Working Groups

Symmetry Breaking (WG1)

The Symmetry Breaking Working Group was established in 2015 to focus on the initial mechanisms within multicellular systems that lead to the emergence of complex structures and patterns. The goals of this Working Group are to: 1) identify and control the extrinsic and intrinsic parameters governing the initiation of emergent behaviors of multicellular systems, and 2) examine the spatiotemporal dynamics of emergent behaviors that arise from asymmetric patterning events that occur at the very earliest stages of cell differentiation and self-organization.The majority of our working group’s efforts have focused on examining these properties in human pluripotent stem cells. This past year, we have further identified the molecular mechanisms of local inter- and intracellular interactions that result in larger-scale emergent behaviors of multicellular systems, including biomolecular, biophysical and bioelectrical properties. We have focused primarily on examining the initiation and propagation of asymmetric properties within thecontext of “organoids” created from pluripotent stem cell sources that constitute the basis ofseveral ongoing EBICS research projects throughout the various Working Groups.

Group Leader(s)

Organoid Formation (WG2)

The goals of the working group are to explore and model the formation of organoids in vitro and the formation of functional structures in natural systems and to direct the co-differentiation of pluripotent stem cells to achieve controlled spatial patterning of multicellular constructs by harnessing biochemical, bioelectrical, and biophysical cues with a focus on subsequent steps towards organoid formation. The work includes studies with engineered cells and extracellular matrices and studies of developmental dynamics.

 

Group Leader(s)

Neural Circuits (WG3)

To build biological machines composed of cellular and molecular components that dynamically interact to coordinate larger system functions, it is important to understand the characteristics of the cells and their components and how they behave upon differentiation. Thus, we will determine in real time, using enabling technologies (reporter genes, matrices etc.), how stem cells and progenitor cells exposed to intrinsic and extrinsic cues behave and interact in a coordinated fashion. In addition, we will develop methods to predict and control phenotypic changes in differentiating cells in order to meet the machine’s specifications. A unique aspect of this project is the use of emerging technologies and computational tools to understand, in real time, and eventually predict the complex nature of cell functions of differentiating cells in a defined and controlled microenvironment.

Initially, we will address how individual cells integrate their internal temporal developmental program with various environmental cues and from other cells to determine their differentiated states and biological emergent behaviors. We are using optical imaging to capture the emergent behaviors of gene and proteins expression and mass movement in earliest cell type neuroepithelial cells to specified motor neurons. We will examine how the intrinsic and extrinsic factors interact in a systematic way to provide the necessary guidance cues during cell differentiation, neural function and synapse formation. Our long-term goal for this project is to instructively guide and manipulate the functional outputs of a complex cellular machine. We will explore and translate how these cells will collectively perform their intended functions by addressing cellular activity in temporally evolving active integrated populations of cells. For example, an ability to adjust function based on feedback sensing of the microenvironment will improve the capabilities and nutrient supply within the machine.

Group Leader(s)

Neuron-Muscle (WG4)

The overall goal of the neuromuscular junction (NMJ) group is to understand developmental process of NMJ and further recreate the NMJ that meets the stimulus-responsive actuation/movement of our various biological machines. In order to accomplish our goal, the NMJ group has been seeking to establish (1) a protocol for differentiation of pluripotent embryonic stem cells (ESCs) and neural progenitor cells to motor neuron cells, (2) a synthetic extracellular matrix that supports NMJ formation on muscle sheet, (3) a protocol for co-culture of motor neuron cells and myoblasts, (4) a microfluidic device that can control spatial organization of NMJ, and (5) a label-free imaging tool to analyze NMJ. The group also aim to understand emergent behavior underlying NMJ formation and function by interrogating the roles of spatial organization and direct interaction of motor neurons and skeletal myoblasts towards NMJ formation. Additionally, the group is identifying additional design parameters to improve the quality of NMJs through genetic modification of motor neuron cells with optically sensitive channelrhodopsin and computational modeling.

Group Leader(s)

Vascularization (WG5)

The goal of the Microvascular Networks research is to design and construct functional microvascular networks for use in the next generation of biological machines. 

These networks must be large enough to require a circulation in order to meet the metabolic needs of the other cell types. Currently, differentiated cell lines are being used in microfluidic devices to create networks that span a distance of up to 1 mm and can be perfused from side channels. Mouse ES cells and mouse and human MSCs are also being developed that could be used both for the endothelial network and for the pericytes and smooth muscle cells presumably needed for long-term viability and phenotypic stability.

Group Leader(s)

Motile Bots (WG6)

The goals of the Motile Bots working group are to design, construct, and analyze a family of biobots that emerge from interactions between cells and elementary engineered scaffolds. Their objective functions are walking and swimming in fluids. The cells involved are muscle, neurons and endothelial cells. These motile bots will ultimately have intelligence, as the neurons will stimulate the muscle cells on an on-demand basis by sensing the environment. Another goal is to use the biobot platforms to study emergent properties of neuron cell clusters, cross talk between neurons and muscle, and neuromuscular junctions.

Group Leader(s)

Pump Bots (WG7)

The goals of the Pump Bots working group is to design and construct biological machinery with pumping functionality as a testbed for studying emergent behaviors of single and multiple cell types, and to use the biological pumps to improve the sustainability of cell clusters and other biological machinery of interest. 

Group Leader(s)