College of Graduate Studies

UT scientists, students help U.S. Geological Survey develop model to predict algal bloom toxins

By Christine Long : July 29th, 2016

Water quality researchers and students at The University of Toledo Lake Erie Center who make daily E. coli forecasts for the public beach at Maumee Bay State Park are helping the U.S. Geological Survey (USGS) develop a model to estimate the level of harmful algal blooms in Ohio waters.

Sampling is underway for the USGS-led project at seven water treatment plant intakes and four recreational sites throughout the state, including the public beach at Maumee Bay State Park.

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Kevin Corbin, UT senior, left, Ryan Jackwood, UT PhD student, and Jessica Reker, a senior at Xavier University, collected water samples at Maumee Bay State Park.

A USGS scientist joined the UT team to collect samples and other data earlier this month.

“We are helping the USGS build a database in order to be able to make real-time predictions for toxins, like microcystin, in Lake Erie and inland lakes in northeast and southwest Ohio using environmental factors such as turbidity, pH, phycocyanin and water level change, instead of waiting for test results,” Pam Struffolino, UT Lake Erie Center research operations manager, said. “The goal is to use the standard toxin-measuring methods to verify the model — similar to how we developed our swimming safety nowcasts for bacteria levels.”

“Site-specific models are needed to estimate the serious public health concern from toxin concentrations at a water intake or beach,” said Donna Francy, a USGS hydrologist and water-quality specialist. “Models help estimate toxin concentrations so that swimmers and boaters can be warned and water treatment plants can take measures to avoid or appropriately treat the raw water.”

Scientists are scheduled to collect data at the sites several times a week through algal bloom season this year. This marks the third year of collecting samples for the project.

For more information about the project, click here.

 


Chemical that disrupts cell division could help to treat cancer – By Shengnan Du | Special to The Blade

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Shengnan Du is a PhD student stuyding biochemistry and cancer at the University of Toledo.

Typical treatments for cancer include surgical removal of the tumor followed by chemotherapy and/or radiation therapy. The specific treatment depends on the type of cancer and how advanced it is at the time of diagnosis.

Unfortunately, many cancer cells are smart enough to survive initial treatment. Why does this happen? One reason is that cancer grows into a mixed population of cells with different ways of resisting treatment. Normal cells are required to produce identical daughter cells. But cancer cells divide and grow rapidly, therefore they do not always produce identical daughter cells. The original cancer cell then eventually grows into a mixture of cancer cell subpopulations within the same tumor.

Treatments aimed at a specific target often kill only a specific subpopulation of cancer cells within that tumor. The other subpopulations that escape the treatment will continue to divide and grow, which is how the tumor regrows and resists further treatment.

Chemotherapy in clinical trials is designed to kill cells by aiming at specific targets, such as damaging DNA; causing leakage of cancer cell membranes; inhibiting new protein synthesis; interfering with essential cell functions, or blocking cells from dividing and growing.

It is imperative to develop new drugs that will kill all cancer subpopulations by aiming at multiple targets, affecting the entire cancer cell population. That is what we are studying at the University of Toledo.

As a doctoral student in William Maltese’s laboratory in the UT College of Medicine and Life Sciences, formerly the Medical College of Ohio, my research is focused on developing a new drug for treatment of cancer that can inflict damage on many different targets within the cell. In collaboration with medicinal chemists Christopher Trabbic and Paul Erhardt, we have designed small molecules that kill cancer cells by unique mechanisms. One chemical that we have developed is called 6-MOMIPP, which targets microtubules within dividing cancer cells.

Microtubules are extremely important for cells to maintain many normal functions. The microtubules inside your cells give the cell both shape and function, similar to how bones support the muscles and movement of your body. Microtubules join together to make polymers, which form a road that transports materials and nutrients to
different locations within the cell or to be exported out of the cell. And most importantly, during cell division microtubules perfectly separate your duplicated chromosomal DNA so that each daughter cell will equally inherit the same genetic information. Therefore, disrupting microtubules will target several essential functions that will kill growing cancer cells.

