Welcome to the Belardi Lab at the University of Texas at Austin!
We are a young, passionate group of interdisciplinary researchers combining expertise in molecular engineering, synthetic biology, chemical biology, and biophysics to better diagnose and treat disease.
Our lab seeks to probe, perturb, and re-program biological barriers across length scales. Metazoans - which include humans - have evolved to assemble exquisite semi-permeable membrane structures that regulate the flux of select material in and between cells and tissues. The complex, multi-component topologies and mesh-like architectures of biological barriers are rich sources of biological information and often deteriorate in pathological conditions. With molecular tools in hand, we study epithelial cells and tissue, extracellular matrix, and cell membrane interfaces to gain a quantitative and mechanistic understanding of these barriers. Leveraging our fundamental insights, researchers in the lab build smarter molecules, materials, and cells for improving drug bioavailability in the gut and brain, detecting and repairing cancerous tissue, and for regenerative medicine applications.
Compared to the cellular proteome, extracellular matrix (ECM) proteins harbor unique and surprising forms of post-translational modifications. These modifications reflect tissue state and are often remodeled during disease progression, e.g. tumorigenesis and fibrosis. How do these modifications affect ECM self-assembly and potentiate cell signaling? And how might they be used as a next-generation biomaterial? Our approach to these questions is to synthesize and characterize modified forms of ECM. In parallel, we pursue creative methods for detecting ECM modifications in patient samples as a new diagnostic platform.
Extracellular Matrix
Modifications
Epithelial Contacts & Engineering
Spatially separated junctions line epithelial cell membranes and are instrumental in governing tissue homeostasis and cohesion. In vertebrates, the task of regulating paracellular permeability falls on the apical-most junction, the tight junction. We work on uncovering how tight junctions form, how they are maintained over time, and how they respond to biological insults. These efforts are coupled with the design of reagents and materials to manipulate tight junctions for improving drug bioavailability and for treating transport disorders.
Cell-based therapies and grafts have transformed the medical industry, yet suffer from serious side-effects and drawbacks. Synthetic cells – cell-like assemblies built from defined molecular parts – offer an attractive alternative to overcome many of the issues associated with engineered patient cells. Our lab combines protein engineering, ligation chemistry and microfluidics to construct synthetic cells that perform advanced operations, such as adhesion and sensing, for therapeutic and regenerative medicine applications.
Synthetic Cell Construction
Protein Switches
Protein function is intimately linked to molecular conformation. The ability to trigger changes in protein conformation through external, orthogonal inputs point to a future of control over biological activity and function. Under development in our lab are molecular switches that augment membrane and cytoskeletal organization in cells with user-defined inputs. We envision a cascade of effects following activation that extend from single molecules to cells and tissue. In doing so, macroscopic parameters – tissue adhesion, stiffness, and permeability – can be toggled through protein-based switches.
NEWS
2021-present
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