University of Dundee

Dr Alan Prescott

The role of the cytoskeleton in cell specific differentiation
Position: 
Senior Lecturer in Cell Biology
Address: 
College of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 384884, int ext 84884
Email: 

Research

Macropinocytosis by dendritic cells

Dendritic cells are essential for presentation of foreign antigens to T cells to illicit an immune response. They sample their peripheral tissue environment by engulfing large volumes of the surrounding mileu by macropinocytosis. Macropinosomes form from the aggregation of many actin-driven ruffles. This process is down regulated in mature dendritic cells which migrate to secondary lymphoid organs for antigen presentation to T cells. During the initial encounter with antigen there is a brief burst of enhanced macropinocytosis accompanied by a loss of podosomes-cell substrate adhesive structures that are also actin rich. The main thrust of our research is to understand how these two types of actin structures are regulated. Novel regulators of the actin cytoskeleton will be identified and localised by advanced microscopy techniques. (Collaborative project with Colin Watts)

Fig. A. Dendritic cell labelled for F-actin with phalloidin. Projection of a z-sFig. A. Dendritic cell labelled for F-actin with phalloidin. Projection of a z-series colour coded for depth. Membrane ruffles associated with macropinosome formation rise up from the surface of the cell (coloured green and blue). Podosomes associated with the base of the cell near the substrate are coloured orange.

Fig B/C. Scanning electron micrograph of a dendritic cell. C. Detail of B showing cell surface immuno-gold labelling (red) with MHC class I antibody.Fig B/C. Scanning electron micrograph of a dendritic cell. C. Detail of B showing cell surface immuno-gold labelling (red) with MHC class I antibody.

Fig D. Dendritic cells are the sentinels of the immune system, residing in peripFig D. Dendritic cells are the sentinels of the immune system, residing in peripheral tissues, constantly sampling their environment for invading pathogens. The image shows a 3D reconstruction of DCs in the sub-mucosal layers of the small intestine colour-coded for depth. On the left is the view from the front, on the right the rear view.

Teaching

BS31004: 4 lectures on Cell Shape and Movement.

BI4A01:  Module organiser, 6 Lectures on Cytoskeleton Function, Paper Analysis and Essay.

PhD student Techniques course: 1 lecture on Electron Microscopy Techniques.

Wellcome Trust/Dundee Cancer Centre Induction Programme: Introduction to Tissue Culture-lecture and demonstration. Microscopy course-lecture on Electron Microscopy, workstations on confocal microscopy.

DJ31001-Art, Science and Visual Thinking Module: Module co-organiser, Tutor coordinator and lecturer.

