Prof Robert Insall FRSE - Cell Migration and Chemotaxis


Insall head 038

Movement is a fundamental behaviour of cells and its regulation is particularly relevant to cancer because tumour invasion and metastasis are principal causes of death in cancer patients. Our group aims to understand how cell movement is regulated, using a mixture of genetics and microscopy. We are interested in several aspects of cell movement.

One is chemotaxis, in which external signals orient and attract cells, which is increasingly seen as a fundamental cause of metastasis. Metastasis, one of the most feared features of cancer, is caused when cells migrate out from a tumour into the blood, lymph or other tissues. Chemotaxis is clearly important in these processes but exactly how and why remain poorly understood.

Another is the regulation of actin polymerisation. Actin is the most abundant protein in eukaryotic cells. It polymerises into filaments that provide the mechanical force needed to push cells forwards. It also has a number of other biological roles. We are most interested in actin's roles in cell movement and vesicle sorting. In cell movement, the SCAR/WAVE complex, a large multiprotein assembly, promotes movement through the formation of large pseudopods. In vesicles, a related multiprotein complex based around WASH causes actin to polymerise on vesicles, where it mediates sorting of different components within the cell.

We study these two processes in a range of different cells, particularly Dictyostelium and melanoma cells. Dictyostelium is an amoeba in which the genetic analysis of movement is especially straightforward, and it has been the best experimental organism for studying chemotaxis. Melanoma is a very dangerous and highly metastatic cancer. Its metastasis is derived from the rapid migration of its cells through tissue. We have recently shown that this migration is underpinned by remarkably accurate chemotaxis.

When experimentally appropriate, we also examine human neutrophils, tumour-derived cells, cultured mammalian cells or other amoebas such as Entamoeba (the cause of amoebic dysentery) – anything that will help us to understand the conserved and fundamental mechanisms that drive cell movement.

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