Dr MICHAEL WILLIAMS
Lecturer
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Personal Details
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Biography
Education: Ph.D., Molecular Genetics, University of Notre Dame, Notre Dame, Indiana, 46556, USA. 1999.
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Research Interests
In 1982 it was discovered that mutated forms of the small GTPase Ras were present in human cancers. This discovery led to intense research in an attempt to dissect Ras function and towards the development of Ras inhibitors for cancer treatment. Given their pivotal role in normal and developmentally regulated processes, it is not surprising that Ras-like small GTP-binding proteins are involved in an amazing variety of pathological human conditions including oncogenesis, inflammation, and infection .
Similar to Ras, aberrant activation of Rho-family GTPases in cancers is now well documented. Because of these reasons, the small GTPase field is an intensive area of research. In the last 20 years most research focussed on identifying proteins, yet the function of each member of these families remains unclear. Questions such as specificity towards their targets in vivo and spatiotemporal regulation remain to be solved. The challenge of today's researcher is to understand the function and the regulation of this multifunctional family of cellular regulators in physiological conditions as well as to unravel their contribution to pathological processes and thus find attractive targets to develop novel therapeutic strategies.
There are several reasons for studying Drosophila cellular immunity as a method for understanding Rho-family GTPase regulation and function in vivo.
1. Many genes, including Rho GTPases, involved in regulating haematopoiesis and cellular immunity have been maintained across taxonomic groups ranging from flies to humans.
2. Many aspects of Drosophila and mammalian innate immunity appear to be conserved.
3. Drosophila has a simplified genetic system with little redundancy, and well established genetic tools available for this study.
Haemocytes bled from third-instar larvae, migrating on extracellular matrix.(Christopher Sampson)
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Current Research
The function of Rho GTPases in the Drosophila cellular immune response: Given their pivotal role in normal and developmentally regulated processes, it is not surprising that small GTP-binding proteins are involved in an amazing variety of pathological human conditions including oncogenesis, inflammation, and infection. Thus, the small GTPase field is an intensive area of research. The requirement and activity of Rho GTPases differs depending on their environment. In vivo 3D models are absolutely required to finally understand the physiological function of Rho GTPases and their regulators. A main advantage of using the fly as a model organism is the ease with which the effects of altered gene expression can be phenotypically analysed and thus the functions of different gene products deduced. In our lab we use an organismal model to understand Rho GTPase regulated processes during teh larval immune reposne and embryonic macrophage migration. This approach should provide biologically relevant functions under physiological conditions to unravel Rho-family GTPase contributions to pathological processes and thus find attractive targets to develop novel therapeutic strategies
LAB MEMBERS
PhD Students
Keliya Bai How is the RhoGEF Ephexin regulated biochemically and genetically during the Drosophila anti-parasitoid cellular immune response?
Laurynas Pliuskys Epigenetic control of Drosophila haematopoiesis
Christopher Sampson How does the Dock-type RhoGEF Zizimin-related regulate the Drosophila anti-parasitoid immune response?
Other Current Lab Members
Laura Howell
Honours students
Lianne Fraser
Lee McCaig
Miguel Xavier
Craig Young
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Collaborations
External
Dr. Marie-Odile Favarque, iRTSV/LTS ; UMR873 INSERM, CEA-Grenoble, France: Phagocytosis and adhesion in Drosophila cellular immunity.
Dr. Arno Müller, Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee, UK: Phagocytosis and adhesion in Drosophila cellular immunity.
Dr. Klemens Rottner, Cytoskeleton Dynamics Group, Helmholtz Centre for Infection Research (HZI) Inhoffen Strasse, 7 D-38124 Braunschweig, Germany: Cell migration of Drosophila larval circulating immunosurveillanc cells
Internal
Drs Colin Selman and John Speakman: Involvement of Rho-family GTPases in aging.
Dr. Mirela Delibegovic: The role of the Drosophila PTP1B homolog, PTP61F, in the cellular immune response.
