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Moore group

Developmental Genetics research group overview

Our research focuses on the genetic control of embryonic development during pregnancy.  Three strands of research aim to investigate:

1. The evolution and mechanisms of action of the pregnancy-specific glycoproteins during pregnancy, and their therapeutic potential.
2. The regulation and function of the imprinted human pseudoautosomal region-2 (PAR2) gene SPRY3.    
3. The development of new methods for making transgenic mice using TARGATT^TM and CRISPR technologies.

The methods that we use include: mouse molecular genetics and transgenics, trophoblast stem cells, tissue electroporation, fluorescence microscopy, recombinant protein production, chromatin immunoprecipitation, DNA genotyping, pyrosequencing, DNA methylation analysis, biochemical assays, immunohistochemistry, and other techniques as required.

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.

Figure 1: Structures of mouse (PSG16 – PSG32) and human (PSG1 – PSG9, PSG11) PSG proteins. (Adapted from McLellan et al., 2005, and http://www.carcinoembryonic-antigen.de/index.html). Red color-coded ‘N’ domains are Ig variable-like domains, and blue ‘A’ and ‘B’ domains are Ig constant-like domains. Black ‘lollipops’ indicate potential N-linked glycosylation sites. Note that atypical amino and carboxy terminal sequences are also color-coded.

 

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. 

People in the Developmental Genetics research group

Current group members

Melanie Ball

Dr Zhenfei Ning

Dr John Williams

 

Past group members

Dr Kathy Barriscale-Walsh

Dr Evelyn Matthews

Dr Andrew McLellan

Dr Ronan O’Riordan                                                       

Dr Daniel Shanley                                                                            

Dr Rosalie Waldron                                                       

Dr Freda Wynne

Publications

Dr Tom Moore research publications to April 2017

Dr Tom Moore Research Publications to April 2017

 

Dr Tom Moore UCC Research profile

Dr Tom Moore UCC Research profile.

 

Selected Publications 2008 - 2014‌

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.

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)

Pregnancy-specific glycoproteins bind integrin αIIbβ3 and inhibit the platelet-fibrinogen interaction.

Shanley, D. K., P. A. Kiely, K. Golla, S. Allen, K. Martin, R. T. O'Riordan, M. Ball, J. D. Aplin, B. B. Singer, N. Caplice, N. Moran and T. Moore (2013).
PLoS One 8(2): e57491.
DOI: 10.1371/journal.pone.0057491. (2,534kB)

Maternal-fetal resource allocation: co-operation and conflict.

Fowden, A. L. and T. Moore (2012).
Placenta 33 Suppl 2: e11-15.
DOI: 10.1016/j.placenta.2012.05.002. (254kB)

Expression of pleiotrophin and its receptors in human placenta suggests roles in trophoblast life cycle and angiogenesis.

Ball, M., M. Carmody, F. Wynne, P. Dockery, A. Aigner, I. Cameron, J. Higgins, S. D. Smith, J. D. Aplin and T. Moore (2009).
Placenta 30(7): 649-653.
DOI: 10.1016/j.placenta.2009.05.001. (686kB)