Dr Tom Moore
Current research projects in Developmental Genetics
1. Pregnancy-specific Glycoproteins (PSG)
PSGs are part of the immunoglobulin (Ig) superfamily of proteins and are closely related to the widely-expressed and functionally diverse CEACAM protein family. Unlike CEACAMs, which are usually membrane-bound, PSGs are secreted by placental trophoblast (a fetal tissue) into the maternal circulation during pregnancy. Like many placental hormones, PSGs are encoded by a multigene family (10 genes in human: PSG1 – PSG9, PSG11; 17 genes in mouse: Psg16 – Psg32) and may have multiple roles in pregnancy including immunoregulation, thromboregulation and angiogenesis. PSGs have evolved independently in species with haemochorial placentation in which fetal trophoblast is in direct contact with maternal blood. In the human, PSGs may be the most abundant fetal proteins in maternal blood with reported levels >100 ug/ml. We are interested in the selective forces that drive the evolution of placental hormone multigene families. A possible explanation is the occurrence of escalatory arms races due to parent-offspring conflict (Haig, 1993), or, alternatively, individual PSG proteins may have different functions. We are working towards understanding these questions using individual PSG gene and protein sequence evolution, expression analysis, biochemical assays of PSG protein function, and gene targeting in the mouse.
Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions.
Moore, T. and G. S. Dveksler (2014).
Int J Dev Biol 58(2-4): 273-280.
DOI: 10.1387/ijdb.130329gd. (1,587kB).
Psg22 expression in mouse trophoblast giant cells is associated with gene inversion and co-expression of antisense long non-coding RNAs.
Williams, J. M., M. Ball, A. Ward and T. Moore (2015).
Reproduction 149(1): 125-137.
DOI: 10.1530/REP-14-0390.
2. PAR2-linked SPRY3 gene regulation and function
Sprouty proteins are regulators of cell growth and branching morphogenesis in a variety of developmental contexts and their deregulation is implicated in human disease. Unlike mouse Spry3, which is X-linked, human SPRY3 maps to the pseudoautosomal region 2 (PAR2) and is the nearest gene to the pseudoautosomal boundary. Unusually, the Y chromosome-linked copy of human SPRY3 is not expressed due to epigenetic silencing by an unknown mechanism. SPRY3 maps adjacent to X-linked TMLHE, which is highly expressed in cerebellar Purkinje cells. THLHE is a recently identified autism susceptibility gene and we have found that Spry3 also is highly expressed in cerebellar Purkinje cells and in other neural ganglion cells, and may be co-regulated with TMLHE in certain tissues. We are studying SPRY3 regulation and its role in development using human genetics, and molecular genetic and gene targeting techniques in the mouse.
3. Transgenics
As part of a multipartner infrastructural initiative funded by the Higher Education Authority, we are working in the context of the Irish Transgenic Network (www.transgenics.ie) to develop novel efficient methods of transgenesis in the mouse and rat using commercial (TARGATTTM) and customised (CRISPR) vectors combined with tissue electroporation. Progress on this work will be reported on the ITN website and here as it occurs.
