Event
Bioengineering Seminar Series: Daniel Dwyer
Friday, January 30, 2015
9:00 a.m.
Pepco Room (1105), Jeong H. Kim Engineering Building
Alyssa Wolice
awolice@umd.edu
Daniel Dwyer
Assistant Professor
Department of Cell Biology & Molecular Genetics
University of Maryland
Application of biomimetic RNA synthetic biology devices to the investigation of antibiotic resistance
The declared goal of synthetic biology remains the rational engineering of biological systems that exhibit novel features and perform within operational design specifications to deliver a defined output. The still maturing field has largely relied upon the assembly of well-characterized biological molecules into increasingly complex arrays for proof-of-principal studies demonstrating that prescribed functions can be achieved with orthogonality. While such efforts have illustrated that ectopic biological circuits can execute quantifiable, logic-based tasks that are tolerated by the homeostatic processes of model organisms, there are few examples outside of metabolic engineering where synthetic biology has been functionally applied to address biological questions.
My research interests lie in the re-engineering of natural systems, and capitalization on natural design principles, to develop novel, high-throughput experimental tools that facilitate challenging experiments and generate high-resolution data. The questions I am motivated to address with this approach are related to elucidating mechanistic details of the cell death process induced by lethal stress in bacterial pathogens underlying infectious disease. Surprisingly, the specific sequences of events leading to cell death (or tolerance) elicited by the functionally diverse range of antibiotic therapies remain underappreciated, as do the participants in these events. We hypothesize that these events, including metabolic remodeling induced by lethal stress, is deterministic in nature and will provide a blueprint for enhancing antibiotic therapies.
To gain novel insight into the genetic and molecular mechanisms of pathogen cell death we are developing synthetic RNA-based experimental platforms to characterize lethal stress-enriched genes, alter the behavior of lethal stress-activated gene networks and reprogram lethal stress-induced metabolic responses. One approach we are taking is to utilize our previously described, modular RNA synthetic biology platform for post-transcriptional regulation of bacterial gene expression that uses engineered, dynamic structural characteristics to both silence and activate gene of interest expression. Several advantages of this “riboregulation” platform have been demonstrated, including leakage minimization, rapid response kinetics, tunable activation, physiologically relevant protein production, component modularity and the ability to orthogonally control multiple genes. We anticipate this strategy will provide insight into physiological vulnerabilities that become apparent upon antibiotic stress signal integration by pathogens, and the behavioral alterations mounted in response.
About the Speaker
Daniel Dwyer, Ph.D., is an Assistant Professor at the University of Maryland with appointments in the Department of Cell Biology & Molecular Genetics and the Institute for Physical Science & Technology, and is a member of the Maryland Pathogen Research Institute. Dr. Dwyer earned a B.S. in Biology (1999) from Boston College, and received research training during that time at the Dana-Farber Cancer Institute in the laboratory of Erik Flemington. He then worked for two years at Forticell Bioscience, a tissue engineering company, before graduate school. He earned his Ph.D. at Boston University in the Molecular Biology, Cell Biology and Biochemistry Program (2007) in the laboratory of James Collins of the Bioengineering Department. He has since served as an NSF Research Training Grant Post-doctoral fellow in the Department of Math & Statistics at Boston University, and as a Senior Scientist at the Center of Synthetic Biology at Boston University where he was co-mentored by James Collins and Graham Walker of the Biology Department at MIT. He has been a member of the UMD faculty since 2014.
