The Laboratory of Developmental Genetics and Imprinting

The overall aim of our research is to elucidate key epigenetic and genetic mechanisms involved in gene regulation during mammalian development, from conception to birth to adulthood, and to examine the physiological action of these genes in specific systems.

Understanding how these developmental pathways are regulated and the consequences of their deregulation is providing valuable insight into human diseases and novel strategies for their management.

Genomic imprinting is a form of epigenetic regulation in mammals which results in the silencing of one copy of specific genes, according to parental origin. How this imprinting mechanism has evolved exclusively in mammals probably linked to the evolution of the placenta is being investigated by the SAVOIR consortium in collaboration with the Sanger Institute and the University of Melbourne (Kelsey, Reik). We are interested in understanding the epigenetic mechanisms of gene silencing that regulate imprinting, which range from DNA methylation to histone modifications, and from non-coding RNAs to higher order chromatin structure. How imprints are erased in early germ cells, and re-established when new gametes develop, is of special interest (Kelsey, Reik).

Imprinted genes have key roles in resource acquisition by mammalian organisms, affecting development and function of the placenta, growth of the fetus and infant, glucose and fat metabolism and thermogenesis after birth, as well as adult behaviours (Constancia, Kelsey). They and other epigenetically regulated genes are thus also potential targets for 'developmental programming' and lifelong metabolic adaptations of the organism; such adaptations can go wrong, and then perhaps result in diabetes and other common adult diseases (Constancia).

Epigenetic gene regulation plays general roles in development, particularly in the plasticity of embryonic stem cells, and the restriction of cell plasticity and potency during the establishment of organs. Reprogramming of epigenetic marks in germ cells and early embryos may be crucial for the generation of stem cells, and the identification of 'reprogramming factors' is thus valuable for regenerative medicine and novel cancer therapies (Hemberger, Reik).

Epigenetic factors interact with genetic factors in shaping the development of the early embryo and its placenta. Of special interest are proteases that appear to be involved in key differentiation pathways of the placenta (Hemberger), and morphogen gradients within the early embryo which lead to proper coordinated expression of Hox genes that establish the body axis of the mammalian fetus (Gaunt).

• Key publications from the laboratory
• Translating the Laboratory's Research into Action

Other Links

• The Epigenome
• Harwell Imprinting site
• SAVOIR
• CellCentric
• University of Melbourne