The human body is assembled from modular parts with sizes ranging from organs to atoms. These parts are also organized hierarchically, each constructed from ever-smaller building blocks that contribute to the higher order functional properties of our bodies.
In the Gartner lab, we are working to organize the body’s building blocks into defined structures spanning the subcellular to tissue length scales. Through our efforts, we hope to gain a deeper understanding of fundamental biological processes relating to the establishment of tissue structure and its breakdown during disease.
Programmed Assembly of 3D Tissues
Using a chemical approach, we are synthesizing microtissues composed of multiple cell types and with programmed connectivity from the bottom-up. We functionalize cells with short oligonucleotides to impart specific adhesive properties. Hybridization of complementary DNA sequences between neighboring cells enables the assembly of multicellular structures with defined cell-cell contacts. The kinetic parameters of the assembly process depend on DNA sequence complexity, density, and total cell concentration. Thus, cell assembly can be highly controlled, allowing the design of microtissues with defined cell composition and stoichiometry.
Our current efforts aim to extend the synthetic capabilities of Programmed Assembly with the goal of building "structure-function" relationships for individual tissues. For example, we are working to program the assembly of the human mammary gland from purified cellular components in vitro. We are using the assembled structures as models to study how different cells interact within structurally defined tissues, and how these interactions might breakdown during the early stages of breast cancer.
Subcellular organization of cell-cell interactions
Signaling complexes involved in intercellular communication are often found at the interfaces between cells. As a consequence, their activities are influenced by the architecture of the cell and surrounding tissue. We are developing strategies to control and visualize the mechanistic steps of receptor activation that may be influenced by cell and tissue structure. We will look for signatures of long-range receptor organization at cell-cell and cell-surface interfaces using these strategies.
Novel therapeutics and probes
We are also exploring the potential of recently developed chemical tools to provide new applications for currently approved small molecule and protein-based drugs.