We believe that one of the most important effects of 6-MOMIPP on cancer is the disruption of microtubules, which stops the separation of duplicated DNA. Importantly, we have found that 6-MOMIPP is less toxic to normal human cells than it is to cancer cells. This indicates that 6-MOMIPP should selectively kill only the rapidly growing cancer cells.

A unique property of 6-MOMIPP is that it can cross the blood-brain barrier, which functions like a wall between your brain and blood vessels to prevent many things in your blood from getting into your brain. Many chemotherapy drugs cannot be used for treating brain tumors because they can not cross this protective barrier. Since 6-MOMIPP can cross the blood-brain barrier, it has potential for treating tumors in the brain.

We have tested the effects of 6-MOMIPP on multiple melanoma and glioblastoma human cancer cell lines growing in laboratory culture dishes and the chemical is very potent in killing these rapidly growing cancers under these circumstances. To better predict the possible benefits for treating cancer patients, our future studies will evaluate 6-MOMIPP in a brain tumor model to determine if the drug can effectively shrink the tumor size.

If our continued studies are successful, the results could pave the way for clinical trials of 6-MOMIPP, alone or as a combinationwith other drugs, to increase the effectiveness of current cancer treatments.

Shengnan Du is a PhD student in the department of biochemistry and cancer biology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Shengnan is doing her research in the laboratory of Dr. William Maltese. For more information, contact Shengnan.Du@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.


UT Researchers Partner with Green Ribbon Initiative to identify Invasive Plant Species

Three University of Toledo researchers have teamed up with the Green Ribbon Initiative to develop a strategy for partner organizations to prioritize and manage invasive plant species common in the Oak Openings Region.

Dr. Jonathan Bossenbroek, professor of ecology, Dr. Todd Crail, UT lecturer in the Department of Environmental Sciences, and Sara Guiher, a graduate student, are working with the initiative, designed to preserve the natural landscape in the region, to compile a list of what are known as terrestrial invasive plant species. Invasive plant species can be non-native to a region, though only a small percentage of non-native plants qualify as invasive.

UT graduate student Sara Guiher pointed out a black oak at the Kitty Todd Nature Preserve in Swanton. Black oak is one of the native species that the Green Ribbon Initiative is trying to protect.

UT graduate student Sara Guiher pointed out a black oak at the Kitty Todd Nature Preserve in Swanton. Black oak is one of the native species that the Green Ribbon Initiative is trying to protect.

“Plants that are able to exclude native plants, take habitats away from native animals, those are the ones we are really trying to address,” Guiher said.The project began in May 2015 with the identification phase, during which Guiher and Bossenbroek devised an assessment for partner organizations to determine where their priorities for invasive species management should be focused. After figuring which invasive plants each partner organization is dealing with, the goal is to develop best management practices for the conservation of the area. The development of the Oak Openings Region invasive species strategy brings together organizations such as the Nature Conservancy, Metroparks of the Toledo Area, the Olander Parks System, and the Ohio Department of Natural Resources, among many others, to make informed decisions about how to control invasive species.

“A big part of this is communication between partners,” Guiher said. “There are all those different agencies, and they each have their own approach; we’re basically trying to bring all of them together and communicate about the spread of invasive plants and decide on consistent strategies to manage them.”

“All these organizations have their own properties and their own, sometimes different management goals — the metroparks have a different mission than the Nature Conservancy, different from the Department of Natural Resources — trying to find a framework for dealing with terrestrial invasive species is what we’ve been asked to do,” Bossenbroek said.

Bossenbroek said his experience includes similar projects geared toward aquatic invasive species, such as the zebra mussel. His work has always included examination into spread of invasive species into the environment they might take over, which translates to this project on terrestrial invasive species as well.

“You use the same tools, the same types of analyses, to predict where things are going to live and how they get around,” Bossenbroek said. “There are usually two ways they move around: They get moved around naturally — birds, wind, streams — or by people. A lot of invasive species are easily transmitted by people.”

The next phase of the partnership will include digital modeling situations, in which variables such as topography and vegetation can be manipulated to figure out ideal habitats for invasive plant species. This type of model was what Bossenbroek said he used when examining aquatic invasive species.

