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Project 6
Nanopatterned Surfaces for Quantitative Analysis
of Tumor Cell Signaling & Migration
R.L. Juliano, Ph.D., Professor of Pharmacology, Project PI
Project 6 will be coordinated by the C-CCNE PI, Dr. Juliano, who is known for his work on integrins and their role in signal transduction. However, it relies on the exciting and innovative nanotechnologies developed by two young investigators: Muhammed Yousaf of the UNC Chemistry Department and John Muth of the NC State Electrical Engineering Department. Important roles will be played by Dr, Klaus Hahn (UNC Pharmacology) through his unique capabilities for dynamic imaging of intracellular signaling, and Dr. James Bear (UNC Cell & Developmental Biology) with great expertise in cytoskeletal function and live cell imaging. This Project falls under the rubric of “Research Enablers” since it addresses fundamental issues in cancer cell biology rather than a translational research problem.
This project will be based on the ability of the Yousaf and Muth laboratories to create novel nanopatterned surfaces with precise spatial and temporal control of geometry and chemical composition. In the Yousaf technology nano-regions can be derivatized with ligands that can bind integrins, cadherins or other receptors, leaving the remainder of the surface passive. Thus cell protrusions will be able to bind to some regions of the surface but not others. In some cases the adhesive ligands will be provided by the Combinatorial Library Core. The nanopatterning is dynamically controlled during experiments, and the surfaces are optically tractable, thus allowing various forms of microscopy. This is an ideal system to quantitatively study the complex kinetic and topographic relationships between cell-matrix interactions, signaling, cytoskeletal function, and tumor cell migration. In the Muth technology an electronically controlled optically active surface is created that allows nano-sized regions to be selectively illuminated to generate fluorescence signals or to be subjected to photochemical manipulations.
Goals of Project 6 include:
- Nanofabrication and testing of the novel chemically and optically active nanopatterned surfaces by the Yousaf and Muth laboratories.
- Exploration of the relationships between the spatial distribution, density and affinity of immobilized adhesive ligands and tumor cell adhesion, spreading, and migration as observed via live cell imaging. The nanopatterning technology will also be linked to the superb functional biosensor technology developed in the Hahn lab. This will address the quantitative relationships between engagement of cell surface adhesion receptors, and signaling via Rho GTPase and MAP Kinase pathways, as they relate to tumor cell migration.
This Project will make extensive use of the Combinatorial Library Core to generate specific ligands for integrins and biosensors for study of the signaling pathways. This basic research-oriented project seeks to further develop nanopatterning technology to understand tumor cell signaling and migration phenomena at new levels of precision and quantitation.
Links:
Professor Juliano's homepage
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