Abstract: Chemotaxis – directing cells using gradients of diffusible molecules - is a central part of normal biology, for example embryogenesis. It also underpins many diseases, for example cancer metastasis.

Most chemotaxis studies think of chemotactic gradients as passive things, so the cells’ job is just reading cues that are imposed from outside. We are more interested in self-generated gradients, in which cells create their own gradients at the same time as migrating up them. This means they creating their own steering cues. We find that self-generated gradients establish information-rich scenarios that are fun, counterintuitive and require detailed mathematical and computational modelling to understand. They give exceptionally satisfying results, however. In particular, they allow cells to detect features of the environment at a distance and thus to solve complex mazes.

We find self-generated gradients in a growing range of cell types; I will introduce a few.

We have recently found a remarkable extension - some self-generated gradients repel cells rather than attracting them. Two gradients that are each attractive on their own can repel cells when mixed together. This has led us to study interactions between multiple chemoattractants detected by the same receptors. Such competition is universal in, for example, immune cell signalling, but rarely considered.

Taken together, self generated gradients allow cells to use simple rules to create complex and unexpected patterns of migration, just like those seen in biology.

Suggested reference:

Tweedy, L., Thomason, P.A., Paschke, P.I., Martin, K., Machesky, L.M., Zagnoni, M. and Insall, R.H., 2020. Seeing around corners: Cells solve mazes and respond at a distance using attractant breakdown. Science, 369(6507), p.eaay9792.

Biography:

PhD: LMB, Cambridge (studying development in Dictyostelium with Rob Kay)

Postdoc: Johns Hopkins Medical School, Baltimore, USA (moving to chemotaxis with Peter Devreotes)

MRC Fellow: UCL (studying Ras proteins and chemotaxis)

Professor: University of Birmingham (studying the control of the Arp2/3 complex and starting to talk with mathematicians, including some fine ones at Warwick)

Senior PI: Beatson Institute, Glasgow (chemotaxis in cancer cells). Got more interested in maths & computers, so moved to:

Professor: University of Glasgow, Institute of Cancer Sciences