Dr Jelena Mann, Reader in Epigenetics
Dental Lecture Theatre E
Monday 25th January 2016
13.00 – 14.00pm
Dr Jelena Mann will present:
‘Epigenetic reprogramming of wound healing’
Adaptation to environmental insults is critical for ensuring fitness and survival of the species. Although long-term biological/genetic adjustment to insults exists (according to Darwinian theory), we recently discovered an alternative mechanism that provides epigenetic, heritable adaptation to an environmental insult within just 1 or 2 generations.
Liver fibrosis is a final common pathway of liver injury irrespective of aetiology. Using a model of liver injury, we show that predisposition to development of fibrosis exists and that presence of disease in previous generations alters such predisposition. Male offspring, from fathers or grandfathers that had liver injury, were protected from liver fibrosis and this adaptive response was amplified in the third generation such that the grade of disease was reduced from severe to mild. No changes in the degree of tissue injury or inflammation were observed between generations suggesting that adaptation was selectively directed at the fibrogenic/wound healing process.
The adaptation of wound healing response was also present in skin of females from the described model of transgenerational inheritance. The daughters and granddaughters of males that have had liver fibrosis had significantly diminished ability to close skin wounds, which was further evident in lower migration of skin fibroblasts in scratch-wound assays. These data show existence of transgenerational epigenetic transmission of wound healing properties and provides evidence of heritable mechanisms for the rapid adaptation of animals to environmental insults.
Finally, we have examined possible transmission mechanisms of the acquired characteristics in sperm of adapted animals to show that histone marks, DNA methylation and small non-coding RNAs may play a role.
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