University of Dundee

Dr David Murray

Understand the basic molecular mechanics in the formation of subcellular structures
Position: 
Wellcome Trust and Royal Society Sir Henry Dale Fellow
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 381731, int ext 81731
Email: 

Research

Fundamentally different types of cells organize to form tissues. In each type of cell composing a tissue, specialized structures and organizations help to define their function. Our focus is to determine how cells develop the distinct structures that enable their specialization.

Processes such as cell polarization, migration, division, and ciliogenesis require the cell to remodel its cellular structures and are in part orchestrated by the polarity machinery. For example, reorganization of subcellular structures in epithelia is a critical aspect in normal development. In pathological conditions such as cancer, a remodeling of structures from polarity to migratory is necessary for metastasis, which leads inevitably to poor health prognoses. Other human genetic diseases such as ciliopathies are the direct result of malformation in the cilia subcellular structure. The properties of these processes are directly linked to polarization of the cell. Despite their importance, we cannot at the moment link molecular machineries to the cellular outcomes observed, which is critical to understanding their role human health and disease.

Remarkably, a common logistical machinery organizes the support for subcellular structures through delivery of their building blocks. Yet despite identification of the membranes, proteins, and pathways that make up this machinery, a basic understanding of their structural and molecular mechanics is lacking. Moreover, additional participants may be missing.

We harness membrane biophysical methods and state-of-the-art protein biochemistry, combined in synergy with experimental cell biology. This interdisciplinary approach is a powerful way to determine molecular function, and enables the research questions to lead our investigations.

Human health is critically dependent on the proper formation and maintenance of subcellular structures. Our long-term aim is to bridge scales from the molecular machinery involved to the consequences at a tissue level. We lead our investigations in the context of cellular signaling that is critical to human health, such as that of cancer and transitional states of tissue development.

Publications

1. Murray, D.H.*, Jahnel, M.*, Lauer, J., Avellaneda, M.J., Brouilly, N., Cezanne, A., Morales-Navarrete, H., Perini, E., Ferguson, C., Lupas, A.N., Kalaidzidis, Y., Parton,R.G., Grill, S., and M. Zerial. An endosomal tether undergoes an entropic collapse to bring vesicles together. Nature 2016 537, 107-111 *, equal contribution.

2. Murray, D.H., and L.K. Tamm. Molecular Mechanism for Phosphatidylinositol-4,5-bisphosphate-Syntaxin Interaction. Biochemistry 2011 50(42), 9014-9022.

3. Murray, D.H., and L.K. Tamm. Clustering of Syntaxin-1A in Model Membranes is Modulated by

Phosphatidylinositol-4,5-bisphosphate and Cholesterol. Biochemistry 2009 48(21), 4617-4625.

4. Murray, D.H., Tamm, L.K., and V. Kiessling. Supported Double Membranes, J. Struct. Biol. 2009 168 (1), 183-189.

5. Kiessling, V., Domanska, M.K., Murray, D., Wan, C., and Tamm, L.K. Supported Lipid Bilayers: Development and Applications. Volume 4, pp 411-422 in Chemical Biology. Wiley Encyclopedia of Chemical Biology. 2009. John Wiley & Sons, Hoboken.

6. Kim, M., Xu, Q., Murray, D., and D.S. Cafiso. Solutes Alter the Conformation of the Ligand Binding Loops in Outer Membrane Trans-porters. Biochemistry 2008 47 (2), 670-679