Publications

  1. Coleman, S.M., Prescott, A,R., Sleeman, J.E. (2014) Transcriptionally-correlated sub-cellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of Myotonic Dystrophy Type 1. Biochem J. 2013 Dec 20. [Epub ahead of print]
  2. Prescott, A.R., Bales, A., James, J., Trinkle-Mulcahy, L., Sleeman, J.E. (2014) Time-resolved quantitative proteomics implicates the core snRNP protein, SmB, together with the Survival of Motor Neuron protein, in neural trafficking. J Cell Sci. 2013 Dec 19. [Epub ahead of print]
  3. Banerjee, S., Buhrlage, S.J., Huang, H.T., Deng, X., Zhou, W., Wang, J., Traynor, R., Prescott, A.R., Alessi, D.R., Gray, N.S. (2014) Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1 tumour suppressor activated NUAK kinases. Biochem J. 1;457(1):215-25
  4. Sargent, F., Davidson, F.A., Kelly, C.L., Binny, R., Christodoulides, N., Gibson, D., Johansson, E., Kozyrska, K., Licandro Lado, L., Maccallum, J., Montague, R., Ortmann, B., Owen, R., Coulthurst, S.J., Dupuy, L., Prescott, A.R., Palmer, T. (2013) A synthetic system for expression of components of a bacterial microcompartment. Microbiology. 159(Pt 11):2427-36.
  5. Saunders,S.P., Goh, C.S., Brown, S.J., Palmer, C.N., Porter, R.M., Cole, C., Campbell, L.E., Gierlinski, M., Barton, G.J., Schneider, G., Balmain, A., Prescott, A.R., Weidinger, S., Baurecht, H., Kabesch, M., Gieger, C., Lee, Y.A., Tavendale, R., Mukhopadhyay, S., Turner S.W., Madhok, V.B., Sullivan, F.M., Relton, C., Burn, J., Meggitt, S., Smith, C.H., Allen, M.A., Barker, J.N., Reynolds, N.J., Cordell, H.J., Irvine, A.D., McLean, W.H., Sandilands, A., Fallon, P.G. (2013) Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects. Journal of Allergy and Clinical Immunology 2013 132(5):1121-9
  6. Groves, M.J., Johnson, C.E.,James, J., Prescott, A.R., Cunningham, J., Haydock, S., Pepper, C., Fegan, C., Pirrie, L; Westwood, N.J; Coates, P.J; Ganley, I.G; Tauro, S.(2013) p53 and cell cycle independent dysregulation of autophagy in chronic lymphocytic leukaemia. Br J Cancer. 109(9):2434-44
  7. Voss, M., Campbell, K., Saranzewa, N., Campbell, D.G., Hastie C.J., Peggie M.W., Martin-Granados C., Prescott A.R., Cohen PT. (2013) Protein phosphatase 4 is phosphorylated and inactivated by Cdk in response to spindle toxins and interacts with γ-tubulin. Cell Cycle. 12(17):2876-87
  8. Lek, H.S., Morrison, V.L., Conneely, M, Campbell, P.A., McGloin, D; Kliche, S., Watts, C., Prescott, A., Fagerholm, S.C. (2013) The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow. J Biol Chem. 288(21):14698-708
  9. Morrison, V.L., Macpherson, M., Savinko, T., Lek, H.S., Prescott, A., Fagerholm, S.C. (2013) The beta2 integrin-kindlin-3 interaction is essential for T cell homing but dispensable for T cell activation in vivo. Blood. 122(8):1428-36
  10. Elliott, J.L., Der Perng, M., Prescott, A.R., Jansen, K.A., Koenderink, G.H., Quinlan, R.A. (2013) The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability. Philos Trans R Soc Lond B Biol Sci. 368(1617):20120375
  11. Mackenzie, K.F., Clark, K., Naqvi, S., McGuire, V.A., Nöehren, G., Kristariyanto, Y., van den Bosch, M., Mudaliar, M., McCarthy, P.C., Pattison, M.J., Pedrioli, P.G., Barton, G.J., Toth, R., Prescott, A., Arthur, J.S. (2012) PGE2 Induces Macrophage IL-10 Production and a Regulatory-like Phenotype via a Protein Kinase A-SIK-CRTC3 Pathway. J Immunol. 190(2):565-77
  12. Hozhaj, G., Najafov, A., Toth, R., Campbell, D.G., Prescott, A.R., MacKintosh, C. (2012) ZNRF2 is released from membranes by growth factors and with ZNRF1 regulates the Na+/K+ATPase J. Cell Sci. 125, 4662-4675
  13. Martin-Granados, C., Prescott, A.R., Van Dessel, N., Van Eynde, A., Arocena, M., Klaska, I., Görnemann, J., Beullens, M., Bollen, M., Forrester, J.V, McCaig, C.D. (2012) A role for PP1/NIPP1 in steering migration of human cancer cells. PLoS ONE 7(7): e40769.
  14. Qu, B., Landsbury, A., Schönthaler, H.B., Dahm, R., Liu, Y., Clark, J.I., Prescott, A.R., Quinlan, R.A. (2012) Evolution of the vertebrate beaded filament protein, Bfsp2; comparing the in vitro assembly properties of a "tailed" zebrafish Bfsp2 to its "tailless" human orthologue. Exp Eye Res. 94(1):192-202
  15. Cameron, A.R., Wallace, K., Logie, L., Prescott, A.R., Unterman, T.G., Harthill, J., Rena, G. (2012) The antineurodegenerative agent clioquinol regulates the transcription factor FOXO1a. Biochem J. 443(1):57-64
  16. Logie, L., Harthill, J., Patel, K., Bacon, S., Hamilton, D.L., Macrae, K., McDougall, G., Wang, H.H., Xue, L, Jiang, H., Sakamoto, K., Prescott, A.R., Rena, G. (2012) Cellular Responses to the Metal-Binding Properties of Metformin. Diabetes. 61(6):1423-33