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Erica D Watson

Lecturer in Reproductive Biology, Tel: +44 (0)1223 333807, Email: edw23@cam.ac.uk

Research summary
It is known that maternal folate deficiency during pregnancy is associated with neural tube defects, placental abnormalities and intrauterine growth restriction. However, little is understood about how folate functions during development. Folate metabolism is necessary to transfer methyl-groups destined for downstream targets including DNA. Therefore, folate may play a key role in epigenetic modifications of DNA affecting gene expression.

My research explores the epigenetic effects of abnormal folate metabolism on placental and fetal development. To study this, I use a genetic mouse model containing a mutation in a key enzyme in the folate cycle. This mutation results in congenital malformations similar to those seen during human maternal folate deficiency. Interestingly, the effects of this mutation are multigenerational. Due to the sizable number of imprinted genes expressed in the placenta, trophoblast cell differentiation and function may be particularly at risk during abnormal folate conditions. Using these mice along with various genetic, cellular and molecular techniques, my specific research aims are to:

1) Explore the developmental and functional consequences of abnormal folate metabolism in trophoblast cells.

2) Determine the global DNA methylation status in mutant trophoblast cells, and subsequently assess specific effects on gene regulation.

3) Establish whether the embryonic phenotypes that result from this mutation are caused by abnormal trophoblast function.

Key publications

Padmanabhan et al, 2013. Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell, 155(1): 81-93.

Cherukad J, Wainwright V and Watson ED. (2012) Spatial and temporal expression of folate transporters and metabolic enzymes in the developing mouse placenta. Placenta 33(5): 440-8

Watson ED Hughes M, Simmons DG, Natale DR, Sutherland AE and Cross JC. (2011) Cell-cell adhesion defects in Mrj mutant trophoblast cells are associated with failure to pattern the chorion during early placental development. Developmental Dynamics, 240(11): 2505-19. [Associated image selected for cover of Developmental Dynamics 241(4), 2012]

Watson ED, Mattar P, Schuurmans C and Cross JC. (2009) Neural stem cell self-renewal requires the Mrj co-chaperone. Developmental Dynamics 238(10): 2564-74.

Watson ED, Geary-Joo C, Hughes M and Cross JC. (2007) The Mrj co-chaperone mediates keratin turnover and prevents the formation of toxic inclusion bodies in trophoblast cells of the placenta. Development 134(9): 1809-17. [Image selected for issue cover]

Elmore CL, Wu X, LeClerc D, Watson ED, Bottiglieri T, Krupenko N, Krupenko S, Cross JC, Rozen R, Gravel RA and Matthews RG. (2007) Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Molecular Genetics and Metabolism 90(5): 85-97. [Image selected for issue cover]

Watson ED and Cross JC. (2005) Development of structures and transport functions in the mouse placenta. Physiology 20(3): 180-93.

Contributor to Under the Microscope, a collection of videos that show glimpses of the natural and man-made world in stunning close-up. View the development of a mouse embryo.

Funding: Next Generation Fellowship, CTR; Natural Sciences and Engineering Research Counsel of Canada (NSERC); Canadian Institutes of Health Research (CIHR).