Paul O’Maille

Program Director, Biocomplexity Sciences

Dr. O’Maille leads a multidisciplinary life-science research program at SRI in the areas of biodefence, precision medicine and biotechnology. For over two decades, Dr. O’Maille has amassed deep domain knowledge in a broad range of disciplines including protein engineering, molecular evolution, biophysics, bioinformatics, systems biology, metabolism and microbiology. His approach is typified by combining tools and concepts from multiple disciplines to devise creative solutions. Dr. O’Maille’s central research interest is the relentless pursuit of genotype-phenotype prediction – decoding the effect of genetic changes (mutations) on traits at the biochemical and organismal levels. This carries real-world implications that propagate across scales of biological organization – from predicting the emergence of viral pandemics and adverse drug responses in the human population to chemical ecology.

Dr. O’Maille has a distinguished record of secured funding from diverse sources including IARPA, DARPA, NSF, NIH and BBSRC (UK). He currently leads SRI teams on both fundamental and applied science projects. This includes the DARPA Measuring Biological Aptitude (MBA) program where his team is building next generation precision wearables to capture physiological readouts of human performance and resilience in warfighters. He also leads an SRI effort to build a ‘Rosetta stone’ for insect chemical communication funded by NSF. Most recently, he was awarded an NSF RAPID project to uncover new insights into how SARS-CoV-2 and other viruses mimic human biology as strategies for host infection and adaptation.

A fervent Buckeyes fan all his life, Dr. O’Maille earned his Ph.D. at The Ohio State University, supported by an NIH research fellowship award. Moving on to the Salk Institute for Biological Sciences, he was both an NIH and HHMI postdoctoral fellow, receiving the Outstanding Scientific Presentation Award (Salk Research Fellows). Since then, he has given over 40 invited lectures worldwide. Following his postdoc, Dr. O’Maille led a research group jointly at the John Innes Centre (JIC) and the Institute of Food Research (IFR) in the UK before coming to SRI. At JIC, Dr. O’Maille’s lab uncovered the emergence of cyclization in plants – a biochemical trait that endowed plants with a rich source of chemical diversity for pathogen defenses, chemical communication and environmental adaptation. His IFR group investigated the mode of action of dietary phytochemicals (plant natural products) and antibiotics.

Recent publications

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Emergence of terpene chemical communication in insects: Evolutionary recruitment of isoprenoid metabolism (3/28/2023) We present the first structural and mechanistic model for the evolutionary emergence of TPS function in insects. Through identifying key…
Ancient origin and conserved gene function in terpene pheromone and defense evolution of stink bugs and hemipteran insects  (1/15/2023) The origin of enzymes involved in terpene biosynthesis and their evolution in insect genomes is still poorly understood. We addressed…
Sparse epistatic patterns in the evolution of terpene synthases (7/7/2020) We explore sequence determinants of enzyme activity and specificity in a major enzyme family of terpene synthases.

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