About the project
Study how specific cell signalling pathways control stem cells and their ability to regenerate muscle. You could help counteract muscle loss during ageing, helping individuals affected by the muscle decline condition sarcopenia.
In this project, you'll investigate the impact of druggable phosphoinositide signalling pathways on the epigenetic status and transcriptional output of muscle satellite stem cells controlling their differentiation. The aim is to prevent satellite cell exhaustion by reprogramming nuclear phosphoinositide signalling, ensuring sustained differentiation and potentially alleviating sarcopenia symptoms.
As a PhD student, you will have the opportunity to explore the cutting-edge field of nuclear phosphoinositide (PPIns) signalling and its impact on genome architecture within satellite stem cells. Your work has the potential to directly improve the quality of life for individuals affected by sarcopenia reducing the cost of treating age-related muscle decline.
You will investigate how intricate subcellular changes within nuclear PPIns influence the epigenetic status of muscle stem cells controlling the expression of vital myogenic factors impacting on differentiation.
You’ll be equipped with a comprehensive toolkit of state-of-the-art technologies, including:
- proximity-based ligation assays
- CHiP (Chromatin Immunoprecipitation)
- high-throughput next-generation sequencing
- chromatin capture and bioinformatical analysis combined with advanced microscopy techniques
You'll be tasked with molecularly engineering the expression of lipid kinases and phosphatases to reprogram nuclear PPIns, reverse stem cell exhaustion and facilitate myogenic differentiation. You’ll do this using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) genetic editing and inducible expression systems.
The research will also involve investigating nuclear PPIns in satellite stem cells derived from young and old individuals in the Hertfordshire Sarcopenia study. You’ll gain invaluable skills and expertise in innovative methodologies in this immersive research and help develop novel strategies for maintaining the number and functions of satellite cells throughout the human lifespan.