Diet induced stress and epigenetic control of circadian clock regulation
Internship Description
Workshop Description
The majority of our
physiological and metabolic processes are coordinated by an internal clock,
which has evolved as an adaptive response to the daily light-dark cycles. Thus,
several physiological and behavioral activities display an oscillatory rhythmic
period of 24 hours. This highly conserved molecular mechanism is achieved
through a specific program of gene expression, characterized by a complex
interaction between clock-core proteins, chromatin remodelers and epigenetic
events associated with the oscillatory nature of circadian transcriptional
activity in the genome. Clock disruption leads to a wide spectrum of severe
health problems associated including chronic metabolic disorders, muscle waste
and cardiopathies. Recent evidence revealed that each cell and organ possesses
an intrinsic clock and that coordination between central versus peripheral
clocks is key for health. The underlying mechanisms that regulate the intrinsic
clock vs and its integration/interdependence on diet-induced stress are largely
unknown.
In this study we propose to investigate the role of chromatin cell memory
mechanisms for intrinsic clock transcriptional regulation and their functional
interplay with diet indices metabolic stress. We will focus on the mechanistic
role of Polycomb group proteins (PcG) mediated cell memory system on circadian
regulation and in particular the PRC2-Ezh1 complex, and its role in supporting
intrinsic clock functions both in gene silencing and activation in post-mitotic
skeletal muscle.
The outcome of this study will shed light on novel fundamental mechanistic
aspects underlying clock regulation, relevant for high societal impact
diseases, with the dual scope of improving health policies and indicating
possible novel therapeutic approaches.
Deliverables/Expectations
Deliverables
Unraveling the mechanistic
role of PRC2-Ezh1 mediated control of circadian clock regulation in protecting
and adapting skeletal muscle cells from high fat and fasting-induced metabolic
stress.
Faculty Name
Valerio Orlando
Field of Study
Field Of Study
Epigenetics