UT researchers help sequence genome of plant with cancer treatment potential

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Photo Credit: Courtesy of Bob Jansen

In the hands of scientists, a poisonous shrub could play an integral role in certain chemotherapy treatments and possesses potential for future cancer therapies.

UT professors have sequenced the DNA of Rhazya stricta, one of the species of plants in the Apocynaceae family. The project, which involved a collaboration between universities in Saudi Arabia, Canada and the United States, began in 2011.

R. stricta is a common wild plant in Saudi Arabia and produces compounds called alkaloids. Alkaloids are naturally occurring products in plants that cause either positive or negative physiological responses in humans. Nicotine, caffeine, and morphine are also alkaloids.

Scientists currently use alkaloids from other plants in the milkweed family in chemotherapy treatments for diseases such as leukemia.

Due to R. stricta’s complex metabolic pathways, scientists have not been able to create the alkaloids synthetically. They have only been able to extract the alkaloids from the plant itself, according to Tracey Ruhlman, research associate in the Department of Integrative Biology.

“You watch animals and developing cultures who live in these areas and how they use flora to treat their illnesses or disinfect their water or put a bandage on the wound,” Ruhlman said. “Now, more contemporary scientists want to understand how active materials are actually doing this business of healing.”

According to Ruhlman, R. stricta could be a great resource for medicine, and understanding its genomic sequence can help researchers compare it to other plants. 

“We can learn how to manipulate it, potentially produce higher amounts of those materials we’re interested in, or produce them in other organisms,” Ruhlman said. “But without the information, you can’t even begin to do any of those things.”

For scientists to use R. stricta for therapeutic applications, they must know the plant’s genetic sequence and its evolution compared to others’ in its family, said UT integrative biology professor Robert Jansen.

“You need to have the resources of knowing the genomic information, of how genes have evolved to have the potential to exploit the pathways of the compounds in the future,” Jansen said.

Jansen said the King Abdulaziz University in Saudi Arabia reached out to him because the university was interested in investing in science and education. 

“I think there’s interest in many countries in bioprospecting, in exploring the native flora and fauna for therapeutic potential,” Jansen said. 

King Abdulaziz University funded the study, but researchers used a variety of UT resources, including the bioinformatics team, Jansen said. 

Early on in the project, Jansen teamed up with Dhivya Arasappan, a research scientist for UT’s Center for Computational Biology and Bioinformatics. Arasappan helped brainstorm what type of data to generate and assisted with assembly and annotation, or identification of significant portions, of the DNA.

The data consisted of fragments, which included various DNA sequences. According to Arasappan, two different techniques were used to display the genomic data: one of higher quality, which displayed fewer, larger fragments, and one with lower quality.

These fragments were then combined through protein assembly to form an entire R. stricta genome size file, which describes what the genome of R. stricta looks like.

“It’s kind of like putting a puzzle back together and trying to figure out which sequence comes next and which sequence overlaps with which sequence,” Arasappan said. “So we have all the little puzzle pieces that we have to put back together into a scaffold.”

The next steps for this study use this complete genome of R. stricta to isolate specific components for research, Jansen said. In other studies, the plant has been tested for its tolerance to extreme conditions, such as drought.

“The group we’re working with is actually taking it further by isolating specific compounds and doing animal studies, such as with mice who have cancer,” Jansen said. “So that’s the next step.”