Imagine discovering a 60-piece jigsaw puzzle tossed out onto a table, with each puzzle piece oriented in no particular order, some facing up and some down. If I asked you to guess the complete image the puzzle is depicting from these randomly sprawled pieces, you would probably have a hard time. This predicament is analogous to where the field of epithelial tight junction biology is at the moment. We know there are many individual molecular pieces (proteins) that assemble in unique ways to form a larger macromolecular puzzle (tight junction), but we cannot guess what the complete puzzle image might look like. The problem is made more challenging because it is a three-dimensional (3D) puzzle and we do not actually know the 3D shapes of most pieces, making it impossible to solve. The way these oddly shaped single molecules interlock and amass to form a complete multi-molecular tight junction is critical for understanding many fundamental biological processes in humans. Piece by piece, we plan on putting together the tight junction 3D puzzle.

Color Image of Genome
Figure 1

The Vecchio Laboratory addresses fundamental yet unresolved questions in endo- and epithelial tight junction biology. Disruptions to tight junctions in various tissues are hallmark of human diseases including Alzheimer’s, Parkinson’s, multiple sclerosis, hepatitis and other hepatic diseases, inflammatory bowel disease, stroke, renal wasting, nutrient malabsorption, food poisoning, vision disorders, deafness, and cancer. To understand the mechanisms of tight junction form and function, detailed investigations into their intermolecular interactions are required. Utilizing techniques across the interdisciplinary fields of cell and molecular biology, biochemistry, biophysics, and structural biology, our research aims for mechanistic insight into structure−function relationships between proteins localized at tight junctions. This work is vital for clarifying the roles these proteins play in human disease, for defining the molecular bases that underlie epithelial tissue specialization, and for the development of novel therapeutics aimed at ameliorating tight junction-related diseases

Protein molecules
Figure 2

We make our home in the Department of Biochemistry, on the City Campus of the University of Nebraska—Lincoln. The Department of Biochemistry has 29 faculty with strengths in metabolism, biofuels, lipid biosynthesis, membrane protein biochemistry, molecular mechanisms of disease, and redox biology; and focuses on a plethora of living systems from prokaryotes to plants, parasites, pests, and people.

Research Image
Figure 3