Introduction to EBICS Research
In a living system, cells perform their intended functions not individually, but collectively by forming three-dimensional structures to evolve over time. These structures are composed of clusters of cells, which may be thought of as biological machines, and they exhibit complex functional behaviors as they interact with each other and their environment through active or passive cell-cell and cell-matrix interactions. There has been extensive research focusing on behaviors of individual cells and the functions and properties of tissues and organs. Despite these efforts, little progress has been made to elucidate the complex functional behaviors of these biological machines, and the fundamental processes involved in such integration are poorly understood. We will develop novel experimental and computational tools that are essential for understanding and actively controlling cellular and cell network behaviors.
EBICS addresses the grand challenge of engineering multi-cellular biological machines that have desired functionalities and can perform prescribed tasks. These machines consist of sensing, information processing, actuation, protein expression, and transport elements that can be effectively combined to create functional units.
The broader scientific goals of EBICS are to establish a fundamental understanding of cell-cell and cell-environment interactions, and their control by biochemical and mechanical cues; to assemble and characterize the properties and performance of multi-cellular machines, and to thereby create the nascent discipline for building living, multi-cellular machines for a wide range of applications.
To build these complex machines we must understand how individual cells – neurons, myocytes, endothelial cells, and others – integrate their internal temporal developmental program with various environmental cues and with other cells to determine their differentiated states and biological behaviors. We must also understand the complex behaviors and functionalities that emerge from cell clusters composed of a single cell type, as well as clusters composed of multiple cell types. By understanding what mediates interactions between cells in nature, we can harness that knowledge to construct complex systems that can perform new tasks.
Pathways to a Biological Machine
EBICS has taken two fundamental approaches to developing biological machines. Using a classic engineering approach, we define the specifications for cellular machines with the desired capabilities, and develop the necessary parts (cells and cell clusters) and machine assembly pathways to construct such a machine. In parallel, we are using a systems biology approach to understand the emergent properties of cells and cell clusters to harness those properties to evolve interacting cell clusters that function within a biological machine with specific capabilities.