Technical Lead – Robert Austin, Princeton University
This project couples the principles of evolutionary biology with techniques borrowed from nanotechnology in order to investigate the recurrence of resistance.
We find that bacteria exhibit all the fundamental phenomena that give rise to genomic instability and unregulated growth. In fact evolution in a bacterial system parallels mammalian evolution within cancerous tissue. By using a simple biological system such as E. coli bacteria, we can gain significant insight into the evolutionary adaption in tumor systems at the population level.
The Princeton PS-OC uses micro-fabrication techniques to create complex bacterial ecosystems with variable stress conditions in order to model cancer evolution and resistance.
Death Galaxy Experiments – Accelerated Evolution.
These experiments have been dubbed the “Death Galaxy” based on design principles. Galaxy refers to the structural design used - an interconnected array of micro-ecologies – similar to the stars comprising an astronomical galaxy. We use this galaxy of micro-ecologies to apply a spatially well-defined concentration gradient of the antibiotic ciprofloxacin (cipro). We monitor bacterial growth as a function of position inside the gradient, and we observe how quickly a subpopulation acquires the necessary mutations allowing it to thrive in the cipro-rich region. We intend to show how bacterial evolution resulting in resistance to Ciprofloxacin is accelerated by the physics' principles underlying this device.
Research on GASP mutant-wild-type dynamics
Cancer is characterized by uninhibited growth and invasion of healthy tissue. In these experiments, we culture two strains of E. coli bacteria in a micro-fabricated environment in order to model cancer. During starvation, the growth-advantage-in-stationary-phase (GASP) cells grow to a higher population than wild type cells. GASP cells also displace wild-type cells from nutrient-rich chambers. We mathematically model both the increase in GASP cell populations and the acceleration of their spatial invasion. Our experimental and model results corroborate recent caution against using tumor starvation as cancer therapy in spatially heterogeneous nutrient environments.
Micro-fluidic Channel Geometries: Asymmetric Barriers for Evolution
In these experiments, we study bacterial motion in asymmetric barrier arrays to understand how environments interact with cancer cells that express different levels of motility. We use silicon micro-structures with micro-fabricated channel geometries to influence the motion of bacteria. We show that bacterial motility can be rectified using asymmetric funnel-shaped structures. However, a large enough population of cells is able to “escape” an array of funnel barriers by collectively modifying their chemical micro-environment. This invasion-like behavior relates to metastatic cancer cells: cells that leave an initially confined environment to populate neighboring tissues. We extend the use of micro-structured devices to the study of cancer cell motility. These studies could provide critical keys to understanding the dynamics of tissue invasion and metastasis.