“The next step is the modeling using software; taking those variables and possible vectors and trying to determine where the plant species may establish in the region, which will streamline the process,” Guiher said. “We can’t necessarily cover all the partners’ land, but we can try to give them guidance as to where those plants might show up.”

To learn more about the Green Ribbon Initiative, visit the Oak Openings Region’s website at oakopenings.org/about.


Upcoming MBA and Executive MBA Exploration Events

Click here for the pdf version

Join us at an upcoming MBA or Executive MBA Exploration Event!

Discover how an MBA or Executive MBA from The University of Toledo can impact your future!

We would like to invite you to The University of Toledo, to attend an Exploration Event to learn more about the Professional and Executive MBA programs available through the UT College of Business and Innovation.

While some MBA students do have a business background, many students and working professionals have degrees in areas such as Engineering, Pharmacy, the Arts and more. An MBA is proven to be a valuable addition to successful careers in many fields, as well as to the expanding number of people starting and operating their own businesses.

Professional MBA Program (MBA)

Most of our MBA students are employed full-time in the Toledo area, which is why the majority of our Professional MBA classes are scheduled during the evenings. The Professional MBA program is the only MBA program in Northwest Ohio to offer a flexible completion plan, as well as nine areas of concentration. The Professional MBA program gives students/professionals exposure to all areas of the business enterprise while providing an opportunity to focus on a specific area of interest.

Executive MBA Program (EMBA)

The Executive MBA program at the University of Toledo is one of the most affordable AACSB- accredited EMBA programs in the United States that can be completed in just 12 months. The EMBA program is designed specifically for individuals who have several years of progressive or managerial experience, and is delivered in a flexible hybrid format of in-person and tech- enhanced instruction, with only one on-campus weekend per month.

The upcoming Exploration Event dates are:

MBA Exploration Event
Wednesday, July 27, 5:30 p.m. to 7:45 p.m.
Savage & Associates Business Complex, Room 4100. This event is for any interested prospective MBA student. Free pizza will be provided.
Reserve your seat today by calling 419.530.5680 or emailing COBIGradPrograms@utoledo.edu.

Space is limited!

Executive MBA Exploration Event
Saturday, August 13, 10:30 a.m. to 1:00 p.m.
Call or email now to register for our Executive MBA Exploration Event. 419.530.5680 or email emba@utoledo.edu

You can also learn more, and see testimonials from former students, at utoledo.edu/business/graduate/emba/prospectivestudents

 


Graduate Student to discuss Invasive Plants July 13 at Lake Erie Center

UT graduate student Sara Guiher will deliver a talk titled “Neighborhood Watch: Learn to Identify and Manage Invasive Plants in Your Yard” Wednesday, July 13, at 7 p.m. at the Lake Erie Center, 6200 Bayshore Road, Oregon.

The free event is part of the UT Lake Erie Center’s Naturalist Series, which welcomes a variety of speakers from different areas of expertise to share their insights.

invasive plant flyerGuiher’s talk connects to a larger project she began last year with Dr. Jonathan Bossenbroek, UT professor of ecology, and Dr. Todd Crail, UT lecturer in the Department of Environmental Sciences. In partnership with the Green Ribbon Initiative, the three worked to compile a list of invasive plant species prevalent in the Oak Openings Region.

Invasive plants can exist anywhere. Even home gardens can act as habitats for invasive species, and Guiher hopes to inform attendees of the various types of invasive species to look for in their yards.

Garlic mustard, honeysuckle, and landscaping plants such as Callery pear and Japanese barberry are among the species that can be prevalent and possibly invasive in home gardens. Guiher said she will not only highlight which plants to look out for, but also offer some native alternatives for those plants and how homeowners can move forward in their gardens.

“My goal is to introduce local residents to invasive plants that are common in the area and likely already present on their properties, along with some effective management strategies. Controlling invasives in our yards can have a positive impact in our neighborhoods, as well as on native plant and animal communities,” Guiher said.

