Medicine can treat infections after people get sick, but 性视界传媒 infectious disease expert Mollie Jewett is seeking to halt Borrelia burgdorferi bacteria, which causes Lyme disease, in its tracks without relying on general antibiotics. Her goal: 鈥渟tarve鈥� the bacteria of the nutrients they need to function before they spread through the human body.

Jewett, professor and head of the Immunity and Pathogenesis Research Division at 性视界传媒鈥檚 College of Medicine, is supported by a recently renewed five-year, $2.5 million grant from the National Institutes of Health.

She is entering a third consecutive federally funded research cycle with $513,314 received this year. Jewett鈥檚 research builds upon more than a decade of discoveries that have narrowed the search for ways to stop B. burgdorferi from triggering Lyme disease, one of the nation鈥檚 most common vector-borne diseases. Her team includes a 性视界传媒 undergraduate who occasionally struggled to walk because of pain from Lyme disease.

The disease is spread by blacklegged ticks that become infected after biting mammals or birds carrying the bacteria. The ticks are so small, humans often don鈥檛 notice they have been bitten. Symptoms include fever, chills, headache and fatigue, which often are misdiagnosed as a virus or the flu. Even after treatment, Lyme disease patients can face complications including nervous system and heart issues, severe fatigue and arthritic pain.

The disease is most commonly found in Maine to Virginia and in the upper Midwest but is spreading as suburban growth enters wildlife areas. 性视界传媒 reports few cases of Lyme disease annually, but travelers who go to endemic areas like New England are at increased risk.

A New Approach to Battle Borrelia

性视界传媒 researchers are focused on how B. burgdorferi manages to survive and thrive as it spreads in ticks and mammals to humans.

鈥淭he bacteria need to adapt to two different environments, and so we want to know how it does that,鈥� Jewett says. 鈥淲e鈥檙e looking at what the bacteria eat and what it needs to survive. In our lab, we call Borrelia a wimpy pathogen because it can鈥檛 make a lot of the nutrients it needs on its own, and so it scavenges what it needs from wherever it is.鈥�

The first iteration of the NIH grant allowed the scientists to screen all of the bacteria鈥檚 genes that might be important for the infection. With the second grant, Jewett targeted three genes that appeared to play a role in spreading the infection from a bite on the skin to other parts of the human body.

“One of these three genes we found is important to the ability of the bacteria to consume riboflavin. We want to target this gene and see if we can starve the bacteria.” 鈥� Mollie Jewett, 性视界传媒 infectious disease expert

Now they have focused on riboflavin, commonly known as vitamin B2, after discovering that B. burgdorferi salvages the vitamin from each host to sustain itself.

鈥淥ne of these three genes we found is important to the ability of the bacteria to consume riboflavin,鈥� Jewett says. 鈥淲e know that riboflavin is a precursor for other cellular activities that are important to the metabolism of the bacteria. Essentially, we want to target this gene and see if we can starve the bacteria.鈥�

If their theory is successful, it could lead to therapies specific to B. burgdorferi that would prevent successful bacterial infection by limiting its riboflavin uptake. An advantage of such potential treatments would be that patients don鈥檛 have to take general antibiotics that can also harm the body鈥檚 good bacteria and increase risks for antibiotic-resistant bacteria.

The 性视界传媒 team is collaborating with Baylor University scientists to trace exactly how riboflavin is used by the bacteria.

Students Driving Discovery

Biomedical sciences doctoral student Anna Schulz 鈥�25MS played a key role in pinpointing specific ways the bacteria use riboflavin to generate energy. She served as first author on a recent publication examining these processes, and says she鈥檚 looking forward to growing as a researcher in this next phase.

鈥淎s a first author, I took more ownership over the experiments and the writing process,鈥� Schulz says. 鈥淸Jewett] was really great about letting me lead the project as a student. Borrelia is so unique, and there鈥檚 still so much we don鈥檛 know, and that鈥檚 what keeps me engaged with this research.鈥�

“… I couldn鈥檛 treat it until years after I got infected. So, I truly care about finding new treatments for Lyme disease.” 鈥� Grace Easterling, 性视界传媒 biomedical sciences student

Third-year biomedical sciences undergraduate Grace Easterling says she was drawn to Jewett鈥檚 lab because she previously developed Lyme disease and suffered tremendous joint pain. She was determined to find a way to protect others.

