Abstract: Suppose we successfully isolate and culture a microbe from the soil, a river, or some other environmental source.   Often such microbes are hardy, adapted to a specific role in their ecosystem and the local microbiome, and possess natural abilities to sense or control their environment.   In this talk I discuss the problem of mining novel genetic elements from exotic microbes that respond to a desired signal or analyte, e.g., a pesticide.  We present a data-driven, transcriptomics-centric approach to rank perturbation-inducible genes from time-series RNA sequencing data for the discovery of pesticide-responsive promoters. This provides a set of biomarkers that act as a proxy for the transcriptional state referred to as the cell state. We construct low-dimensional models of gene expression dynamics and rank genes by their ability to capture the perturbation-specific cell state using the method of observability analysis. We show it is possible to extract 15 analyte-responsive promoters for a novel, previously untested organophosphate compound, from over 4000 genes, in the underutilized host organism Pseudomonas fluorescens SBW25. Furthermore, we enhance malathion reporting through the aggregation of the response of individual reporters with a synthetic consortium approach and we exemplify the library’s ability to be useful outside the lab by detecting malathion in the environment.

BIO: Enoch Yeung is an Assistant Professor in the Department of Mechanical Engineering at the University of California Santa Barbara.    He is the director of the Biological Control Laboratory, which is an interdisciplinary laboratory that aims to bring together expertise in control theory, synthetic biology, and systems biology to develop new mechanisms for biological control and computing.   Prior to his appointment at UCSB, Enoch was a Senior Research Scientist at the Pacific Northwest National Laboratory.  He holds a PhD in Control and Dynamical Systems from the California Institute of Technology and is the recipient of the NSF CAREER award, the Army Young Investigator Program award, and a Keck Foundation award.