Embryonic Stem Cell Laboratory

Head of laboratory

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Overview of research program

The laboratory has ongoing interests in two distinct areas: Embryonic Stem Cells/Embryo Development and 3D Structure of Membrane Proteins.

Embryonic Stem Cells and Embryo Development
ES cells recapitulate many of the complex processes that occur during mammalian embryogenesis. This provides enormous experimental advantages because it is possible to identify molecules, signaling pathways, genetic and epigenetic events that contribute to stemness and that direct the differentiation of stem cells to specific cell fates.

We use ES cells to develop in vitro models of embryogenesis. The key features of the models include: (i) The capacity to examine pluripotence, directed differentiation and tissue patterning at the molecular level. (ii) The ability to ‘map’ the interrelated processes of cell signalling that control development, and manipulate those processes by chemical means. (iii) The development of tissue-culture protocols for the production of pure or highly enriched cell types, which can be tested in animal models of human disease and injury.

We use the information derived from our ES-cell models to test if similar mechanisms also drive the development of embryos themselves. This work has the potential to improve the viability of cultured IVF embryos.

3D Structure of Membrane Proteins
Membrane proteins are common and perform an enormous range of critical tasks in cells. However, it has continued to prove very difficult to obtain information on their 3D structures. Our research is directed towards developing computational tools that can be used to predict, refine, and compare the 3D structures of these proteins, with a focus on G protein-coupled receptors.

Selected publications

A.D. Conigrave, J.Y. Lee, L. van der Weyden, L. Jiang, P. Ward, V. Tasevski, B.M. Luttrell and M.B. Morris (1998) “Pharmacological profile of a novel cyclic AMP-linked P2 receptor on undifferentiated HL-60 leukemia cells”, Br. J. Pharmacol. 124 1580–1585

A.D. Conigrave, L. van der Weyden, L. Holt, L. Jiang, P. Wilson, R.I. Christopherson and M.B. Morris (2000) “Extracellular ATP suppresses proliferation and induces differentiation of human HL-60 leukemia cells by distinct mechanisms”, Biochem. Pharmacol. 60, 1585–1591.

L. van der Weyden, D.J. Adams, B.M. Luttrell, A.D. Conigrave and M.B. Morris (2000) “Pharmacological characterisation of the P2Y11 purinoceptor in haematological cell lines”,Mol. Cell. Biochem. 213, 75–81.

S. Dastmalchi, M.B. Morris and W.B. Church (2001) “Modelling of the structural features of integral-membrane proteins using REPIMPS (Reverse-Environment Prediction of Integral-Membrane Protein Structure)”, Protein Sci., 1529–1538.

P. Toonkool, D.G. Regan, P.W. Kuchel, M.B. Morris, and A.S. Weiss (2001) “Thermodynamic and hydrodynamic properties of human tropoelastin: Analytical ultracentrifuge and pulsed field-gradient spin-echo NMR studies”, J. Biol. Chem. 276, 28042–28050.

S. Dastmalchi, W.B. Church, M.B. Morris, T.P. Iismaa, J.P. and Mackay (2004) “Presence of transient helical segments in the sequence of galanin-like peptide (GALP) evident from 1H NMR, circular dichroism and prediction studies”, J. Struct. Biol. 146, 261–271.

M.B. Morris, J. Rathjen, R.A. Keough and P.D. Rathjen (2005) “Chapter 1: Biology of embryonic stem cells” in Human Embryonic Stem Cells (J.S. Odorico, R.A. Pederson and S.C. Zhang, eds) BIOS Scientific, USA, pp 1–28.

S. Dastmalchi, S. Beheshti, M.B. Morris and W.B. Church (2007) “Prediction of rotational orientation of transmembrane helical segments of integral membrane proteins using new environment-based propensities for amino acids derived from structural analyses”, FEBS J. 274, 2653¬–2670.

S. Dastmalchi, W.B. Church and M.B. Morris (2008) “Modelling the structures of G protein-coupled receptors aided by three-dimensional validation”, BMC Bioinformatics 9 (Suppl 1), S14.

M.B. Morris and W.B. Church (2009) “Invited review: Rhodopsin: Structure, function and oligomerisation”, Int. J. Biochem. Cell Biol. 41, 721–724.

Major collaborations

  • Prof. David Winkler (CSIRO, Melbourne) Systems biology of ES-cell differentiation
  • Dr Margot Day (University of Sydney) Cell signalling promoting embryo development
  • Dr Bret Church (University of Sydney) and Dr Siavoush Dastmalchi (Tabriz University, Iran) In silico tools for 3D modelling of membrane proteins