鈥淚t was something that, because we live in 性视界传媒, wasn鈥檛 caught early because it鈥檚 not as common,鈥� Easterling says. 鈥淚 struggled for a long time to get diagnosed, and I couldn鈥檛 treat it until years after I got infected. So, I truly care about finding new treatments for Lyme disease and understanding the bacteria.鈥�

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI099094. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

A multidisciplinary team led by College of Medicine biomedical researcher Bradley Jay Willenberg with Mollie Jewett (性视界传媒 Burnett School of Biomedical Sciences) and Andrew Dickerson (University of Tennessee) lined 3D capillary gel biomaterials with human cells to create engineered tissue and then infused it with blood. Testing showed mosquitoes readily bite and blood feed on the constructs. Scientists hope to use this new platform to study how pathogens that mosquitoes carry impact and infect human cells and tissues. Presently, researchers rely largely upon animal models and cells cultured on flat dishes for such investigations.

Further, the new system holds great promise for blood feeding mosquito species that have proven difficult to rear and maintain as colonies in the laboratory, an important practical application. The Willenberg team鈥檚 work was published Friday in the journal .

Mosquitos have often been called the world鈥檚 deadliest animal, as vector-borne illnesses, including those from mosquitos cause more than 700,000 deaths worldwide each year. Malaria, dengue, Zika virus and West Nile virus are all transmitted by mosquitos. Even for those who survive these illnesses, many are left suffering from organ failure, seizures and serious neurological impacts.

鈥淢any people get sick with mosquito-borne illnesses every year, including in the United States. The toll of such diseases can be especially devastating for many countries around the world,鈥� Willenberg says.

This worldwide impact of mosquito-borne disease is what drives Willenberg, whose lab employs a unique blend of biomedical engineering, biomaterials, tissue engineering, nanotechnology and vector biology to develop innovative mosquito surveillance, control and research tools. He said he hopes to adapt his new platform for application to other vectors such as ticks, which spread Lyme disease.

鈥淲e have demonstrated the initial proof-of-concept with this prototype鈥� he says. 鈥淚 think there are many potential ways to use this technology.鈥�

Captured on video, Willenberg observed mosquitoes enthusiastically blood feeding from the engineered tissue, much as they would from a human host. This demonstration represents the achievement of a critical milestone for the technology: ensuring the tissue constructs were appetizing to the mosquitoes.

鈥淎s one of my mentors shared with me long ago, the goal of physicians and biomedical researchers is to help reduce human suffering,鈥� he says. 鈥淪o, if we can provide something that helps us learn about mosquitoes, intervene with diseases and, in some way, keep mosquitoes away from people, I think that is a positive.鈥�

Willenberg came up with the engineered tissue idea when he learned the National Institutes of Health (NIH) was looking for new in vitro 3D models that could help study pathogens that mosquitoes and other biting arthropods carry.

鈥淲hen I read about the NIH seeking these models, it got me thinking that maybe there is a way to get the mosquitoes to bite and blood feed [on the 3D models] directly,鈥� he says. 鈥淭hen I can bring in the mosquito to do the natural delivery and create a complete vector-host-pathogen interface model to study it all together.鈥�

As this platform is still in its early stages, Willenberg wants to incorporate addition types of cells to move the system closer to human skin. He is also developing collaborations with experts that study pathogens and work with infected vectors, and is working with mosquito control organizations to see how they can use the technology.

鈥淚 have a particular vision for this platform, and am going after it. My experience too is that other good ideas and research directions will flourish when it gets into the hands of others,鈥� he says. 鈥淎t the end of the day, the collective ideas and efforts of the various research communities propel a system like ours to its full potential. So, if we can provide them tools to enable their work, while also moving ours forward at the same time, that is really exciting.鈥�

Willenberg received his Ph.D. in biomedical engineering from the University of 性视界传媒 and continued there for his postdoctoral training and then in scientist, adjunct scientist and lecturer positions. He joined the 性视界传媒 College of Medicine in 2014, where he is currently an assistant professor of medicine.

Willenberg is also a co-founder, co-owner and manager of Saisijin Biotech, LLC and has a minor ownership stake in Sustained Release Technologies, Inc. Neither entity was involved in any way with the work presented in this story. Team members may also be listed as inventors on patent/patent applications that could result in royalty payments. This technology is available for licensing. To learn more, please visit ucf.flintbox.com/technologies/44c06966-2748-4c14-87d7-fc40cbb4f2c6.