“I’m excited to provide examples of native plants that can be used in home landscapes,” she added. “Following the talk, we plan to take a short walk to get some experience identifying invasive plants in the field.”

To learn more about the Lake Erie Center and its events, click here.


Understanding how the nervous system works – By Eric Starr | Special to The Blade

Have you ever thought about how you recall information from something you learned in the past? Or why stressful situations can affect your mood or behavior?

These changes do not just happen. They occur in part because of communication signals that alter activity in your nervous system.

Your nervous system is a complex network of nerve cells called neurons that comprise your brain, spinal cord, and peripheral nervous system. Your brain contains more than 100 billion neurons that are constantly communicating with one another by releasing chemical messengers called neurotransmitters.

This communication occurs at a region between two neurons called a synapse. The neurotransmitters are released from communicating neurons through synaptic terminals where they move across to the other end of the synapse and interact with receptors on the neuron receiving the message. When these receptors receive these neurotransmitters, they cause the neuron to increase or decrease its activity.

It is through this process that the nervous system is able to coordinate your movement, your thoughts, and your actions. For example, as you are reading the words of this article, neurons near your eyes are releasing neurotransmitters to neuronal circuits that control visual and language centers in your brain, which decode the words you are reading into a context that you can understand.

Eric-Starr

Eric Starr is a PhD student in the department of neurosciences at the University of Toledo college of medicine and life sciences.

Researchers have discovered that the activity of neurons can be strengthened or weakened by adjusting the size of the neuron’s synaptic terminal or the amount of neurotransmitters released from it. Additionally, neurons can adjust their response to neurotransmitters by altering the amount of their receptors. This ability of neurons to alter their synaptic strength is called synaptic plasticity, which is important to understand because it has been implicated in learning, pain, and stress.

Research conducted in the department of Neurosciences in the University of Toledo College of Medicine and Life Sciences, seeks to understand the mechanisms by which synaptic plasticity occurs in the nervous system.

Our lab has demonstrated that a signaling molecule named pituitary adenylate cyclase-activating polypeptide, or PACAP, can induce synaptic plasticity. PACAP regulates social, motor, and stress behaviors and has been implicated in psychological disorders such as post-traumatic stress disorder. By understanding how PACAP causes synaptic plasticity, we can find clues as to how disruptions in its signaling can lead to the development of such disorders.

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One focus of our lab has been to better understand how PACAP induces synaptic plasticity in neurons. Using techniques to measure synaptic activity, we have learned that PACAP can immediately cause synaptic plasticity in a subset of neurons in the peripheral nervous system by robustly increasing their activity. PACAP causes this short-term synaptic plasticity by increasing the amount of neurotransmitters that these neurons release from their synaptic terminals.

In addition to this short-term plasticity, we have discovered that when we wait 48 hours following PACAP treatment, neuronal activity is even higher.

Coined as long-term PACAP-induced plasticity, we have demonstrated that this synaptic plasticity also is associated with an increase in the amount of neurotransmitters released from synaptic terminals. However, unlike in the short-term, this long-term PACAP-induced synaptic plasticity also is associated with an increase in the size of synaptic terminals and an increase in the amount of receptors that neurotransmitters can bind to.

In addition, we have recently discovered that the long-term PACAP-induced synaptic plasticity is mediated by mechanisms that are distinct from the short-term effects. For example, unlike the short-term effects, the long-term requires the synthesis of new proteins that we plan to investigate further.

We are currently researching how PACAP can sustainably alter neuronal communication. Studies are under way investigating the contribution of individual proteins that PACAP can potentially recruit to cause this long-term synaptic plasticity.

These discoveries are exciting because they reveal novel ways your nervous system works to cause synaptic plasticity. By understanding synaptic plasticity, we can better understand the role of synaptic communication in the context of human behavior and disease.

Eric Starr is a PhD student in the department of neurosciences in the University of Toledo college of medicine and life sciences biomedical science program, formerly the Medical College of Ohio. Mr. Starr is doing his research in the laboratory of Dr. Joseph Margiotta. For more information, contact Eric.Starr@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.


