Jacobs School Researchers Capture ASPIRE Challenge

By Bill Bruton

Their victory came in the National Center for Advancing Translational Sciences (NCATS) ASPIRE (A Specialized Platform for Innovative Research Exploration) Reduction-to-Practice Challenge.

Their winning research project, titled “Iterative Learning and Automated Modular Platform for Optimum Nonaddictive Analgesic Discovery,” focuses on helping to solve the opioid crisis in the U.S.

“This is a challenge, not a grant. It started in 2019 with a design challenge. After that, there were multiple milestones. The second and third milestones happened in 2021 and 2022, respectively, and when we ended up at the end of milepost three, there was one group left standing,” says Ram Samudrala, PhD, professor of biomedical informatics, chief of its Division of Bioinformatics and co-principal investigator on the project. “It was a process that kept whittling down competitors. It started with hundreds, then got cut to 10 teams, then five, four, three, two and finally, one. It was kind of like the World Cup.”

The NCATS ASPIRE Challenges are part of the Helping to End Addiction Long-Term Initiative (NIH HEAL) to speed scientific solutions to the national opioid public health crisis.

The Challenge solution consists of four mandatory components: (1) a comprehensive database of chemicals; (2) an open-source electronic lab notebook; (3) an advanced machine learning platform; and (4) a high-throughput system for relevant biological assays.

“We already had elements of all four components in place to start the challenge. We hadn’t thought of applying it to opioid-related problems, but when we saw this opportunity, we took it. You need these kind of innovative challenges by NCATS to get out-of-the-box ideas, more publicity and more funding to keep it going,” Samudrala says.

Gaurav Chopra, PhD, was co-PI on the project. He worked with Samudrala in implementing a platform called CANDO (Computational Analysis of Novel Drug Opportunities) as a mentee and is continuing in the research as an associate professor of analytical and physical chemistry in the Department of Chemistry at Purdue University. Chopra’s laboratory also developed the CIPHER database, which comprised component 1 of the challenge.

Samudrala recruited other members of the Jacobs School to the team. They included Zackary M. Falls, PhD, a postdoctoral fellow at the time of the CANDO research and now an assistant professor of biomedical informatics; and two pain addiction experts from the Department of Pharmacology and Toxicology: Jun-Xu Li, MD, PhD, professor, and Panayotis Thanos, PhD, senior research scientist.

Chopra put together a team from Purdue that included colleague R. Graham Cooks, PhD, inventor of the DESI-MS high throughput system, which made up component 4.

He also brought in Connor W. Coley, PhD, assistant professor at Massachusetts Institute of Technology, developer of the ASKCOS software package and a predictive chemistry expert, rounding off component 3.

Runner-up in the competition was a group of researchers from Arizona State University, CiBots Inc., University of Glasgow, University of California-San Diego and Visionary Pharmaceuticals Inc. with their project “Closed Loop Bio Assay-Chemputer for Next Generation Analgestics (BioChemputer).”

“They were very strong competition, but in the end we were able to beat them out, and that was very satisfying, because they had been working on this for a very long time, while we just started with the opioid research when the competition came out,” Samudrala says. “There were three milestones in the challenge and each time we were ranked at the very top, which was only possible due to the hard work of the students and trainees.”

Samudrala and his team earned $100,000 in the first design challenge in 2020 and $1.22 million in subsequent challenges for a total of $1.32 million in funding.

The funding will help continue research to help solve the opioid crisis.

“Now we have a full program established in opioid-overuse disorder and opioid rescue, but that was only possible with this funding. It wouldn’t have been possible by a traditional granting method,” Samudrala says. “It’s a great feeling. The team was excellent. It’s really a credit to all the students. The PIs are one thing, but it was really the graduate students and the postdocs who did all the hard work on this project.”

Others from the Department of Biomedical Informatics who contributed to the winning project were:

• William Thomas Mangione, PhD, research scientist
• Brennan Overhoff, research assistant