Periodic Reporting for period 2 - METAMOLE (Naked mole-rats to mice: metabolic reprogramming to prevent ischaemic injury)
Período documentado: 2022-07-01 hasta 2023-12-31
The overall Objectives is to:
1. Understand the molecular underpinnings behind the naked mole-rats rewired metabolism and its maintained neonatal state in the heart. Insights from these studies provide important clues to understand what makes a regenerative heart and the metabolic milieu and regulation required to deal successfully with stressful cellular environments found in heart disease (eg. hypoxia, ischaemia/reperfusion)
2. Introduce naked mole-rat traits into the mouse via transgenesis. The traits introduced will be those that we believe differentiate this species from the mouse and offer it optimized fitness to deal with ischemia or potentially give rise to regenerative capacity. This objective will test whether a single candidate alone, first discovered in the naked mole-rat, can be targeted or introduced to achieve therapeutic outcome in conditions of heart injury or heart failure.
3. Investigate the regenerative capacity of the naked mole-rat heart and thus establish the naked mole-rat as the first adult mammalian model of heart regeneration.
2. We have overexpressed the fructose transporter GLUT5 in the mouse and have validated the overexpression of the transporter across different tissues including the heart. we are now analysing ischaemia/reperfusion studies performed on GLUT5 transgenic hearts ex vivo to understand whether, in the same capacity as in the naked mole-rat, increased fructose metabolism protects mouse hearts from injury associated with ischaemia/reperfusion.
3. We are in the process of analysing the intrinsic ability of the naked mole-rat heart to regenerate post-injury.