Research Synopsis

We are interested in biological movement at the cellular level; current projects in the lab are addressing fundamental questions about how cytoskeletal dynamics are regulated to allow cells to divide, crawl, and change their shape. Our primary model systems are cultured Drosophila cell lines. Fruit fly cells are well-suited for our research for several reasons:

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First, the use of cultured cells allows us to visualize cytoskeletal dynamics with high spatial and temporal resolution using light microscopy. For example, S2 cells - our workhorse cell line - is a macrophage-like cell type that typically grows in culture with a spherical shape that makes visualization of the cytoskeleton challenging. When plated on glass coverslips coated with the lectin concanavalin A, S2 cells attach and spread out on the substrate. Spread cells also reorganize their actin network to build a lamellipodium and orient their microtubules in a radial array that allows clear microscopic resolution. In addition, it is fairly straightforward to engineer stable cell lines that express fluorescent proteins for time-lapse imaging of dynamic cellular processes (see movie).

Second, Drosophila cells are highly susceptible to gene inhibition by RNAi. Most of the cell lines we work with have a high affinity uptake system for dsRNAs and it is possible to generate loss-of-function phenotypes by simply adding dsRNA to the target genes to the culture medium. With the development of genome-scale dsRNA libraries and high-throughput instrumentation over the last several years, Drosophila cells have been transformed into a powerful tool for gene discovery.

Third, the use of Drosophila as a model system allows us to adopt a multi-tiered approach to understanding the cytoskeleton. In addition to studying biological activity at the level of the individual cell, we can take advantage of traditional genetic approaches to study gene function in the whole organism throughout development.

Students and postdocs in the lab will be trained in a variety of techniques including microscopy, biochemistry, and high-throughput cell-based screening while pursuing projects centered on understanding cellular organization, behavior, and dynamics.