymers can be natural or synthetic. Natural polymers include cellulose, which is the main component of wood and paper, and proteins or DNA that are essential for life processes. Among the dozens of commodity synthetic polymers are polyethylene milk jugs and plastic wrap; polystyrene packing materials; polyvinylaacetate (PVA) and epoxy glues; and PET soda and water bottles. Polymers are also included as components of paints and other coatings used to finish surfaces like those of cars, walls, and cell phones.

From a chemistry perspective, polymers consist of smaller molecules, or repeating units, linked together to form a larger molecule. This larger molecule, or macromolecule, is like a necklace, with dozens to tens-of-thousands of smaller molecules making up the individual links. In many useful materials, such as cured epoxy glue, soft contact lenses, and the rubber used in tires, long polymer chains are linked to form a mesh or network-like structure at the molecular level.

“The links that bind these chains together are a little like staples,” Konkolewicz says. “They’re permanent. When a material becomes damaged or fractured, the material becomes useless because there’s no way to recover the original properties.”

Konkolewicz’s work focuses on creating links between the chains that he says are more like paper clips than like staples, ones that can be reused many times. If one link is damaged, it can be exchanged for another one, allowing the material – whether it’s wall paint or a truck tire – to heal itself when scratched or punctured.

Konkolewicz says the tradeoff in this kind of chemistry, since it was pioneered in the late 1990s and early 2000s, has been between dynamism and stability. The types of “paper clips” used to hook units together would either allow a material to recover its original properties very quickly, or allow it to maintain its original shape over time, but typically not both.

To understand this tradeoff, we can think about truck tires. If they were made out of a material that could heal quickly when punctured by a nail picked up on the road, drivers could avoid the time, expense, and hassle of being stuck with a flat. However, if that same highly dynamic material were also highly unstable, the tires would lose their shape as they were squeezed between the truck and the road. That’s exactly the dilemma Konkolewicz says currently exists in this type of materials science.

His innovation is to introduce two different types of links in the same material. One type of link would allow the material to heal itself quickly, while the other – which would be activated by applying heat, pH, or light – would “lock in” the permanent shape. In the case of truck tires, that means they could both recover from a nail puncture and remain perfectly round.

Another consideration Konkolewicz says is important in materials science is toughness, or the ability to withstand seemingly minor damage. Once a brittle material acquires a small chip or other defect, any little bump could cause it to shatter. Konkolewicz says the types of dynamic bonds that he is using can increase material toughness, extending the useful lifetime of products made from those materials.

Konkolewicz’s work has clear implications for sustainability. “If you don’t need to throw something out over time, if something has a longer lifetime, that’s a huge benefit,” he says. “It’s a much smaller drain on resources.”

Konkolewicz currently supervises eight graduate students and has 11 undergraduates on his team. He has also mentored an additional graduate student who has since graduated. These students work with Konkolewicz on his CAREER project, as well as on his other projects involving conjugation of synthetic materials to enzymatic proteins and development of light driven chemical and polymerization processes.

All NSF CAREER projects include an integrated education objective. Konkolewicz will conduct community-based STEM outreach for K-12 students in collaboration with Dayton Public Schools and the Public Library of Cincinnati and Hamilton County. In addition, he will continue developing innovative activities to use in the undergraduate classroom. For example, he plans to expand a pilot project in which students use YouTube as a forum to reflect on how they overcame challenges in their studies and to share these strategies with their peers. The CAREER grant will also provide funds for a student from underrepresented groups to work in Konkolewicz’s lab each summer.

Konkolewicz received his doctorate from the University of Sydney in 2011 and was a visiting assistant professor/senior research chemist at Carnegie Mellon University from 2011 to 2014.


Written by Heather Beattey Johnston, Associate Director of Research Communications, Office for the Advancement of Research and Scholarship, Miami University.

Photos by Jeff Sabo, Miami University Photo Services.

Scott Hartley and grad student Zach Kinney work with a piece of equipment in Hartley's lab.

Scientist affirms the power of serendipity and human curiosity in research

Dr. Scott Hartley and three graduate students work with equipment in Hartley biochemistry lab.
Dr. Scott Hartley (in suit jacket) received an NSF grant to study the tertiary structure of ortho-phenylenes. Also pictured, from back to front, are graduate students Lasith Kariyawasam, Zach Kinney, and Gopi Nath Vemuri.

