Research with global impact

Pro Futuris, the University’s strategic vision, reminds us that we are “compelled to care for one another and to address the challenges of our hurting world.” In Baylor’s prehealth studies program, undergraduate and graduate students experience research alongside three faculty members who are dedicating their knowledge and expertise to solving one of the world’s health issues—neglected tropical diseases (NTDs). The professors are conducting research projects in their laboratories on campus with the hope of developing vaccines, medications and plants which could help eradicate malaria, lymphatic filariasis, dengue and Chagas disease.

The World Health Organization’s statistics on these and other NTDs might be difficult to fathom by people in the U.S. where vaccines and medications seem so prevalent, but these diseases exist in more than 100 countries worldwide and reinforce a cycle of poverty in disadvantaged populations. Today, about 3.3 billion people, half of the world’s population, are at risk for being infected by malaria; 50 to 100 million infections of dengue are estimated to occur annually; and 16 to 18 million people are affected annually by Chagas disease.

“Global health and neglected infectious diseases are one of the most significant challenges of our generation,” says Dr. Cheolho Sim, assistant professor of biology. “Yet, at the same time, they can be overcome. Without a doubt, this fact keeps me motivated to continue my research. This generation can solve this crisis.”

Specifically, Sim and his colleagues in the Baylor College of Arts and Sciences are fighting vector-borne diseases transmitted by insects such as mosquitoes, flies and bugs:

• Vector biologist and genomics expert Sim is developing transmission-blocking vaccines through transcriptome (the RNA transcripts of the genes of a cell or organism) analysis of the Brugia parasite, transmitted by mosquitoes.
• Molecular biologist Chris Kearney, associate professor of biology, is making genetically engineered impatiens that can kill mosquitoes carrying NTDs.
• Dr. Mary Lynn Trawick, associate professor in chemistry and biochemistry, is developing a new drug to block a particular enzyme that is required throughout the lifecycle of the parasite in Chagas disease. The idea is to block the enzyme and kill the parasite.

Different approaches and collaborations with other scientists around the world are vital to solving this global health crisis. One person’s discovery can spark a new research direction for another and so on. All three of these researchers point to other studies that initiated their projects and often resulted in numerous collaborations.

“This is really the way world-class research is done these days,” says Dr. Truell W. Hyde, vice provost for research at Baylor. “You no longer compete; you collaborate.”

Golden Age of Vector Biology

A South Korean native, Sim came to Baylor four years ago after completing postdoctoral work at The Ohio State University. After observing Baylor faculty members, he noticed “an extreme devotion to their calling.”

“I couldn’t recall seeing that level of devotion at other schools where I had interviewed,” Sim says. “What attracted me was an opportunity to work at a university where you can live out your faith and be a very productive researcher. Additionally, my research field needs a sense of calling. Since I’ve joined Baylor, I’ve found that many students want to devote their lives to addressing these global issues as well.”

As a graduate student working on his doctoral degree at the University of Notre Dame, Sim specialized in new approaches in vector control and was involved in using whole genome sequences of disease vectors. He has since used genome studies of disease vectors to try to block infectious pathogens.

Sim is often recruited to use his expertise on various genome projects including the tsetse fly genome project, which took 10 years to complete with the collaboration of 150 scientists worldwide. His role was to discover the function of each of the 20,000 genes that make up the tsetse fly. In describing a genome, Sim compares it to a Google map giving scientists much needed directions to the subject’s genes. In order to develop a vaccine target antigen, the researcher must find the target genes that express those proteins. Without a map, the researcher cannot find the right location of those genes on the chromosome.

The genome is the infrastructure needed to conduct research, to develop vaccines or pesticides. It is a tremendous resource for all scientists. While many vector genome projects are ongoing, the mosquito genome was completed four years ago and the tsetse fly was completed this year. Each step is considered a major accomplishment.

Sim’s other research focus concerns diapause, a dormancy period of mosquitoes and other disease vectors occurring in the winter. The basic science of how they regulate this seasonal development is lacking. Sim believes that somehow during this period, the West Nile virus replications are suppressed. In the spring, they can begin transmitting the virus again. Understanding the molecular regulation of diapause could be a path to disrupting the West Nile virus transmission cycle. The goal is to control the diapause.

