BME 280B Seminar: Dr. Jeff Hasty – “Engineered cellular differentiation in physiologically relevant environments”
Welcome to the 6th week of our BME 280B seminar series, a weekly seminar covering topics of current research in computational biology and bioinformatics.
Open to all, food is provided. Class enrollment is not required.
Please join us this week to learn more about the works of Dr. Jeff Hasty:
Title of Talk: Engineered cellular differentiation in physiologically relevant environments
Presenter: Dr. Jeff Hasty, Professor of Bioengineering and Molecular Biology and Director of the Synthetic Biology Institute, University of California, San Diego
Description: The original defining approach to synthetic biology is the use of mathematical models to design and construct gene circuits. This engineering approach has guided our recent work on the synchronized lysis circuit (SLC), a quorum-sensing program that drives a bacterial population to grow, lyse, and release a payload in cycles, turning tumor-colonizing bacteria into a self-dosing bioreactor. In two-dimensional culture the SLC cycles with a period near 5 hr, while in animals that period is roughly 24 hr. I will first describe a measurement platform we built to ascertain how the physiological environment changes circuit behavior.The device has two layers and permits tuning of oxygen levels, matrix composition, gradients, and co-culture independently at tissue scale while imaging single colonies. I will then describe a general design theme that focuses on plasmid replication as opposed to transcription. If two plasmids in a cell share one origin(dupORI), a single controller limits both, so one gains copies only as the other loses them. A simple model captures this: the total copy number settles to a fixed value, but the split between the two plasmid types is free to drift, and cell division and the noise in replication spread a clonal population across a range of plasmid configurations. With environmental pressure, a single strain tunes the relative abundance of plasmid types to maximize growth, and this principle can be used to engineer differentiation within a clonal population. I will close with two designs we are currently testing. In the first, the two plasmids of a dupORI pair cut each other, with colicin selection holding the balance, so the strain can switch between discrete states and retain them as a type of read/write circuit. In the second, one strain runs two separate lysis circuits that take turns, delivering two payloads sequentially.
Bio: Jeff Hasty received his Ph.D. in physics from the Georgia Institute of Technology in 1997, where he learned how to do science from his advisor Kurt Wiesenfeld. He was subsequently a postdoctoral fellow at Boston University, where he learned engineering from Jim Collins (’98– ’01). Somewhere during his postdoctoral stay with Jim he mutated from a theoretical physicist into a hybrid computational/molecular biologist. He is currently at the University of California, San Diego, where he holds the Paul A. Libby Endowed Chair and is a Professor in the Departments of Bioengineering and Molecular Biology, and Director of the Synthetic Biology Institute. Cells, constructs, and microfluidic devices from his lab are in use for research and teaching around the world and he is known for freely sharing genetic constructs and measurement technologies that “just work.”
Hosted by: Professor of Applied Mathematics, Dr. Marcella M. Gomez