Working Groups

Symmetry Breaking (WG1)

Objective: 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 initial symmetry breaking.

Hypothesis: Coincident differentiation of divergent cell phenotypes with appropriate spatial control is required to achieve functional organoids.

Group Leader(s)

Organoid Formation (WG2)

Objective: 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.

Hypothesis: Coincident differentiation of divergent cell phenotypes with appropriate spatial control is required to achieve functional organoids.

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.

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.

Motile Bots (WG6)

Objective: Develop motile machines involving differentiated and trained neurons, muscle, and vasculature. The machines will have sensing and actuation abilities with elementary logic. They can be stimulated by light or electric fields, chemical gradients, or they can be self-propelled. Performance improvement or optimization can be achieved through training or adaptation.

Hypothesis: Such semi-intelligent machines will emerge through cell-cell and cell-scaffold interactions under the guidance of specific chemical, mechanical, and electrical cues. 

Group Leader(s)

Pump Bots (WG7)

Objective: Develop pumping and filtration biomachinery involving differentiated and trained neurons, muscle, and vasculature. The machines will have abilities to transfer biologically relevant fluids through synthetic conduit or blood vessels and further remove impurities in a spontaneous or external stimuli-responsive manner.

Hypothesis: Such machines will emerge through cell-cell and cell-matrix interactions under the guidance of specific chemical, mechanical, and electrical cues.

Group Leader(s)