UT Nursing Student Wins National Association’s Core Values Award

Advocacy, professionalism, quality education, leadership and autonomy are the core values of the National Student Nurses’ Association, which recently presented Amanda Nuckols its Core Values Award.

The Core Values Award is given nationally to one student per year. The award is designed to inspire students to embody the values most important to members of the National Student Nurses’ Association.

Amanda Nuckols received the Core Values Award from the National Student Nurses’ Association.

Amanda Nuckols received the Core Values Award from the National Student Nurses’ Association.

To be eligible for the Core Values Award, students must be pursuing a nursing degree and be a member of the National Student Nurses’ Association, and they must be nominated by faculty.

“It’s an honor working with a student that demonstrates these core values. She’s amazing. She’s humble. I’ve never met another student like her in all my years as an advisor,” said Karen Tormoehlen, Student Nurses Association advisor and assistant professor, who nominated Nuckols for the award.

Nuckols graduated in May from the Clinical Nurse Leader Program, which allows students with a bachelor’s degree in another discipline to receive a master’s degree in nursing in two years.

In her time as a nursing student, Nuckols served as president, cohort representative and convention planner of the UT Student Nurses’ Association. She also served on the Nominations and Elections Committee of the national organization.

In addition to these roles, Nuckols helped build a playground for the local Ronald McDonald House, assisted in a community event that gave families impacted by human trafficking a day at the zoo, led the local Student Nurses Association chapter in providing a bountiful Christmas for orphans, participated in medical mission trips to developing countries, volunteered at a free clinic serving the homeless, and more.

Nuckols will return to the University this fall to continue her studies with the Family Nurse Practitioner Program. She also intends to work as a registered nurse while pursuing her third degree.

“This is a huge honor,” Nuckols said. “I have worked hard to do well as I was completing my studies, while also being involved in a variety of organizations and roles. I am so glad that my effort and dedication have paid off.”


New Dean Selected to Lead College of Graduate Studies

By Jon Strunk : May 31st, 2016

Graduate students accounted for nearly 40 percent of all University of Toledo graduates during the spring 2016 commencement exercises, and UT officials have identified the leader who will continue to elevate the institution’s graduate programs.

Dr. Amanda Bryant-Friedrich will serve as dean of the College of Graduate Studies beginning July 1, pending approval by the UT Board of Trustees, following the retirement of Dr. Patsy Komuniecki.

Bryant-Friedrich

Bryant-Friedrich

“Graduate education is a key area that The University of Toledo distinguishes itself from our peers,” said John Barrett, interim provost and executive vice president for academic affairs. “The breadth of our programs, our facilities and equipment, and our commitment to engaging students in research all create experiences that set UT apart for those seeking an advanced degree.”Barrett’s sentiment was echoed by Bryant-Friedrich, who plans to focus on increasing UT’s graduate student enrollment and its undergraduate to graduate student retention. She said she would look to increase the number of pipeline programs, which enable students to earn undergraduate and graduate degrees at UT more rapidly. Growing philanthropic support for the college also will be a priority.

“Throughout my career, it has been working with graduate students that gives me the most joy,” Bryant-Friedrich said. “I love watching them progress in their studies, become professionals, and continue to carry the UT flag during the course of their careers.”

Calling UT’s graduate programs jewels, she said she plans to work with faculty, alumni, and Marketing and Communications to better spread the word about the University. She also spoke about the need to ensure programs are reinventing themselves to meet the needs of the changing world.

“I know from experience that personal interaction has a big impact when it comes to graduate student recruitment,” she said.

UT President Sharon L. Gaber praised Bryant-Friedrich’s work on behalf of graduate education as part of the Strategic Enrollment Planning process.

“Dr. Bryant-Friedrich has the energy and enthusiasm to build the strength of our graduate programs and ensure students know of the endless possibilities available to them with a UT education,” Gaber said.

Bryant-Friedrich, an associate professor in the Department of Medicinal and Biological Chemistry in the College of Pharmacy and Pharmaceutical Sciences, added that incoming Provost Andrew Hsu has encouraged her to attain full professorship in the coming years, which aligns well with her goals and plans.

