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.

Rick Page working with senior Matt Morris, a 2018 Beckman Scholar

In a first at Miami, two biochemists awarded MIRA grants

Gary Lorigan and Dan Drew work with an EPR spectrometer.
Gary Lorigan, left, with doctoral student Dan Drew.

A new type of grant from the National Institutes of Health (NIH) is designed to allow proven and promising researchers to be more ambitious and creative in their research.

The NIH has recognized Miami University biochemists Gary Lorigan and Rick Page: They were each awarded about $1.8 million over five years, as part of the Maximizing Investigator’s Research Award, or MIRA.

The MIRA grants, part of the National Institute of General Medical Sciences (NIGMS), are highly competitive and essentially set the researcher for a career in NIH funding, said Mike Crowder, chair and professor of chemistry and biochemistry.

“It would be rare for a school like Miami to have two MIRAs; it is very unlikely for one department to have two,” he said.

After the first five years of funding, the MIRA program is set up to provide another funding cycle to the researchers, as long as the group was productive, Crowder said. The current system requires researchers to apply repeatedly for a grant.

“Given their success rate on NIH grant proposals using the ‘old’ system, Gary and Rick are positioned for consistent funding for many years. I could not be happier for them or for their students,” Crowder said.

Describing the new grant program, now in its second year, NIGMS director Jon Lorsch said, “We hope that by creating the stability for investigators, we can really empower them to be more ambitious and more creative in their research. We also hope to increase the flexibility for investigators to follow new ideas and new research directions as they arise during the course of their work. If they discover something very interesting, they’ll be able to follow that.”

Freedom to let the science guide the research

Lorigan, professor, and Page, assistant professor of chemistry and biochemistry, will each receive around $360,000 per year for five years. Page received the MIRA for Early Stage Investigators (MIRA ESI).

The funding supports their research programs, rather than individual projects.

Portrait of Gary Lorigan
Gary Lorigan

Lorigan’s research program: Membrane protein structure; heart disease

The MIRA grant gives his research group a lot of flexibility and the ability to explore new scientific directions, Lorigan said.

His research program focuses on membrane protein channels that are directly related to heart disease.

Internationally recognized as a leader in the field of membrane protein structure, he and his research group have pioneered strategies to characterize membrane proteins by using magnetic resonance techniques, such as electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) spectroscopies.

His expertise has attracted several significant collaborators with important biological problems.

His goal:

  • To develop transformative biophysical techniques to study the structural and dynamic properties of membrane proteins.
  • These state-of-the-art pulsed EPR spectroscopic techniques will move the field forward by dramatically increasing sensitivity and accuracy of distance measurements for all membrane protein systems.

Lorigan is currently adviser to a postdoctoral researcher and four graduate students and is mentor to nine undergraduate researchers.

Portrait of Rick Page
Rick Page

Page’s research program: Protein quality control; antibiotic resistance

The award “provides my laboratory with the freedom to let the science guide us,” Page said. It will advance both the protein quality control and the antibiotic resistance projects in his lab.

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.

Defects in protein quality control pathways can contribute to diseases including neurodegenerative disorders and cancers.

His goal:

  • To enhance our fundamental knowledge of protein quality control pathways and identify avenues that may be exploited for future therapeutic targeting.

He has multiple research collaborations with colleagues in chemistry and biochemistry and in bioengineering on his research project on clinical inhibitors of metallo-beta-lactamases (MBLs), which render bacteria resistant to antibiotics.

Page is currently adviser to six graduate students and mentor to 12 undergraduate researchers.

Proven and Promising
Lorigan (2003) and Page (2016) have each been named a Miami University Junior Faculty Scholar. Lorigan was named a Distinguished Faculty Scholar in 2014.

They each received a National Science Foundation CAREER grant – one of the organization’s most prestigious awards in support of junior faulty. Lorigan was the first scientist at Miami to receive one, in 2003. Page is the eighth to receive one, in 2016. (Dominik Konkolewicz, asssitant professor of chemistry and biochemistry, recently received the ninth NSF CAREER grant at Miami).

Last month Lorigan received a $450,000 grant from the National Science Foundation for his research on membrane proteins.

Research at Miami is competitive at the highest level

“We are incredibly proud to have received a MIRA ESI,” Page said. “That there are now two MIRAs in the department is continued evidence that research at Miami is competitive at the highest levels,” he said.

There are 231 established MIRA grantees and 192 ESI MIRA grantees nationally, awarded over the first two years of the program, according to the NIGMS.


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.

Photos by Scott Kissell and 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 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.