In a June 2015 post on the White House blog, Associate Director for Science at the White House Office of Science and Technology Jo Handelsman wrote, “One of the hallmarks of science is that the path to knowledge is often indirect, and that in addition to rigorous investigation, discovery is often shaped by serendipity [and] human curiosity.” That’s certainly true for Miami University professor of chemistry and biochemistry Scott Hartley. His curiosity turned an early-career failure into a new line of research.

When he first came to Miami University, Hartley and his colleagues were working with a class of molecules called ortho-phenylenes as precursors to new molecules that could be used in nanomaterials. But no matter what they tried they couldn’t make it work. Meanwhile, they had become intrigued by an unusual behavior they had observed in the ortho-phenylenes themselves: they fold into helices, or three-dimensional corkscrew-shaped structures.

ortho-Phenylenes are not unique in their folding; Hartley says there are many classes of so-called foldamers, and that, like ortho-phenylenes, many of them fold into helices.

“When nature wants to produce very complicated, large molecules,” Hartley says, “it does that by essentially taking a string and folding it into a complicated shape as a way of generating complexity while minimizing how difficult it is to chemically construct the molecules. It’s like origami.”

The unusual behavior Hartley and his colleagues observed was not the folding itself, but how slowly ortho-phenylenes do it, compared to other foldamers. Just like slow-motion video replays allow athletic officials to see more accurately what happened on the field or the court, the relatively slow-motion folding that occurs in ortho-phenylenes allows Hartley to see more accurately what happens during molecular folding.

“We just stumbled into this really useful system that turns out – through no clever design – to have some really unique features that we can exploit,” he says, echoing Handelsman’s sentiment about the serendipity of discovery. “The project sort of evolved on its own and we just sort went where it took us.”

Where the project ultimately took Hartley is to an investigation of the tertiary structure of ortho-phenylenes. With the support of a $430,000 grant from the National Science Foundation (NSF), Hartley is currently working to figure out how to manipulate the position of foldamer molecules relative to each other in space. This, he says, is the key to building larger, more complex molecules that could one day be used to develop new catalysts or new molecular-recognition sensors.

The work is time-consuming. Hartley says there is a lot of organic synthesis required to create the systems he’s working on and a lot of characterization – often in the form of nuclear magnetic spectroscopy – that goes into understanding the behavior of these molecules. It’s all part of the “rigorous investigation” Handelsman alluded to in her blog post, and Hartley is grateful for the undergraduate and graduate students who help him accomplish it.

“The undergrads are really an important part of the project,” he says. “They work really closely with the graduate students to do a lot of that work. The graduate students are intimately involved in their training, standing next to them in the lab and answering their questions.”

It’s possible some of those questions might be about things that don’t necessarily seem relevant to the current project. But Hartley would probably be the first to point out the potential those questions hold.

“If I did anything smart along the way,” this veteran scientist says, “it was recognizing something interesting and deciding just to run with it.”

And to that we say, “Run on, Scott Hartley. Run on.”


Written by Heather Beattey Johnston, Associate Director of Research Communications, Office for the Advancement of Research and Scholarship, Miami University.

Photos by Jeff Sabo, Miami University Photo Services.

Assistant professor of chemistry, Rick Page, works in a lab with undergraduate student Chanell Upshaw.

Professor of chemistry and biochemistry receives NSF CAREER award

Head-and-shoulders portrait of Rick Page
Rick Page

Rick Page, assistant professor of chemistry and biochemistry at Miami University, has been recognized as one of the nation’s top young faculty in his field by the National Science Foundation (NSF) with the award of a CAREER grant from the NSF Faculty Early Career Development Program.

The NSF CAREER grant is one of the organization’s most prestigious awards in support of junior faculty who “exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organizations.”

Page is the sixth scientist at Miami to be awarded a CAREER grant.

He will receive more than $920,000 of research funding over five years for his research program on the biological regulation of quality control in proteins.

“Protein quality control is a fascinating process taking place in all of our cells,” Page said. “It is a fundamental process of repair that allows us to respond to stress and renew the machinery of life.”

