Multicellular Decision Making
How do cells coordinate their behaviors? Cells work together and make group decisions in systems ranging from bacterial biofilms to healing wounds to neuronal networks to cancer tumors. However, our understanding of how these collectives coordinate themselves is in its infancy when compared to what we know about how single cells function as individuals. This knowledge gap exists because of the technological challenges presented by connecting microscale events happening on a timescale of seconds inside cells to the macroscale events occurring over hours in collectives. Our lab addresses these challenges through creating and applying new methods to observe and control these behaviors. These new techniques enable us to develop a predictive understanding of how processes inside a single cell shape collectives, permitting us to synthetically engineer these group-wide behaviors for our benefit.
Tools we use and optimize include (but aren't limited to):
- genetically-encoded fluorescent biosensors
- widefield fluorescence microscopy
- darkfield microscopy
- confocal microscopy
- computational modeling
Collective Model Systems
We work with a wide range of model systems to help us in our long term goals of (1) identifying general principles biological systems implement to coordinate multicellular collectives and (2) synthetically controlling their behaviors.
Cellular Slime Mold
Dictyostelium discoideum, a cellular slime mold also known as the social amoeba, exists as a solitary amoeba when food is available. However, when they run out of food and starve, the amoebas begin to signal one another with waves of signaling molecules that form spirals and targets. As starvation continues, the cells begin chemotaxing toward the perceived center of these waves to aggregate together and form a multicellular fruiting body structure to be more easily transported to a new area with more food. Dictyostelium is a fantastic model system for studying cellular collective behavior because it is one of the few systems where we have the ability to simultaneously control collective signaling at the level of single cells and observe an entire collective and its signaling responses and behaviors simultaneously. To allow for this level of control, we have developed a toolbox of microfluidic, optical, and genetic tools. Working with these techniques we can address questions such as:
- What are the essential signaling dynamics for initiating and maintaining collective behavior?
- How do cells self-organize into patterns?
- How do cells specify their fates and exploit their individuality in collectives?
- How are individual genes responsible for modulating global pattern formation?
- How robust and reproducible are these collective behaviors?
- How can we re-program cellular collectives?
Tissue Gap Closure
Collective signaling and cell migration during wound healing allow us to explore how cells work together as a group to repair damage and navigate an unexpected situation. We are currently combining our expertise in visualizing signaling dynamics with model wound healing systems using fibroblast cells in extracellular matrix to answer questions such as:
- What signaling responses are responsible for wound healing?
- Which post-wound responses are chemically-driven and which responses are mechanically driven?
- Are there collective effects in 3D stromal tissue gap closure?
- Can we control and manipulate the wound healing response?
Bacterial biofilms offer us an opportunity to understand how different species can work together and exploit their native communication strategies to cooperate for the benefit of the collective. Many of the questions in biofilms are similar to those we ask in Dictyostelium, but require new techniques and approaches to answer. These include:
- How do bacteria synchronize themselves during biofilm formation?
- Can we change biofilm properties by changing synchronization?
Image Credits: Photos adapted from Höfer et al. Dictyostelium discoideum: Cellular Self-Organization in an Excitable Biological Medium (1995) and Owen Gilbert