“I am looking forward to working with Dr. Bryant-Friedrich to strengthen and promote the outstanding graduate programs at The University of Toledo,” Hsu said.


UT student discovers first grass carp eggs in Great Lakes tributary

June 2, 2016

UT student discovers first grass carp eggs in Great Lakes tributary

A graduate student at The University of Toledo is the first researcher to find direct proof of grass carp, a type of invasive Asian carp, spawning in a Great Lakes tributary.

Holly Embke collected eight grass carp eggs last summer in the Sandusky River, which flows into Lake Erie. She discovered the eggs between Fremont, Ohio, and Lake Erie’s Sandusky Bay after a period of heavy rains.

The fish eggs, which were confirmed through DNA testing, mark the first direct evidence of the invasive species reproducing in the Great Lakes basin. Embke’s paper is published in the Journal of Great Lakes Research. Embke also will present her work at the annual conference of the International Association for Great Lakes Research on Thursday, June 9 at the University of Guelph in Ontario, Canada.

This research was conducted as a follow-up to U.S. Geological Survey findings in 2013 that indicated four young grass carp taken from the Sandusky River were the result of natural reproduction.

“Lake Erie commercial fishermen have reported catching grass carp since the mid-1980s, but those catches were thought to be sterile escapees from ponds and small lakes that were legally stocked for aquatic weed control,” said Embke, who is pursuing a master’s degree in biology in the Department of Environmental Sciences. “The discovery of these eggs in the Sandusky River means that this invasive species of Asian carp, which consumes large amounts of freshwater vegetation, is naturally reproducing in our Lake Erie watershed.”

Although considered a species of Asian carp, wild adult grass carp pose significantly different risks to the Lake Erie ecosystem than bighead carp and silver carp, which are the two invasive Asian carp species of great concern in the Mississippi River basin. Both bighead carp and silver carp consume plankton, and if these species were to make their way into the Great Lakes basin they would compete for the same source of food that ecologically and economically important native fish species need to survive. Silver carp are well-known for their jumping ability.

Grass carp pose a risk to waterfowl habitat and wetlands, but they do not eat plankton and are unlikely to compete directly with native fish. Grass carp do not jump and are primarily herbivorous. They can alter habitats for native fish communities near the shoreline by eating submerged, rooted plants and weeds.

Scientists with UT, the Ohio Department of Natural Resources (ODNR) Division of Wildlife and the USGS are collecting additional samples from the Sandusky River to continue studying the habitat requirements of grass carp spawning in order to inform methods for control of all invasive species of Asian carp.

“While the discovery of eggs is disconcerting, grass carp continue to remain present in the Lake Erie system in very low abundance,” said Rich Carter, executive administrator for fish management and research with the Ohio DNR Division of Wildlife. “There is currently no evidence of negative impacts to the Lake Erie ecosystem that can be attributed to grass carp. However, it is important that we remain vigilant and continue to build understanding about this species in Lake Erie and throughout the Great Lakes.”

“Given the similarities in reproductive strategies, this ongoing research on grass carp spawning may help us minimize the risk of bighead carp and silver carp from establishing a foothold in the Great Lakes,” said Patrick Kocovsky, a USGS research fishery biologist. “What we learn here also might apply to potential control strategies in tributaries to the Mississippi River.”

Sterile grass carp can be legally stocked in Ohio, as well as Indiana, Illinois, New York and Pennsylvania. They are a popular pond and small lake management tool because they control aquatic weeds. Ohio has banned the stocking of fertile grass carp and Michigan has banned all grass carp. The fish was first imported to the U.S. from Taiwan and Malaysia in 1963.

Researchers will next work to identify the spawning and egg hatching locations for the Sandusky River.

“Predicting locations and conditions where grass carp spawning is most probable may aid targeted efforts at control,” Embke said.

Embke is based out of UT’s Lake Erie Center where she does all of her sample processing and analysis.