The three-dimensional structures of proteins determine the roles and functions proteins play within cells, Page said. Exposure to chemical or mechanical stresses can cause proteins to misfold, resulting in large changes in three-dimensional structure and loss of protein function.

To survive, cells have developed quality control systems that guide misfolded proteins towards pathways that lead to them either being repaired or discarded.

Page’s research project will help determine the biological principles that allow cells to respond to protein misfolding by directing misfolded proteins for destruction.

Page has established a large research group since he joined Miami in 2013. He currently mentors three doctoral students and 13 undergraduates. He has also mentored six other undergraduates who have since graduated.

His CAREER project includes an integrated education objective that aims to increase retention of underrepresented students in STEM (science, technology, engineering and math) through direct outreach at the high school and undergraduate levels.

“Advancing education is at the core of our efforts at Miami and is integrated throughout the grant,” Page said.

He seeks to “provide experiential learning opportunities for undergraduate students with the goal of enriching their hands-on knowledge of biochemistry and biophysics.”

His core research focuses on the molecular interactions and mechanisms that govern protein quality control carried out by a complex of two proteins: CHIP and Hsp70.

The CAREER project will redefine how the protein quality control field views the role of interactions between Hsp70 and CHIP in regulating how cells respond to protein misfolding.

Using a combination of research methods — NMR (nuclear magnetic resonance), SAXS (small-angle X-ray scattering) and EPR (electron paramagnetic resonance spectroscopy) with biolayer interferometry — Page will also generate advances in the use of hybrid methods for structural biology.

Page was recently named a Miami University Junior Faculty Scholar.

He has multiple research collaborations with colleagues in chemistry and biochemistry and in bioengineering and has secured more than $1.6 million in external research funding since he joined Miami, including an American Heart Association Scientist Development Award.

He also receives excellent reviews on the courses that he teaches at Miami, according to those who nominated him for the Junior Faculty Scholar award.

Page received his doctorate from Florida State University in 2008 and was a postdoctoral research fellow at the Cleveland Clinic from 2008 to 2013.

Other Miami scientists who have received NSF CAREER grants include:

  • Rachel Morgan-Kiss, associate professor of microbiology, 2011
  • Hong Wang, associate professor of chemistry and biochemistry, 2011
  • John Karro, associate professor of computer science and software engineering, 2010 (no longer at Miami)
  • Mike Brudzinski, professor of geology, 2009
  • Janet Burge, associate professor of computer science and software engineering, 2009 (no longer at Miami)

Written by Susan Meikle, University News Writer/Editor, University News & Communications, Miami University. Originally appeared as a “Top Story” on Miami University’s News and Events website.

Photos by Scott Kissell, Miami University Photo Services.

A photograph of a stick-and-ball model. The balls are either red, yellow, black, white, or blue and the sticks are metal.

$1M+ NSF grant supports development of assessments to improve chemistry education

Three models -- one an illustration and two 3D stick-and-ball -- are shown.
Models like these, which represent chemical bonding, are often used to teach basic chemistry concepts to students.

In response to projections that the U.S. will need an additional one million workers in science, technology, engineering, and math (STEM) by 2022, the President’s Council of Advisors on Science and Technology (PCAST) issued a report in 2012 that called for improving STEM education during the first two years of college.

Having spent her career researching the teaching, learning, and assessment of chemistry, Dr. Stacey Lowery Bretz, Miami University’s Volwiler Distinguished Research Professor of Chemistry, knows just how important those first two years are.

“Fewer than 40% of the students who start out majoring in a STEM field stick with it,” Bretz says.

Even students who did well in high school science classes can struggle in – and fail or drop out of – introductory-level classes in college. While in the past this attrition was accepted as a necessary “weeding out” of weaker students, the current emphasis on STEM education means faculty must reconsider their role in student learning. According to Bretz, “There’s growing recognition among science faculty that we need to do a better job teaching basic concepts.”

In Bretz’s field of chemistry, basic concepts center on understanding the structure and properties of matter. “To teach students about molecules, compounds, atoms, and ions, we use models or representations of these things,” Bretz says, “but the way students interpret our representations often leads them to develop misconceptions about the concepts we’re trying to teach.”

