Karishma Kalera came to Central Michigan University from India ready for a fight.
biochemistry, cellular and molecular biology doctoral student has joined the battle being waged against tuberculosis by an international team of students assembled by
chemistry and biochemistry faculty member Ben Swarts in the
College of Science and Engineering.
Among the team members are fellow BCMB doctoral student Nicholas Banahene from Ghana, and undergraduate biochemistry majors Alicyn Stothard, from Coleman, and Dan Gepford, from Farwell, both in Michigan.
Their rich mixture of skills and experience is what gives the team its strength and is the hallmark of CMU research, Swarts said.
"At CMU, undergraduates get the opportunity to make significant contributions to research projects and to publish their work," Swarts said. "And the fact that we are doing research with a global reach helps to put us on the map and generates interest from talented students from around the world."
TB's worldwide toll
The battle against TB is imperative. About 2 billion people worldwide are infected with the TB bacterium — mycobacterium tuberculosis, abbreviated MTB — which causes the disease that killed more than 1.6 million people in 2017.
Not everyone who is infected by MTB develops the disease, though. In about one-quarter of the world's population with TB, the bacterium remains dormant. However, about 10 percent of those with "latent TB" develop active TB at some point in their lives.
Ineffective diagnostic tools and treatments
While a culture test is the gold standard for diagnosing TB, it is not ideal because the disease is so slow growing that it can take weeks to get an answer — and up to a couple of months for the more drug-resistant forms.
Once a diagnosis is finally determined, it can then take six or more months to fully treat TB with a regimen of three or four antibiotics with undesirable side effects. Therefore, many people stop taking the drugs within a few weeks as they start to feel better, which can lead to drug-resistant strains of TB that are extremely difficult to diagnose and treat.
Attacking the envelope
Swarts and his team are working to improve TB drugs, diagnostic tools and vaccines. The research has been funded by more than $1 million since 2013 by the
National Institutes of Health, the
National Science Foundation, the
Research Corporation for Science Advancement, and the
Camille and Henry Dreyfus Foundation, he said
As chemists, they are focusing their efforts on the "cell envelope" of the bacterium, which is its spear and shield, Swarts said.
Specifically, they are designing chemical compounds that will shut down the cell envelope and keep it from growing and spreading, or will create an open door for a vaccine or similar treatment to enter, he said.
Doing that requires a unique skill set.
"We are one of just a few labs that can make new compounds as well as test and apply them, then make them available to other TB researchers who don't have that capacity. So, we have a lot of collaborations going on with scientists around the world."
Undergrads get early exposure to research
Undergraduates are not allowed to work with the actual TB bacteria because of its deadly potential, so they work with non-pathogenic model organisms that help the researchers apply and evaluate the compounds safely.
That early exposure to applied research is key to building a student's research skills and confidence, Swarts said.
"This really differentiates us from most other universities." — Ben Swarts, chemistry and biochemistry faculty member
To ensure that students get a chance to learn those skills, every chemistry and biochemistry major is required to take Chemistry 491, an in-depth capstone research course that links them up with a faculty mentor to work one-on-one to come up with a project, get the required training, execute the project and write an undergraduate thesis.
"We encourage them to start early in research because it gives them opportunities to publish their work, which opens all kinds of doors at the next level," Swarts said. "Alumni tell us over and over again that this research experience is the most impactful thing that they did."
Gepford and Stothard appreciate being able to take part in the global research.
"It's great to be on a team that is working on such a large goal, knowing that everything you are doing makes a difference," Gepford said, who plans to apply to the BCMB doctoral program.
"This is an extremely important project," Stothard said. "I feel fortunate to be putting out building blocks for others to build upon. One group cannot cure TB on its own."
The fight is personal
Both Kalera and Banahene entered the doctoral program specifically to work in Swarts' lab. For them, the fight against TB is personal. They both come from countries where funding to diagnose and treat the disease is much less than in the United States.
"I put all my effort into my work because of the great need of people in under-resourced areas like the people in my region," said, Banahene, who is the first in his farming family of nine to attend college. "I am working toward something bigger."
"To see people still dying from this disease is very distressing," Kalera said.
They both want to be an example for others living in their home regions to strive to make a difference.
"It doesn't matter where you were born or what you are facing, you can go somewhere and do something meaningful in your life," Banahene said.
Taking research to the next level
Swarts expects that by next semester the team's applied research will kick up another notch with the opening of a
biosafety level-three facility, which requires a set of precautions that have to be taken to safely work with hazardous organisms in a specially designed facility.
The lab enables specially trained doctoral and post-doctoral students to conduct research on the TB bacterium directly rather than model organisms, Swarts said.
"This really differentiates us from most other peer institutions," Swarts said. "It signifies the high level of research that CMU is doing."