James L. McGaugh Distinguished Seminar Series

Tuesday, April 15, 2025 at 11:00am

The seminar will be In-Person.

Coleen T. Murphy, PhD

James A. Elkins, Jr. Professor in the Life Sciences and Director

LSI Genomics, Princeton University​

“Adapt or Die: Transgenerational Inheritance of Pathogen Avoidance (How getting food poisoning might save your species”

Abstract:

Caenorhabditis elegans must distinguish pathogens from nutritious food sources among the many bacteria to which it is exposed in its environment. We found that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance in the treated worms and in four subsequent generations of progeny. The RNA interference (RNAi) and PIWI-interacting RNA (piRNA) pathways, the germline and the ASI neuron are all required for avoidance behaviour induced by bacterial small RNAs, and for the transgenerational inheritance of this behavior. A single P. aeruginosa non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. Our results suggest that this non-coding-RNA-dependent mechanism evolved to survey the microbial environment of the worm, use this information to make appropriate behavioral decisions and pass this information on to its progeny.

Bio:

Coleen T. Murphy is the Director of LSI Genomics and the James A. Elkins, Jr. Professor in the Life Sciences in Molecular Biology at Princeton University. She graduated from the University of Houston with a B.S. in Biochemistry and Biophysics, then earned her doctorate in Biochemistry at Stanford University, studying the structure-function determinants of pre-steady state kinetics and motility of the motor protein myosin. During her postdoctoral work at UCSF, Dr. Murphy built C. elegans microarrays and used them to identify the set of genes downstream of the insulin signaling/FOXO longevity pathway. This work revealed that insulin signaling coordinates the expression of a vast array of downstream cellular processes, including stress response, proteostasis, metabolism, immunity, autophagy, and intercellular signaling, to extend cellular and organismal maintenance with age.

In her own lab, Dr. Murphy’s team has developed C. elegans models of human “quality of life” aging phenotypes, including cognitive aging and reproductive aging, using genetic, genomic, and microfluidic approaches; they have identified genetic pathways that can extend each of these processes with age. At the molecular level, these processes are remarkably well-conserved through humans. Dr. Murphy’s team has developed new genomic approaches to isolate and transcriptionally profile all of C. elegans’ adult cells, in order to better utilize this system as a model for human disease, and developed assays to model human neurodegenerative disease, including learning, memory, and movement disorders. Her team showed that a memory pathway they first identified to rescue memory in old worms can also rescue memory in old mice, using the same molecular pathways. Dr. Murphy’s lab also made the surprising discovery that mating induces rapid post-reproductive aging, utilizing the same genetic pathways that extend longevity. Her lab discovered that C. elegans can interpret the small RNA code of the bacteria that they ingest to direct an avoidance response, and that information can be transmitted transgenerationally. Her group has now shown that this mechanism is conserved in wild bacteria and wild C. elegans strains.

Murphy’s awards for her research include being named a Pew Scholar, March of Dimes Basil O’Connor Scholar, Keck Scholar, McKnight Fellow, Sloan Fellow, Glenn Medical Research Foundation awardee, Howard Hughes Medical Institute- Simons Faculty Scholar, AAAS Fellow, and she was awarded the New Innovator, Transformative R01, and two Pioneer awards from the NIH Director’s office. She has won both the Women in Cell Biology Junior and Mid-Career Awards for Excellence in Research from the American Society for Cell Biology. She is the Director of the Glenn Foundation for Research on Aging at Princeton, and she is the Director of the Simons Collaboration on Plasticity in the Aging Brain, and is the author of the book, “How We Age” (Princeton University Press), a 2024 PROSE Finalist.