MABEL FITZGERALD PRIZE LECTURE 2024: Structure to function - some stories from the cell surface

In my laboratory we combine x-ray crystallographic and cryoEM based analyses with biophysical and functional studies to study the assembly and modulation of cell surface signalling complexes involved in development and tissue homeostasis. We aim to generate mechanistic insights, at atomic resolution, which can be tested by functional studies in vitro and in vivo. Through interdisciplinary collaborations we have integrated mechanistic insight with functional context in fly, zebrafish and mouse model systems. I will discuss some of the recent results we have generated by applying this approach to the signalling mechanism of the semaphorin-plexin cell guidance system and to the extracellular modulation of signalling by the morphogen Wnt. Published examples of our work on these two systems include the following:

G.T. Powell=, A. Faro=, Y. Zhao=*, H. Stickney=, L. Novellasdemunt, P. Henriques, G. Gestri, E. Redhouse White, J. Ren, W. Lu, R.M. Young, T.A. Hawkins, F. Cavodeassi, Q. Schwarz, E. Dreosti, D.W. Raible, V.S.W. Li, G.J. Wright, E.Y. Jones*, S.W. Wilson*. (2024) ‘Cachd1 is a novel Frizzled- and LRP6-interacting protein required for neurons to acquire left-right asymmetric character.’ Science 384, 573-579.

V. Mehta, K.L. Pang, D. Rozbesky, K. Nather, A. Keen, D. Lachowski, Y. Kong, D. Karia, M. Ameismeier, J. Huang, Y. Fang, A. del Rio Hernandez, J.S. Reader, E.Y. Jones and E. Tzima*. (2020) ‘The Guidance Receptor Plexin D1 is a mechanosensor in endothelial cells.’ Nature 578, 290-295.

I.J. McGough=, L. Vecchia=, B. Bishop, T. Malinauskas, K. Beckett, D. Joshi, N. O’Reilly, C. Siebold, E.Y. Jones* and J-P. Vincent*. (2020) ‘Glypicans shield the Wnt lipid moiety to enable signalling at a distance.’ Nature 585, 85-90