So, backed by a $1.28 million grant from the National Science Foundation (NSF) – her second $1 million-plus grant since coming to Miami in 2005 – Bretz is embarking on a 5-year project to assess how students interpret representations of core chemistry concepts.

One goal of the project is to develop assessment tools that other chemistry instructors and chemistry education researchers can use to gather data on their own students’ learning. Then, Bretz and her team, including a post-doctoral fellow and four graduate students, will hold workshops to teach their colleagues how to use the tools and how to properly analyze the data they yield.

“Evidence-based instructional practices are very important,” Bretz says. “But, we have to create measurement tools to establish baseline data on learning first.” From there, researchers will be able to tell whether future innovations in pedagogy and curriculum are effective at moving the needle on student retention. And that, she reminds us, is key to answering PCAST’s call to improve STEM education.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University

Featured image (left) used under Creative Commons license, courtesy of Flickr user Charles Clegg.  Other images (above) courtesy of Stacey Lowery Bretz.

A graphic representation of the KCNQ1 protein. Two parallel corkscrew shapes are arranged on a black background. The shapes are rainbow colored.

Team lays groundwork for developing treatment of cardiac disorder

Four graduate students and a postdoctoral researcher pose with equipment they use to conduct research
Members of professor Gary Lorigan’s research team include (from left to right): graduate student Andrew Craig, postdoctoral researcher Dr. Indra Dev Sahu, and graduate students Lauren Bottorf, Dan Drew and Afu Zhang. Not pictured are graduate student Lishan Liu and undergraduate students Megan Dunagan, Raven Comer, Kunkun Wang, and Avnika Bali.

 

“Scared to death,” is more than a hyperbolic phrase to sufferers of long QT syndrome (LQTS); it’s a very real possibility. In LQTS, exercise and unexpected noise – like the ring of a doorbell or the backfire of a car engine – can set off potentially fatal heart arrhythmias in otherwise healthy children, teenagers, and young adults. It may even be a cause of sudden infant death syndrome (SIDS).

Most cases of LQTS are the result of inherited genetic mutations. But while scientists have identified a number of genes associated with LQTS, the mechanism by which mutations in these genes affect the electrical system that controls the heart’s rhythm is not well understood. As a result, the development of medical treatments for the disorder has been limited.

Gary Lorigan wants to change that. A professor in Miami’s Department of Chemistry & Biochemistry, Lorigan is working to describe the structural and dynamic properties of proteins produced by two genes implicated in LQTS: KCNE1 and KCNQ1.

Together, the KCNE1 and KCNQ1 proteins control the electrical potential of a cardiac cell by managing the flow of positively charged potassium ions across the cell’s membrane. “We know that the protein produced by KCNE1 binds to the protein produced by KCNQ1 to regulate the flow of potassium, but we don’t know how it binds or where it binds,” says Lorigan. “We know that mutations cause differences in this binding, but we don’t know why.”

In an effort to answer these questions, Lorigan and his colleagues – including a post-doctoral fellow, five graduate students, and seven undergraduate students – are using nuclear magnetic resonance (NMR) and an advanced electron paramagnetic resonance (EPR) technique known as double electron-electron resonance (DEER) to analyze how the KCNE1 and KCNQ1 proteins are built, how they move around, and how they bind.

In DEER, special molecules are used to tag specific regions within a protein or other macromolecule. Lorigan and his team use these so-called spin labels to measure distances within the KCNE1 and KCNQ1 proteins. “That’s how we’re actually able to visualize their structure,” he says.

One year into a project funded with $1.1 million from the National Institutes of Health (NIH), Lorigan’s team has managed to define the structure of the KNCE1 protein in the cell membrane. “That was our goal for the first year,” he says. “We just submitted the paper on that.”

The ultimate goal of the four-year project, according to Lorigan, is to “get structural information and relate that to function.”  Once that fundamental work is complete, the Lorigan team will have paved the way for translational scientists to begin developing new treatments for patients with LQTS and, potentially, other forms of arrhythmia as well.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University

Illustration by Pleiotrope (own work) [Public domain], via Wikimedia Commons. Photo courtesy of Gary Lorigan.