Head of laboratory

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1. Regulation of early embryo development
The programme undertakes fundamental investigation of the regulation of normal development of the embryo from the time of fertilization until after the embryo has implanted into the mother’s uterus. This is the period of greatest loss of viability in the human life-span. The research programme investigates the process of cell division, differentiation and cell survival during this period of development. An important aspect of the study is to understand how environmental stresses perturb these processes in the early embryo and the molecular mechanisms involved. Of particular interest are the consequences of stresses imposed by forms of assisted reproductive technologies, such as IVF, on the long-term viability and homeostatic stability of resulting progeny.

2. Developmental Epigenetics
Underlying the normal processes of development are a complex and dynamic changes in the pattern of gene expression in the embryo. Many of these critical changes involve processes of epigenetic modification of the genome. Epigenetic modifications are mitotically heritable but do not cause a change in the DNA sequence. Changes to the epigenetic status of cells are considered to be the primary basis for cellular differentiation during development. The lab is investigating: the biochemical basis for epigenetic reprogramming in the early embryo and during oncogenic transformation; the changes to chromatin proteins during differentiation to defined cell lineages; and the regulation of gene expression during the onset of first transcription from the embryo’s new genome.

3. Formation of stem cells
The formation of stem cell lineages by the early embryo requires the expression of a core set of pluripotency genes. Their expression is auto-regulatory, such that perturbation of one can adversely effect the expression of all. The maintenance of the expression of these genes is the key to the regenerative capacity of stem cells. This project investigates at the cellular and molecular level the regulation of these pluripotency genes. The project also investigates how cellular stresses can adversely effect their expression and hence the pluripotentially of the stem cell lines.

Major funding sources

  • ARC

Selected publications

Lu DP, Chandrakanthan V, Cahana A, Ishii S, O'Neill C. (2004) Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development. Journal of Cell Science. 117(Pt 8):1567-76.

Chami O, Evans G, O'Neill C. (2004) Components of a platelet-activating factor-signaling loop are assembled in the ovine endometrium late in the estrous cycle. American Journal of Physiology: Endocrinology and Metabolism. 287(2):E233-40.

Li A, Chandrakanthan V, Chami O, O’Neill C (2007) Culture of Zygotes Increases p53 Expression in B6 Mouse Embryos which Reduces Embryo Viability. Biology of Reproduction 76, 362–367

Li, Y, Day, MI, O’Neill C (2007) Autocrine activation of ion currents in the two-cell mouse embryo, Experimental Cell Research.313: 2786-2794.

Li Y, Chandrakanthan V, Day MI, O’Neill C (2007) Direct Evidence for the Action of Phosphatidylinositol (3,4,5)-Trisphosphate-Mediated. Biology of Reproduction. 77: 813-821.

Mahsoudi B, Li A, O’Neill C. (2007) Assessment of the long-term and transgenerational consequences of perturbing preimplantation embryo development Biology of Reproduction. 77: 889-896

Jin XL, O’Neill C (2007) CREB expression and regulation in the mouse preimplantation embryo. Reproduction 134: 667-675
O'Neill C. (2008) Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development. Reproduction 136 147-156

Morgan HD, Jin XL, Li A, Whitelaw E, O’Neill C (2008) The Culture of Zygotes to the Blastocyst Stage Changes the Post-Natal Expression of an Epigenetically Labile Allele, Agouti Viable Yellow, in Mice. Biology of Reproduction 79, 618–623

Jin XL, Chandrakanthan V, Morgan HD, O’Neill C (2008) Preimplantation embryo development requires the latency of TRP53 expression induced by a ligand-activated PI3 kinase/AKT/MDM2 mediated signaling pathway. Biology of Reproduction 80: 286-294