Introduction to EBICS Research
Cells perform their intended functions not individually but collectively by forming temporally evolving, three-dimensional structures comprised of clusters of cells, and through active or passive cell-cell and cell-matrix interactions. Despite extensive research focusing on behaviors of individual cells and the functions and properties of tissues and organs, little progress has been made to elucidate the complex functional behaviors of interacting cell clusters, or biological machines. While there is general recognition that cellular behaviors are guided by integrated biological, biochemical, and physical (geometrical, mechanical, electrical, thermal) cues, 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.
Model of a biological machine showing sensing, information processing, actuation and transport.
EBICS will address 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; assemble and characterize the properties and performance of multi-cellular machines, and thereby create the nascent discipline for building living, multi-cellular machines for a wide range of applications.
Initially, EBICS has focused on building two biological machines: BetaCell Factory, an implantable cellular machine for glucose sensing and insulin release for the treatment of diabetes; and BioBot, an autonomous cellular machine for detecting and neutralizing toxins in the environment. To build these complex machines we must understand how individual cells – neurons, myocytes, endothelial cells, and beta cells – 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 homotypic cell clusters composed of a single cell type and heterotypic cell clusters composed of multiple cell types. By understanding the factors, signals, forces, and external micro environments that mediate interactions between cells in nature, we can harness that knowledge to construct complex neuro-muscular systems coupled to artificial endothelial vessels that can perform multimodal logical operations in functional biological machines.
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.
Integration of EBICS Research Thrusts
The BetaCell Factory and BioBots Thrusts constitute the major machine efforts within the EBICS research program. The design specifications of these biological machines will be defined within the CellClusters and SourceCells Thrusts, which will develop unique and reusable machine components. Within the Thrusts the Center has defined the vertical dependencies (grey arrows) between groups working to generate various desired cells and cell clusters, as defined by design specifications, to build the biological machines. Research in emergent behaviors will permeate all research initiatives contributing to the building of biological machines and a fundamental unserstnding of basic biological development.