The UT Lake Erie Center is a research and educational facility focused on environmental conditions and aquatic resources in Maumee Bay and western Lake Erie as a model for the Great Lakes and aquatic ecosystems worldwide.

“This discovery was student research,” Christine Mayer, UT ecology professor, said. “Our graduate students are doing work that is useful. They’re not just in the lab. They’re out in our region’s rivers and lakes providing information that helps solve problems.”

For more information on Asian carp or how to report sightings, go to wildlife.ohiodnr.gov.

Media contacts:
Christine Long
The University of Toledo
christine.long2@utoledo.edu
419.530.2077

Marisa Lubeck
U.S. Geological Survey
mlubeck@usgs.gov
303.526.6694


How the white-footed mouse can help humans fight diseases – by Adaeze Izuogu

Clues sought for treatment of flaviviruses by studying cells

In recent years, the world has been threatened with dangerous disease-causing viruses such as Ebola, Dengue, SARS, and currently, Zika virus. These viruses all infect animals before transmission to humans. Curiously, most infected animals do not get sick despite infection. It is a puzzle to researchers that these animals resist the viral diseases and suggests that the animals have some survival secrets that we humans do not.

A group of viruses called flaviviruses presents an even more complex picture of human virus infection and disease. These include many widespread viruses such as West Nile, Zika, Powassan, and tick-borne encephalitis virus. An insect vector is required to transmit these viruses from animals to humans, which most often occurs by the bite of a mosquito or tick that had previously bitten an infected animal.

The human disease that develops from the infected insect could involve a simple fever or a very severe multi-organ illness or even brain damage with possible long-term consequences. Unfortunately, there is currently no specific treatment for infection with this group of viruses, and up to 60 percent of people who develop disease can die from infection.

Our studies, conducted in the laboratory of Dr. Travis Taylor at the University of Toledo College of Medicine and Life Sciences, are seeking clues for treatment of flaviviruses by studying cells of a natural animal host: the white-footed mouse (Peromyscus leucopus). This is the most common wild rodent in North America.

Ticks infected with flavivirus that bite a white-footed mouse can pass the flavivirus to that mouse. The mouse remains infected for a long time but without disease symptoms. Any other tick that then bites this mouse for a blood meal can acquire the flavivirus infection and transmit it to a human.

The main goal of our research is to identify how the white-footed mouse remains free of disease while infected with the flavivirus, unlike humans. If we can find the exact process of defense against disease in the white-footed mouse, we may be able to use a similar approach to combat flavivirus disease in humans.

We discovered that the flavivirus grows to much lower numbers in cells in culture from the white-footed mouse as compared to cells from the house mouse (Mus musculus), which is not resistant to flavivirus disease symptoms.

We have now tested several strains of tick-borne flaviviruses. Every strain tested exhibits the same low numbers in cells of the white-footed mouse. Further research revealed that flavivirus growth in the white-footed mouse is blocked when the virus attempts to make more copies of itself within the cell, which is why there are fewer virus particles in the cell culture as compared to the house mouse.

So why is the same flavivirus more dangerous in some species than others? We believe this difference is because the white-footed mouse’s higher immune system activity defends against virus particles. Generally, the higher the activity of your immune system, the better your defense against disease will be.

The next step was to identify the main biochemical pathway involved in defense. We used molecular tools to block the interferon response, which is the body’s process of sensing viral infection and activating an immune defense. We discovered that when this pathway is blocked in cells of the white-footed mouse, there are many more virus particles in these cells. This suggests that the white-footed mouse cell defense activity suppresses virus growth.

We’ve learned that virus detection and interferon activation prevent the growth of flaviviruses in the white-footed mouse. The next step is to identify specific proteins in this mouse that are triggered by the interferon pathway to inhibit flavivirus disease after infection. We anticipate that these specific proteins will help in drug design by mimicking the survival strategy of the white-footed mouse.

Adaeze Izuogu is a PhD student in the Department of Medical Microbiology and Immunology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Adaeze is doing her research in the laboratory of Dr. Travis Taylor. For more information, contactAdaeze.Izuogu@rockets.utoledo.edu