The ability of cells to move in response to external signals is one of the most remarkable features of life. One form of fast cellular migration is referred to as “amoeboid” and it is characterized by extension of pseudopodia, or sometimes blebs, from the front of the cell in the direction of movement, followed by contraction of the rear of the cell. A number of different cells use this type of speedy migration mechanism, including cells of the immune system that are guided to the site of a wound or infection by chemical cues secreted by the affected tissue (a process known as chemotaxis). Additionally, the metastatic spread of cancer cells can also occur by cells moving in an amoeboid fashion from the site of a primary tumor towards blood vessels by the same chemotactic process.
The goal of Titus laboratory is to understand the mechanism of directed amoeboid movement. The work focuses on three aspects: 1) how the actin cytoskeleton and its associated motors, myosins, are used to generate amoeboid motility; 2) how cells interpret extracellular cues to move directionally; 3) how amoeboid cells adhere to their surrounding substrates using broadly distributed, yet weak adhesions that enable rapid movement. The model organism of choice for these studies is the social amoebae Dictyostelium discoideum (Dicty), a powerful experimental system that has a well-characterized actin cytoskeleton, a robust chemotactic response, and is amenable to molecular genetic, cell biological, and biochemical method approaches. There is a high degree of functional and molecular conservation between Dicty and mammalian cells so use of this model system also enables studies of the evolution of molecular motors and cytoskeleton proteins.
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