When Robert Damoiseaux shifted from a career in pharmaceuticals to help launch an open-access technology platform housed at the California NanoSystems Institute at UCLA, it seemed like a switch from industry to academia. But he doesn't see it quite that way.
"CNSI isn't really just academia," said Damoiseaux, director of UCLA's Molecular Screening Shared Resource. "While a lot of clients are based at UCLA, others come to MSSR from all over the world. Pharma likes to use us because we've built a certain reputation, and they know our output. In fact, collaborations with pharma enable us to build tools we otherwise couldn't have, so the advantages go back and forth."
Part of what lured him to UCLA was satisfying his native intellectual restlessness and love of challenge. In his role as MSSR director, he tackles scientific puzzles in numerous interdisciplinary collaborations, befitting a professor with joint appointments in molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and bioengineering at the UCLA Samueli School of Engineering.
"If you figure it out, it's no longer interesting so you find something else to figure out," he said. "We have the tools to take on interesting problems. That keeps me busy and keeps me thinking."
At MSSR, Damoiseaux heads up a facility that supports drug discovery and development as well as basic biological discovery. Investigators can comb through massive libraries of chemical compounds with high-throughput speed thanks to MSSR's staff expertise guiding its advanced, automated machines that run 24/7.
Since its founding in 2004, the facility has built a track record of success, facilitating the move from inquiry into cancer and other diseases to new drugs being tested in the clinic. MSSR's impact is broader still, thanks to the innovative research tools developed by its staff and the unique training available to students.
"We are all about tackling very difficult problems facing humankind," Damoiseaux said. "That's at the center of our mission."
Screening molecules to yield medicines
Damoiseaux speaks with pride of several investigational drugs that got their start at MSSR. For example, a compound called TRE-515 was discovered at MSSR in 2010 and has since been tested in midstage clinical trials at UCLA Health to become — in his words — "our first homegrown, home-discovered, home-tested, home-everything molecule."
Picked from a lineup of 90,000 chemical suspects, TRE-515 inhibits a key enzyme important for producing the building blocks of DNA. That biochemical pathway holds implications for treating a variety of tumors as well as autoimmune diseases. TRE-515 was exclusively licensed to a biopharma company by UCLA Technology Development Group.
"This molecule targets a universal process shared by all cancer cells," Damoiseaux said. "Having a drug with wide applicability is very important from a practical point of view. That it has also been pretty well-tolerated so far is personally satisfying for me. Ideally, we'll make a difference without people having tons of side effects."
Meanwhile, the battle against tropical diseases could get a boost from burkfloxacin, a synthetic molecule identified at MSSR in 2019 as a potential treatment for melioidosis. This sometimes-deadly infection is caused by a bacterium that tends to resist traditional antibiotics.
"With some of our candidates reaching the clinic, we want to do even more in drug discovery," Damoiseaux said. "Driving that forward faster and more effectively is what it's all about for me."
Artificial intelligence and robotics in aid of exploration
Analyzing nearly 500 samples in parallel, with 10,000-plus tested in a day, is work perfectly suited for machines. And at MSSR, automation expands the palette of options for researchers.
"You can run more experiments faster, and you can run new types of experiments," Damoiseaux said. "It also frees us up to think and be productive in other areas."
MSSR makes prodigious use of machine learning, a type of artificial intelligence in which algorithms spot patterns in data that are often impossible for humans to discern.
Among numerous applications, a voice control uses the same kind of large language model that powers chatbots to interpret verbal commands to alter robotic testing routines. AI also conducts image recognition tailored to whatever phenomena is under investigation — vital for making sense of the tens of thousands of images that MSSR instruments can capture in a day. There's even the capacity for users to simply highlight a trait of interest on a touch screen and let an algorithm extrapolate and group similar images.
"That's immensely powerful, and scientists really appreciate it because they don't have to code a thing," Damoiseaux said.
He and his team have even invented a potentially game-changing technology that tightly integrates AI and automation for complete control.
"Our automation gives the ability to measure anything, at any timepoint, with any parameters you choose to evaluate," Damoiseaux said. "We program equipment into the future and tell it precisely what to do. The technology was built around creating flexibility to enable research biology. We've developed a system where all of your experiments can be modified at will — while they are still running. That's a lot of flexibility you don't normally have when using robotics."
A training ground for the scientific workforce of the future
Students working at MSSR get hands-on experience with state-of-the-art instruments and complex investigations in the life sciences. According to Damoiseaux, workforce development activities are motivated by an ethos defined by widening access to high-tech tools.
"We're very democratic around here," he said. "We teach people to take advantage of automation and AI productivity tools that they can't get access to otherwise."
He noted that the training they receive also reaches far beyond technical aspects.
"It's not just, 'Let's train people on some equipment,'" he said. "We're trying to educate the next generation of scientists in a different way of thinking needed for the new types of questions being asked. We aim to bring together in each student scientific competence, team competence and social competence."
The scholarly setting, experiential learning and interface with users beyond academia make for an environment that combines scientific curiosity, professionalism and high standards. Students gain confidence through the practice of producing consistent results day after day.
"We have a culture of the German word, Leistung," Damoiseaux said. "It's difficult to translate into English, but loosely, it means 'performance' in the sense of delivering quality work at a certain rate. It's a word that I cherish.
"Ultimately, people who come out of MSSR have a pretty easy time finding jobs," he added with a smile.
