1. Engineering novel bacterial two component sensors
Two component signal transduction systems are the primary means by which bacteria sense and respond to stimuli in the environment. Tens of thousands of two component systems have been identified in the genomic and metagenomic sequencing databases, but very few have been characterized. We are developing novel high throughput strategies for identifying the chemical and physical input signals recognized by two component systems, and harnessing them for applications in basic science, medicine and industry.
2. Optogenetic method development
Optogenetics is a technology whereby different molecular biological processes inside living organisms can be precisely perturbed using light and genetically encoded light-switchable proteins. We are developing mathematical models that predict how optogenetic tools respond to different light inputs to program gene expression dynamics, proteolysis, and other processes with unprecedented accuracy and precision. We are also harnessing new light-switchable phytochrome-family proteins from plants, cyanobacteria and other organisms in order to study and control the processes of the cell with unprecedented resolution.
3. Using light to characterize gene circuit dynamics
Over the first 14 or so years of synthetic biology, researchers have programmed cellular behaviors using a wide range of analog and digital genetic circuits. However, the vast majority of these circuits are only characterized at the steady state (a single time point). We know that evolution has produced gene circuits that respond in a highly dynamical fashion to changing or even constant input signals. We are developing an optogenetic framework for rigorously characterizing the dynamics of gene circuits. This work is already resulting in improved mathematical models of gene circuit performance, and will allow more advanced biological behaviors to be engineered.
4. Development of hardware for high-throughput characterization of genetic devices
A major limitation in our ability to engineer biology is that we often have limited knowledge of how genetic devices perform in the environment of the cell. The major problem is that we lack the "wetware" and hardware tools to systematically and rigorously characterize the devices. We are engineering custom light input/light output hardware and combining it with our optogenetic tools to characterize genetic devices in a wide range of contexts with unprecedented accuracy, precision, and throughput.
5. Engineering multicellular behaviors
Many of the wondrous feats accomplished by biological systems, such as the growth or regeneration of tissues, requires that cells communicate with one another. Moreover, theory tells us that we can engineer dramatically more complex behaviors given an increasing number of non-overlapping communication channels. We are engineering new chemical and physical channels of cell-cell communication in order to program advanced multicellular behaviors, including tissue growth.