While addressing specific molecules for our biological studies, we have produced generally applicable approaches to visualize and control signaling. These include new fluorescent biosensor designs to quantify conformational changes of endogenous proteins, and to visualize the conformational changes of individual molecules in living cells. This work includes the development of bright dyes that report protein conformational changes. We are developing engineered domains that can be inserted into target proteins to control protein function using either light or small molecules. Other new methods selectively activate specific protein interactions. We benefit greatly from collaborations with other labs who focus on computational image analysis, modeling of signaling dynamics, and developing novel microscopes.
In our biological projects, we are inducing macrophages to engage geometrically regular objects, while controlling protein activity at precise times and positions. Using multiplexed imaging, we simultaneously control and visualize signaling in this sytem. This enables us to model lines of force and molecular interactions governing target recognition and sheds light on feedback control of GTPase networks. In metastatic cells we are asking how GTPases are regulated by multiple GEFs, GDIs, and GAPs with overlapping roles, and how this is affected by the tumor microenvironment.
Check here for ongoing projects
See the "tools" page for information regarding new microscopy and molecular imaging approaches (biosensors, optogenetics, engineered small molecule responses, dyes, image analysis and modeling…).
For their support over the years, we are grateful to the National Institutes of Health, National Science Foundation, American Cancer Society, American Heart Association, Leukemia and Lymphoma Society, Arthritis Foundation, Human Frontiers in Science Program, Department of Defense, NC Biotechnology Center, Deutsche Forschungsgemeinschaft, Autism Speaks, UNC's University Cancer Research Fund, UNC Lineberger Cancer Center, and the UNC Institute for Developmental Disabilities.
~ Updated 04/14/2021