Research Fellows Directory
Dr Jason King
University of Sheffield
We are interested in the process of macropinocytosis, a mechanism by which cells can reach out, and engulf large volumes of their surrounding fluid. Cells need to ingest their environment for many reasons. The most fundamental is to feed, providing nutrients to sustain growth, but in multicellular organisms it is also critical for immune cells to continuously sample their environment, and watch out for foreign bodies. Taking in large quantities of extracellular fluid is however not without its risks, and many harmful viruses and bacteria can also exploit macropinocytosis as a way to enter host cells.
Despite their important roles in both normal cell behaviour and disease, surprisingly little is known about what happens to macropinosomes inside the cell. After the macropinosome has formed, the cell is left with a large bag of extracellular liquid (with whatever it contains) enclosed by a membrane. The cell then has the challenge of breaking this into smaller vesicles and concentrating the contents so the macropinosome can integrate with other cellular compartments such as the digestive machinery and recover any nutrients.
Another problem the cell faces is that the membrane bounding the macropinosome comes from the cell surface, and therefore contains all the surface proteins that come with it. To prevent these from being eaten along with the macropinosome contents, and to maintain enough of these proteins at the surface for the cell to function, it is crucial to rescue these proteins and shuttle them back.
The need to remodel vesicles and remove selective proteins from their surface is not unique to macropinocytosis. We want to understand the basic, fundamental principles by which cells manipulate vesicles. We therefore hope to ultimately extend our work to other cellular pathways such as the engulfment of bacteria and the capture and digestion of damaged intracellular components.