“Science is not a 100-meter race; it is a marathon,” Sim says. “This type of research requires commitment, not just one or two years of research, but a lifetime of research. This is what I want to do with my life. The first steps are being taken now. I can truly say that this is the golden age of vector biology.”

Plant Biotechnology

Dr. Kearney, who joined the Baylor faculty 20 years ago, decided in 2005 to make a shift in his research, which to that point had focused on plant viruses and cancer research. He found an interest in NTDs. Using his expertise in plant viruses he looked closely at plant biotechnology, strongly influenced by his undergraduate and graduate students at Baylor who were interested in medicine.

“I realized with plant biotechnology, we can produce medicine like we do in mammalian cells, insect cells or with bacteria or yeast. But we can produce them much more cheaply because we can simply grow the plant,” Kearney explains.

As he continued to learn more about plant medicines he began to wonder, ‘Was there something that plants can do that nothing else can do?’ He soon discovered that he was the only one looking at this particular question. As part of Sim’s Baylor interview process, Kearney listened to Sim’s research on mosquitoes and that led Kearney to begin looking at the nectar in plants that attract mosquitoes. He also came across a study that found an element called the promoter operating in the plant’s nectary (where nectar is produced).

Kearney came to realize that he could produce something—a toxin—in nectar and that mosquitoes would pick it up and die. As with most research, each discovery brought a new piece of the puzzle to light. Through those steps, he eventually formed collaborations with four scholars, each with an important piece to the puzzle.

“We looked at all kinds of plants in my lab, and we found one that produces prodigious amounts of nectar, and the nectar has a lot of a particular protein so we can hijack the promoter for that protein and express the toxin. We checked the ability of this toxin to kill adult mosquitoes, and we found that the mosquitoes were extremely attracted to this plant,” Kearney says, noting he is preparing a manuscript on the research for publication.

“We are making genetically engineered impatiens that can kill mosquitoes. No load on the environment and no pesticides,” he says.

Kearney is quick to point out that the impatiens will be a model system designed to work well in the lab, but may also work in native climates where mosquitoes carrying malaria and dengue are prevalent, especially since 800 different species of impatiens exist worldwide and are mostly considered tropical.

“It really comes down to a problem of horticulture,” he says. “If we can get this model system to work as well as it seems like it’s going to work, it’s just a matter of working with local scientists. It’s really their job. This is what I hope for the future. I would love to work with scientists in the Southern Hemisphere to support in any way I can.

“This is what Baylor is all about. It is not to be arrogant but to come in with something that is appropriate and work with them—to empower them. Of course, it is science, so it may not work. If 100 of us try solutions that are very innovative, then there will be five or 10 of us that win, and that’s OK, because, if 100 of us do not try, no one wins.”

In May, Kearney participated in an Accelerated Commercialization Program through the LAUNCH Innovative Business Accelerator in the Baylor Research and Innovation Collaborative (BRIC). The program assists inventors and early-stage startups with honing in on goals, plans and strategy. Kearney says, “I love research, but for me it’s important that what I do is actually used by someone and will actually help someone.”

Biochemistry

Initially, Trawick was attracted to Baylor because of the opportunity it gave her to teach biochemistry in a chemistry department. Fast forward 30 years and today, she continues to teach biochemistry in what is now the Department of Chemistry and Biochemistry and manages a biochemistry lab, aptly named the Trawick Group.

As a witness to three decades of change, Trawick says Baylor has always been supportive of her research, providing instrumentation when needed, offering sabbaticals and funding post-doctoral associates and undergraduates. In addition, the University has been supportive of undergraduate students participating in the laboratory, which has always been important to Trawick, since her experience as an undergraduate in a summer research project sparked her interest in research.

“I have had undergraduates working in my laboratory from the very first year,” she says. “It is a privilege to get to know the students, and we’ve had some wonderful students in the laboratory through the years. Many of them have gone on to medical or graduate school or biotech companies. A research experience either during the semester or during the summer is extraordinarily important, and Baylor has always supported that.”

