The Jones Group
The Invadosome and Migration Group (the Jones Group) carries out research that is directed to understanding the mechanisms of formation and turnover of podosomes and invadopodia in migrating leukocytes and tissue-invading metastatic cancer cells. We use a variety of optical microscopy techniques together with lentiviral-mediated delivery of XFP- tagged mutant cDNAs to examine the spatial and temporal interactions of key proteins involved in podosome and invadopodia dynamics as these cells move over and through matrix proteins.
Working with macrophages and dendritic cells, we found that the scaffolding protein WASP is essential for podosomes formation. Called WASP because of its association with Wiskott-Aldrich Syndrome (WAS), this protein had been reported to be the major actin-nucleating protein in white blood cells and platelets since it brings together free G-actin and the Arp2/3 complex when activated by the small GTPase, Cdc42. In contrast, invading carcinoma cell utilise the ubiquitous homologue of WASP, termed N-WASP, when making invadopodia.
Our group is a founder member of the Invadosome Consortium (www.invadosomes.org) with whom we share reagents and pre-publication information on the biology of these adhesion/migration/ invasion structures.
Boys with the lethal X-linked disorder WAS are lacking Wiskott-Aldrich Syndrome Protein (WASP) and fail to make adhesive podosomes in myeloid cells such as macrophages and dendritic cells (DC)