Computing a Response to COVID-19

By Kimberley Clementi

Not many people were thinking about antibodies in 2019. Back then, if the average person even contemplated the human body’s response to infectious disease, it was likely only to consider preventative and palliative care – immune boosters like zinc, elderberry, Vitamin C and plenty of rest.

Natalie Castellana (Ph.D. ’12) was the exception. When COVID-19 brought antibodies to the forefront of the pandemic discussion, Castellana was well ahead of the curve. She had been studying antibodies for over a decade and, in 2009, founded Abterra Biosciences (formerly Digital Proteomics) to translate innovations in bioinformatics into applications for the pharmaceutical and biotech industries.

Leading the Science

Throughout 2020, while world leaders looked to science to inform their response to COVID-19, Castellana viewed the pandemic from a parallel perspective. The UC San Diego Computer Science and Engineering graduate and CEO of Abterra Bio believed that computer science, in conjunction with other scientific fields, had a critical role to play in ameliorating the global health crisis.

Prior to the pandemic, Castellana and her team at Abterra Bio – including two CSE classmates, Stefano Bonissone and Anand Patel – were already looking to computer science to deconvolute the adaptive immune response to infectious diseases. They had developed a platform, Alicanto®, that uses mass spectrometry and next generation sequencing to rapidly identify which proteins could be most effective in neutralizing viruses. When COVID-19 emerged, Castellana recognized that Abterra Bio’s innovations were relevant and timely.

“COVID happened. And it happened to be right in our path – our line of sight,” Castellana says. “We were already looking at finding antibodies that have therapeutic potential by looking directly at people who had overcome a disease. So it was not that hard to recognize that we should do this for COVID, too.” 

Throughout the pandemic, Abterra Bio worked with the San Diego Blood Bank to obtain blood samples from local San Diego patients who had recovered from COVID-19. The company then analyzed these samples for virus-neutralizing antibodies. While the research is ongoing, Castellana is intrigued by the challenge COVID-19 variants present to therapeutic treatments and believes her team can help.

“With our approach, we can look at an antibody protein directly. We can pick out an individual antibody and determine whether it is neutralizing all the different variants or just a subset,” says Castellana.

Not only can Castellana’s team identify promising antibodies, but they can find them faster.  Abterra Bio’s platform employs algorithmic and machine learning approaches to accelerate the pace of biological research, which can otherwise be like looking for the proverbial “needle in a haystack.” Computer science, and the computational speed it provides, could potentially shorten the timeline to develop new treatments and drugs.

“While biology is not any different now than 100 years ago, we now have better tools to understand the science,” Castellana explains. “That’s what drives innovation, the technology.”

Harnessing Protein Power

Technology is only one aspect of Castellana and Abterra Bio’s groundbreaking work. Their interdisciplinary team of data scientists and biologists are pushing the boundaries of bioinformatics by starting with a different thesis: one based in proteomics rather than genomics.

Treating infectious diseases like measles and diphtheria, and now COVID-19, generally follows the long-proven method of using antibodies from survivors of the disease. Most studies then focus on gene sequencing and look at the B cells that produce antibodies. The challenge is that B cells can be exceedingly rare and elusive, or even irrelevant, to overcoming the disease.

In contrast, Abterra Bio’s platform, Alicanto®, mines the antibody proteins directly. This allows researchers to examine the antibody molecule and the proteins within an organism. It’s a game-changer in the way science tackles potentially deadly diseases – one that essentially harnesses the power of the human immune response system. 

“Every human generates billions of different antibodies to a variety of different challenges, from vaccines to pathogens to cancer cells,” says Castellana. “Our technology is built to identify the antibodies that have been fully optimized by the immune system and therefore are nature’s solution to overcoming a disease.”

Sequencing a Company’s Path

As Castellana looks to the future, she is optimistic Abterra Bio’s technology will not only impact treatment of infectious diseases but oncology as well. Over the next two years, the company will continue validating and extending their platforms and will soon have antibodies in preclinical development for several therapeutic areas. 

While the road ahead looks promising, Castellana is quick to recognize that Abterra Bio is building on research and algorithms conceived a decade earlier at CSE. She credits her co-founders and advisors, CSE Professors Pavel Pevzner, Vineet Bafna and Nuno Bandeira for their ground-breaking work in bioinformatics and computational tools. 

“From their pioneering work, a variety of tools emerged – from sequencing antibodies directly from the protein, to using next generation sequencing to look at patient response to disease, to trying to find virus neutralizing antibodies,” she said. “A whole body of work came out of their labs. And that’s where the company started – with the technology developed from UCSD.”

In addition to licensing intellectual property to Abterra Bio, UC San Diego has provided support to commercialize the fledgling company’s technology. The company worked with UC San Diego Office of Innovation and Commercialization to license software and patents developed by the campus team. 

Castellana acknowledges one more valuable legacy from CSE: its interdisciplinary learning environment. She describes CSE as “entrepreneurial” and “collaborative across disciplines” – a combination Castellana has replicated at Abterra Bio, noting almost all the company’s employees come from the amazing talent pool at UC San Diego across a variety of disciplines. 

“One thing I thoroughly enjoyed about CSE was the opportunity for interaction across subfields within computer science. It was exciting to be just down the hall from world class research in cryptography, computer graphics, and machine learning,” says Castellana. “Exposure to people thinking about things in different ways is so important to innovation.”

For Castellana, applying her computer science background to biological problems was more than a cross disciplinary approach to problem solving. It was personal, too. As Castellana is fond of saying, she wanted to be a “computer scientist with a soul.” 

“I knew I wanted to switch into bioinformatics, to apply my knowledge about computer science to biological problems,” says Castellana. “How do we live healthier and fuller lives? That was the answer I wanted to solve.”