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Research Grants
Research Grant
Current Research Grants
Royal Society Research Grant 2008-2009
CLSM Project Grant 2009-2010
Former Research Grants
Swedish Research Council Collaboration Grant 2006-2007
Postdoctoral Research Fellow with Medical and Odontological Faculty, Umeć University, 2001-2003
Swedish Research Council (VR) Postdoctoral fellow, 1999-2001
Other Grants
Swedish Cancer Foundation Congress Grant 2007
Swedish Cancer foundation of Northern Sweden Congress Grant 2007
Umeć University Congress Grant 2007
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Meetings Organized
Organized the 1st European Small GTPase Conference, Umeć, Sweden (August 29-31, 2007) Sponsored by the Cancer Research foundation of Northern Sweden and the Swedish Cancer Research Foundation.
Co-organizing the 2nd European Small GTPase Conference, Aussois, France (June 17-21, 2009)Sponsored by the Conference Jacques Monod.
Co-organizing the 1st Scottish Fly Meeting, Edinburgh, Scotland (December 11, 2009).
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Editorial Board
Editor-in-Chief of Small GTPases: from basic principle to disease
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Selected Publications
#Invited review
Sampson CJ, Fauvarque MO and Williams MJ (2010) The Drosophila RhoGEF Zizimin-related is necessary for a proper cellular immune response. In preparation
Williams MJ (2009) Rac1 and Hsp83 regulate beta-integrin endosomal recycling in Drosophila cellular immunity. In preparation
Howell L, Sampson CJ and Williams MJ (2010) A directed screen for genes involved in the Drosophila anti-parasitoid immune response. In preparation
#Sampson CJ and Williams MJ (2010) Rho-family GTPases: What can we learn from Drosophila? In preparation for Small GTPases.
#Fauvarque MO and Williams MJ (2010) Cell signalling in adhesion and migration: lessons from Drosophila immunosurveillance. In preparation for the Journal of Cell Science.
Williams MJ (2009) The c-src homologue Src64B activates the Drosophila cellular immune response. Journal of Innate Immunity 1:335-339. Link to J. Innate Immunity
Williams MJ (2009) The Drosophila cell adhesion molecule Neuroglian regulates Lissencephaly-1 localisation in circulating immunosurveillance cells. BMC Immunology 10:17. Link to Pubmed
Bergeret E, Perrin J, Williams M, Grunwald D, Thevenon D, Taillebourg E, Bruckert F, Cosson P and Fauvarque MO (2008) TM9sf4 function in cell adhesion and phagocytosis is required for Drosophila cellular immunity. Journal of Cell Science 121: 3325-3334. Link To Pubmed
The Tribolium Genome Sequencing Consortium (There are 51 authors, including MJ Williams) (2008) The first sequence of a beetle, Tribolium castaneum, a model for insect development and pest biology. Nature 452: 949-955. Link to Pubmed
Zou Z, Evans J, Lu Z, Zhao P, Sumathipala N, Williams MJ, Hultmark D, Hetru C, and Jiang H (2007) Innate immunity genes in Tribolium castaneum. Genome Biology8:R177. Link to Pubmed
#Williams MJ (2007) Drosophila Hemopoiesis and Cellular Immunity. Journal of Immunology 178: 4711-4715. Link to Pubmed
Williams MJ, Habayeb MS, and Hultmark D. (2007) Reciprocal regulation of Rac1 and Rho1 in Drosophila circulating immune surveillance cells. Journal of Cell Science 120: 502-511. Link to Pubmed
Williams MJ, Wiklund M-L, Wikman, S, and Hultmark D. (2006) Rac1 signaling in the Drosophila larval cellular immune response. Journal of Cell Science 119: 2015-2024. Link to Pubmed
Williams MJ, Ando I and Hultmark D. (2005) Drosophila melanogaster Rac2 is necessary for a proper cellular immune response. Genes to Cells 10: 813-823. Link to Pubmed
Zettervall C, Anderl I, Williams MJ, Eva Kurucz, Ruth Palmer, Istvan Ando and Dan Hultmark. (2004) A directed screen for genes involved in the activation of Drosophila hemocytes. PNAS 101: 14192-14197. Link to Pubmed
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