Cells that help the body to defend itself against infection, such as leukocytes, are guided to the site of a wound or infection by chemical cues (a process known as chemotaxis) released by the affected tissue.  Metastatic cancer cells can also move out from the site of a primary tumor towards blood vessels by the same chemotactic process, resulting in the spread of cancer.  Both of these cell types move rapidly, using a specialized form of motility referred to as “amoeboid”.  This type of motility is characterized by extension of pseudopodia in the front of the cell, in the direction of movement, that is followed by contraction of the rear of the cell.  Amoeboid cells make specific contact with surrounding substrates, but they form weak, broad adhesions that allows them to rapidly break these contacts, enabling rapid movement.

The overall goal of the research in the Titus laboratory is to understand how the actin cytoskeleton and its associated motors, myosins, and actin binding proteins that link the cytoskeleton to adhesion receptors are used to generate amoeboid motility and how cells interpret extracellular cues to move directionally.  Our model organism of choice is the social amoebae Dictyostelium discoideum, a powerful experimental system that has a well-characterized actin cytoskeleton, a robust chemotactic response and is amenable to a wide range of experimental approaches, including molecular genetic, cell biological and biochemical methods.