Germ Cell Development and Epigenetics Research Group
Research Group Head
Epigenetic modifications to the chromatin (DNA plus the proteins that package it) provide a long-term “directory” or “memory” of which genes should be switched on or off in each cell, and thereby underpin cell identity and organ function. Conversely, disrupted epigenetic states occur in diseases including cancer, metabolic and behavioural disorders.
Importantly, epigenetic modifications are reversible in normal cells, allowing gene activity to be changed when necessary. This occurs most extensively in developing germ cells in which epigenetic information is re-set to equip the sperm and oocyte with the appropriate epigenetic information for directing embryonic and post-natal development in the offspring.
However, epigenetic programming is susceptible to alteration by environmental influences such as chemicals, diet and drugs. Significantly, altered epigenetic states can also be transmitted to the next generation and may affect health and development in the offspring. Such changes may contribute to the developmental origins of health and disease (DOHaD) in a parent’s offspring.
The Germ Cell Development and Epigenetics group aims to improve understanding of epigenetics in the germ cells and the effects of epigenetic change on the offspring. Specifically, we use gene mutations and drugs to disrupt epigenetic modifier function in mouse germ cells to determine:
(i) the function of specific epigenetic modifiers in germ cell development, and
(ii) the ability of germ cells with altered epigenetic states to direct development in the parent’s offspring.
We also employ ex-vivo gonad culture and in-vivo mouse genetic models to examine the function of signalling pathways on epigenetics and gonad and germ cell development, providing insights into the formation of testis cancers and infertility.
By exploring germ-line development and the establishment and function of epigenetic information in the germ line, our research will contribute to understanding human disease, including various cancers and the development of novel drugs targeting epigenetic processes.
- Germ Cell Differentiation and Testis Cancer
- Reproductive Epigenetics
- Testicular Germ Cell Tumours (TGCTs)
Stringer J, Barrand S and Western PS 2013 Fine-tuning evolution: germ-line epigenetics and inheritanceReproduction 146(1):R37-48. doi: 10.1530/REP-12-0526.
Miles DC, Wakeling SI, van den Bergen JA, Stringer J, Wilhelm D, Sinclair AH and Western PS(2013). Signaling through the TGF beta-Activin receptors ALK4/5/7 regulates testis formation and male germ cell development. PLoS One 8(1):e54606. doi: 10.1371.
Miles DC, van den Bergen JA, Wakeling SI, Anderson RD, Sinclair AH andWestern PS (2012) The proto-oncogene Ret is required for fetal germ cell survival. Developmental Biology 365(1):101-109.
Western PS, van den Bergen JA, Miles DC, and Sinclair AH (2010) Male fetal germ cell differentiation involves complex repression of the regulatory network controlling pluripotency. The FASEBJ. 24:3026-3035.
Western PS, Miles DC, van den Bergen JA, Burton M, Sinclair AH. (2008) Dynamic regulation of mitotic arrest in fetal male germ cells. Stem Cells. 26: 339-347.