Introduction
 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 two aspects of cell movement.
The first is chemotaxis, in which external signals orient and attract cells, which is increasingly seen as a fundamental cause of metastasis.
The second is the SCAR/WAVE complex, an assembly of proteins that promotes movement through the formation of large pseudopods. We study these two processes in a range of different cells, particularly Dictyostelium, in which the genetic analysis of movement is especially straightforward.
Cell movement is a central part of biology, from conception to death. Embryos form their complexity and shape from the movement of layers of cells as well as the migration of individual cells through tissues. While, adult wound healing and responses to infection require skin and immune cells to migrate to where they are needed.
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, the connection between chemical signals outside the cell and movement, is important in these processes but remains very poorly understood.
We are trying to understand cell movement – what drives it and most importantly how it is steered. Most mammalian cells use pseudopods made of polymerised actin to power migration. Our current research focuses on the proteins and pathways that control these pseudopods.
We mostly use Dictyostelium, taking advantage of its excellent genetics, and prominent cell movement and 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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Lab Report
 Link to Insall Scientific Report 2008 121.78 Kb
Key PublicationsHeath RJ, Insall RH (2008). Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles. J Cell Sci. 121, 1054-64.
Pollitt AY, Insall RH (2008). Abi mutants in Dictyostelium reveal specific roles for the SCAR/WAVE complex in cytokinesis. Curr Biol. 18, 203-10.
Andrew N, Insall RH (2007). Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nat Cell Biol. 9, 193-200.
Ibarra N, Blagg SL, Vazquez F, Insall RH (2006). Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways. Curr Biol. 16, 717-22.
Zaki M, Andrew N, Insall RH (2006). Entamoeba histolytica cell movement: a central role for self-generated chemokines and chemorepellents. Proc Natl Acad Sci USA 103, 18751-6.
Biography
Education and qualifications
1989: PhD, MRC Laboratory of Molecular Biology, Cambridge, Supervisor Rob Kay
1986: BA (Hons), Natural Sciences, University of Cambridge
Appointments
2007-present: Group Leader, Beatson Institute for Cancer Research, Glasgow
2005-2007: Professor of Molecular Cell Biology, University of Birmingham
1999-2007: Senior Fellow, School of Biosciences, University of Birmingham
1995-1998: Group Leader, MRC Laboratory for Molecular Cell Biology, Cambridge & Lecturer, Department of Physiology, University College London
1992-1995: Postdoctoral Fellow, Johns Hopkins Medical School, Baltimore, USA
1991-1992: Research Officer, MRC Laboratory of Molecular Biology, Cambridge
Committee membership
2004-2008: Chair, Cell Biology Theme Panel, Biochemical Society
Recent Publications
Heath RJ, Insall RH (2008). Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles. J Cell Sci. 121, 1054-64.
Heath RJ, Insall RH (2008). F-BAR domains: multifunctional regulators of membrane curvature. J Cell Sci. 121, 1951-4.
King JS, Insall RH (2008). Chemotaxis: TorC before you Akt. Current Biol. 18, R864-6.
Pollitt AY, Insall RH (2008). Abi mutants in Dictyostelium reveal specific roles for the SCAR/WAVE complex in cytokinesis. Curr Biol. 18, 203-10.
Andrew N, Insall RH (2007). Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nat Cell Biol. 9, 193-200.
Calaminus SD, McCarty OJ, Auger JM, Pearce AC, Insall RH, Watson SP, Machesky LM (2007). A major role for Scar/WAVE-1 downstream of GPVI in platelets. J Thrombosis and Haemostasis 5, 535-41.
Insall R, Andrew N (2007). Chemotaxis in Dictyostelium: how to walk straight using parallel pathways. Current Opinion in Microbiol. 10, 578-81.
Kae H, Kortholt A, Rehmann H, Insall RH, Van Haastert PJ, Spiegelman GB, Weeks G (2007). Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras pathways using specific RasGEFs. EMBO Reports 8, 477-82.
Zaki M, King J, Futterer K, Insall RH (2007). Replacement of the essential Dictyostelium Arp2 gene by its Entamoeba homologue using parasexual genetics. BioMed Central Genetics 8, 28.
Ibarra N, Blagg SL, Vazquez F, Insall RH (2006). Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways. Curr Biol. 16, 717-22.
Insall RH, Jones GE (2006). Moving matters: signals and mechanisms in directed cell migration. Nat Cell Biol. 8, 776-9.
King J, Insall RH (2006). Parasexual Genetics Using Axenic Cells. In “Dictyostelium discoideum Protocols”, eds L. Eichinger & F. Rivero, Methods in Molecular Biology 346.
Pollitt AY, Blagg SL, Ibarra N, Insall RH (2006). Cell motility and SCAR localisation in vegetatively growing Dictyostelium cells. Eur J Cell Biol. 85, 1091-98.Somesh BP, Vlahou G, Iijima M, Insall RH, Devreotes PN, Rivero F (2006). RacG regulates morphology, phagocytosis, and chemotaxis. Eukaryot Cell 5, 1648-63.
Zaki M, Andrew N, Insall RH (2006). Entamoeba histolytica cell movement: a central role for self-generated chemokines and chemorepellents. Proc Natl Acad Sci USA 103, 18751-6.
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