These students are exposed to numerous research projects being conducted simultaneously in the Trawick Group, located in the Baylor Sciences Building. The lab concentrates on the design and evaluation of new compounds as therapeutic agents through enzyme kinetics and assays, mammalian cell culture, molecular modeling and protein purification. Currently, two of the projects focus on cancer research and a third centers on the development of a new drug to treat Chagas and other parasitic diseases.

The Chagas disease project stemmed from a graduate student’s seminar concerning research on the disease which mentioned a certain enzyme that turned out to be a therapeutic target for the disease. If the enzyme, which is required throughout the lifecycle of the parasite, is blocked, the parasite would die, and the disease would be cured. Trawick is looking at ways to block this enzyme’s activity.

The parasite in Chagas resides in the triatomine bug, sometimes called the kissing bug. When taking its blood meal from a human, it deposits the parasite in the wound. In the acute stages of the disease, Chagas can be cured, but in the chronic stages there is no effective treatment. This particular NTD is also one of the major causes of heart disease in Latin America.

Trawick also collaborates with Dr. Kevin G. Pinney, professor of chemistry at Baylor, on two cancer research projects. In the first one, they are targeting the tubulin microtubule system, which changes the shape of cells and prevents rapid cell division by tumors. In the second one, the enzyme being targeted for Chagas disease could be the key to inhibiting cancer metastasis or arresting cancer metastasis.

“As the health of populations in developing countries becomes better, people are living longer and cancer certainly increases with age,” Trawick says, “and so we are finding an increase in incidents of cancer worldwide. These cancer projects certainly have global implications.”

For the Love of Teaching

Sim, Kearney and Trawick speak passionately about their projects and the opportunities to make a difference on the world’s global health front. They also speak enthusiastically about their students. Of course, the faculty-student interaction model in the prehealth studies program is found across all disciplines at Baylor.

“If you look across campus, faculty members go out of their way because inherently they love to teach,” Hyde says. “They are good teachers, good researchers, and good scholars. They are exceptional in all of those areas. They are excited to share their knowledge with their students; couple that with a mission that drives them from the standpoint of the Christian nature, and the experience is only enhanced.”

If students think they are getting the better end of the deal in these relationships, they might be surprised to discover the professors have a different take. The faculty members gain new perspectives, continued motivation and validation from working with the students.

“I find interacting with my colleagues and students intellectually stimulating,” Trawick says. “We’re always finding out new things about cells for example and that’s fascinating—to find out something that no one else has ever discovered before. It is also very rewarding when a student understands the big picture or a complex experiment. It’s even more rewarding when a student can suggest a new experiment, which shows that he has gained enough insight to ask questions for himself.”

For Kearney, teaching students the scientific method is energizing. He notes science allows a group of disparate people—from various countries and religions—to agree to admit they are wrong if the data shows they are wrong.

“We all agree to certain ideas, such as having a formal hypothesis and sticking to that hypothesis,” he says. “It’s fun to work with students and strap yourself into that seat with them and agree that this is the way we are going to go. This is what I appreciate more and more, working with students and teaching them the scientific method. That’s really fun.”

The Future Looks Bright

From its faculty to its facilities, the College of Arts and Sciences has a strong prehealth program attracting students interested in pursuing careers in eight areas of healthcare such as premedical, pre-dental, pre-physician assistant and pre-optometry.

“Many of our faculty in the Departments of Biology, Chemistry and Biochemistry, Psychology and Neuroscience, Environmental Science and Statistical Sciences conduct research on health-related topics,” says Dr. Lee C. Nordt, dean of the college. “These departments, along with our innovative medical humanities program, typically focus their efforts on basic to translational cancer research and on research involving pharmaceuticals and tropical diseases.”

The college is leading the research collaboration with the National School of Tropical Medicine in the Baylor College of Medicine, particularly in biology and biomedical sciences. The creation of the new College of Health and Human Sciences (see related article, p. 3) will expand and enhance research collaboration, explains Dr. Richard Sanker, director of prehealth studies at Baylor.

“Our intention is to expand the research and educational programming to include topics in global health and possibly to create a diploma in missionary medicine and health for nursing and other healthcare professionals planning to embark on missions to developing countries.”

With this type of teaching, research and scholarship as a foundation, Baylor faculty, students and staff will continue to strive to find answers to help our hurting world and to have an impact in the world community in which they live.