The NIH provided the total $1.2 million grant for four years. RO1 or Research Project Grants provide support for health-related research by a sole investigator that addresses a public health need with an innovative approach. Only about 12 percent of new investigator RO1 applications are actually funded, making the grants highly competitive.

Dr. Deborah German, vice president for medical affairs and dean of the College of Medicine, applauded Dr. Jewett鈥檚 accomplishment. 鈥淩esearch is the heart of academic medicine because medical research is an invisible safety net for all of us,鈥� she said. 鈥淭his grant is an exciting and well-deserved validation of Dr. Jewett鈥檚 research and the spirit of discovery that she models.

Dr. Jewett鈥檚 research focuses on Borrelia burgdorferi, the bacteria that cause Lyme disease, and ways to diagnosis the disease earlier and better. Lyme disease is the most commonly reported vector-borne illness in the United States and is on the rise nationwide, yet definitive diagnosis of the disease remains a challenge. That means sufferers can go untreated 鈥� increasing their chances for lifelong complications, including joint inflammation, heart and brain/nervous system problems.

Lyme disease results from a bacterial infection spread through the bite of a blacklegged tick but because the ticks are so tiny, many sufferers never notice they had been bitten. Tick bites and infection can occur when people are participating in popular outdoor activities, including gardening, hunting and hiking. You also can get Lyme disease from walking in high grasses or having a pet that may carry ticks into your home.

Dr. Jewett likes to use a fishing analogy to explain her research. She has used magnetic beads to 鈥渇ish鈥� for specific antibodies that people produce after they are infected. The RO1 grant will fund new innovative efforts to 鈥渇ish鈥� for the unique genetic components of the Borrelia burgdorferi important during an infection. 聽This research is especially important because compared to other bacteria, Borrelia burgdorferi 鈥渇lies under the radar,鈥� without obvious toxic or virulent properties that make it difficult to understand how it makes people sick, Dr. Jewett said.

Dr. Jewett called the RO1 鈥渢he pinnacle of my career thus far. It鈥檚 a life changer.鈥�

The NIH grant is the latest recognition of her work by the public and the research funding community. In February, Dr. Jewett presented her research at the College of Medicine鈥檚 first Luminary Series Lecture of 2013. Days after the Luminary Series, the National Research Fund for Tick-Borne Diseases (NRFTD) announced she had received a $60,000 grant to further her research into mechanisms of Borrelia burgdorferi gene regulation, and how the bacteria functions during an infection.

The presentation: 鈥淒iagnosing Lyme in the Nick of Time鈥� showed the impact of Dr. Jewett鈥檚 research on the most commonly reported vectorborne illness in the United States. Lyme disease is on the rise nationwide yet there is currently no definitive method of testing for the disease. That means sufferers can go untreated 鈥� increasing their chances for lifelong complications.

Dr. Jewett is developing an assay that she hopes will give the most accurate diagnosis for the disease. That is where the 鈥渇ishing鈥� analogy comes in. People who are infected with tick-borne disease produce antibodies to fight the infection and Dr. Jewett鈥檚 team is working to find a better way to 鈥渇ish鈥� for proof of Borrelia Burgdorferi, the bacteria that cause Lyme disease. The 鈥渂ait鈥� is a group of magnetic beads coated with Borrelia proteins. Dr. Jewett鈥檚 research has found that those beads will attract the antibodies and provide a clearer indication of infection. 鈥淭he overall goal is new diagnostics and potential new treatments,鈥� she said. 鈥淲e鈥檙e coming at that from a biology standpoint of: If we understand how the bacteria works, we can understand how to stop it.鈥�

The research funding community is taking notice of her work. Days after Dr. Jewett鈥檚 Luminary Series presentation, the National Research Fund for Tick-Borne Diseases (NRFTD) announced she had received a $60,000 grant to further her research into Borrelia Burgdorferi gene regulation, and how the bacteria functions in any given environment.

Dr. Jewett also received an in-house grant from the 性视界传媒 Office of Research and Commercialization. The $7,500 grant is focused on her research into how Borrelia Burgdorferi seeks out nutrients from its host. Her goal is to cut off that process, so that the bacteria will not be able to survive.

Dr. Jewett鈥檚 goal is to change the way Lyme disease is diagnosed, treated and prevented. Her passion for the topic spills over into the classroom, where she is inspiring students to do the same. 鈥淩esearch is my number one love, and bringing teaching into that is how I like to do it, 鈥� she said. 鈥淵es, what you鈥檙e learning is actually applicable, and important and exciting. I think that gives a hands-on meaning to my teaching.鈥