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
 Scientific Report 2010 Insall (116.44 kB)
Key PublicationsNeilson MP, Veltman DM, van Haastert PJ, Webb SD, Mackenzie JA, Insall RH (2011). Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour. PLoS Biol. 9, e1000618. Epub 2011 May 17.
Carnell M, Zech T, Calaminus SD, Ura S, Hagedorn M, Johnston SA, May RC, Soldati T, Machesky LM, Insall RH (2011). Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis. J Cell Biol. 193, 831-9. Epub 2011 May 23.
Muinonen-Martin AJ, Veltman DM, Kalna G, Insall RH (2010). An improved chamber for direct visualisation of chemotaxis. PLoS One. 5, e15309.
Veltman DM, Insall RH (2010). WASP family proteins: their evolution and its physiological implications. Mol Biol Cell. 21, 2880-93. Epub 2010 Jun 23.
Insall RH (2010). Understanding eukaryotic chemotaxis: a pseudopod-centred view. Nat Rev Mol Cell Biol. 11, 453-8. Epub 2010 May 6.
Insall RH, Machesky LM (2009). Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell. 17, 310-22.
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. Epub 2007 Jan 14.
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: Professor of Genetics and Cell Biology, University of Glasgow
2007-present: Group Leader, Beatson Institute for Cancer Research, Glasgow
2005-2007: Professor of Molecular Cell Biology, University of Birmingham
2003-2005: Reader in Molecular Cell Biology, University of Birmingham
2000-2010: MRC Senior Nonclinical Fellow (renewed 2005)
1999-2007: Group Leader, School of Biosciences, University of Birmingham
1995-1998: Group Leader, MRC Laboratory for Molecular Cell Biology, Cambridge & Lecturer, Department of Physiology, University College London
1995-1999: Wellcome Trust Career Development Fellow
1992-1995: Postdoctoral Fellow, Johns Hopkins Medical School, Baltimore, USA
1991-1992: Research Officer, MRC Laboratory of Molecular Biology, Cambridge
Committee membership
2012-present: MRC Advanced Course Masters Assessment Panel
2011-present: Deputy chair, MRC Nonclinical Fellowships Panel
2009-present: MRC Nonclinical Fellowships Panel
2004-2008: Chair, Cell Biology Theme Panel, Biochemical Society
Recent Publications
2011
Carnell M, Zech T, Calaminus SD, Ura S, Hagedorn M, Johnston SA, May RC, Soldati T, Machesky LM, Insall RH (2011). Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis. J Cell Biol. 193, 831-9.
King JS, Veltman DM, Insall RH. The induction of autophagy by mechanical stress. Autophagy 2011; 7: 1490-9
Neilson MP, Mackenzie JA, Webb SD, Insall RH. Modeling Cell Movement and Chemotaxis Using Pseudopod-Based Feedback. SIAM J Sci Comput 2011; 33, 1035-57
Neilson MP, Veltman DM, van Haastert PJ, Webb SD, Mackenzie JA, Insall RH (2011). Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour. PLoS Biol. 9, e1000618.
Veltman DM, Auciello G, Spence HJ, Machesky LM, Rappoport JZ, Insall RH (2011). Functional analysis of Dictyostelium IBARa reveals a conserved role of the I-BAR domain in endocytosis. Biochem J. 436, 45-52.
Itakura A, Verbout NG, Phillips KG, Insall RH, Gailani D, Tucker EI, Gruber A, McCarty OJ (2011). Activated factor XI inhibits chemotaxis of polymorphonuclear leukocytes. J Leukoc Biol. 2011 Aug 1. [Epub ahead of print].
Sapey E, Stockley JA, Greenwood H, Ahmad A, Bayley D, Lord JM, Insall RH, Stockley RA (2011). Behavioral and structural differences in migrating peripheral neutrophils from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 183, 1176-86.
Li A, Ma Y, Yu X, Mort RL, Lindsay CR, Stevenson D, Strathdee D, Insall RH, Chernoff J, Snapper SB, Jackson IJ, Larue L, Sansom OJ, Machesky LM. Rac1 Drives Melanoblast Organization during Mouse Development by Orchestrating Pseudopod- Driven Motility and Cell-Cycle Progression. Dev Cell 2011; 21: 722-34
Zech T, Calaminus SDJ, Caswell PT, Spence HJ, Carnell MJ, Insall RH, Norman JC, Machesky LM. The Arp2/3 activator WASH regulates alpha-5 beta-1 integrin mediated invasive migration. J Cell Sci doi: 10.1242/ jcs.080986, published online 23 Nov 2011
Davidson AJ, Insall RH (2011). Actin-based motility: WAVE regulatory complex structure reopens old SCARs. Curr Biol. 21, R66-8.
Insall RH (2011). Dogma bites back--the evidence for branched actin. Trends Cell Biol. 21, 2; author reply 4-5.
2010
King JS, Veltman DM, Georgiou M, Baum B,
Insall RH (2010).
SCAR/WAVE is activated at mitosis and drives
myosin-independent cytokinesis. J Cell Sci. 123,
2246-55.
Muinonen-Martin AJ, Veltman DM, Kalna G,
Insall RH (2010).
An Improved Chamber for Direct Visualisation of
Chemotaxis. PLoS ONE 5, e15309.
Neilson MP, Mackenzie JA, Webb SD, Insall RH (2010).
Use of the parameterised finite element method to
robustly and efficiently evolve the edge of a moving
cell. Integrative Biol. 2, 687-95.
Veltman DM, Insall RH (2010).
WASP family proteins - their evolution and its
physiological implications. Mol Biol Cell 21,
2880-93.
Carnell MH, Insall RH (2010).
Actin on disease - understanding the pathobiology
of cell motility with Dictyostelium discoideum. Sem
Cell Dev Biol. 22, 82-8.
Insall RH (2010).
Understanding eukaryotic chemotaxis: A
pseudopod-centred view. Nat Rev Mol Cell Biol. 11, 453-8.
2009
Pollitt AY, Insall RH (2009). Loss of Dictyostelium HSPC300 causes a scar-like phenotype and loss of SCAR protein. BMC Cell Biol. 10, 13.
Insall RH, Machesky LM (2009). Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell 17, 310-22.
King JS, Insall RH (2009). Chemotaxis: finding the way forward with Dictyostelium. Trends Cell Biol. 19, 523-30.
Pollitt AY, Insall RH (2009). WASP and SCAR/WAVE proteins: the drivers of actin assembly. J Cell Sci. 122, 2575-8.
2008
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.
2007
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.
Images
Lab Members
Post-docs: Jason King, Douwe Veltman
Scientific Officer: Peter Thomason
Clinical Research Fellow: Andy Muinonen-Martin (Wellcome Trust)
PhD Students: José Batista (FCT, Portuguese Government), Andrew Davidson, Laura Park
Visitor: David Knecht
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