Project No. 2415

STANDARD PROJECT

Primary Supervisor

Prof Nullin Divecha – University of Southampton

Co-Supervisor(s)

Prof Anastasia Callaghan – University of Portsmouth

Summary

This Ph.D. project offers a unique opportunity to explore a critical aspect of aging—sarcopenia—and its underlying mechanisms.

Our research aims to unravel the enigmatic interplay between nuclear polyphosphoinositides (PPIns) and muscle stem cell function during the aging process.

Rationale:

Aging brings with it a myriad of health concerns, with sarcopenia at the forefront. Characterized by the progressive loss of muscle mass and function, sarcopenia not only affects mobility but also leads to insulin resistance, physical disability, and increased mortality risk. Addressing the scientific underpinnings of sarcopenia is a rational and imperative endeavor. This project seeks to explore the role of nuclear PPIns, lipid molecules involved in fundamental cellular processes, in mitigating the effects of sarcopenia.

Importance: Enhancing our knowledge of muscle stem cell biology and aging is crucial. Decoding nuclear PPIns’ links with muscle stem cells, may lead to interventions preserving elderly muscle function and quality of life

Project Objectives:

1. Characterize Nuclear PPIns in Muscle Stem Cells:Study nuclear PPIns in muscle stem cells from various age groups, focusing on aging-related changes.

2. Determine Nuclear PPIns’ Impact on Muscle Cell Differentiation: Manipulate nuclear PPIns using advanced cell biology techniques to assess effects on muscle cell differentiation, especially myogenic differentiation.

3. Explore RNA Splicing Factors’ Role: Investigate RNA splicing factors with RNA binding motifs and their influence on nuclear PPIns regulation in muscle stem cells.

4. Utilize Advanced Imaging and Structural Techniques: Apply high-definition cell microscopy and biophysical methods, including RNA array technology, to visualize and analyze molecular interactions in muscle stem cell biology.

5. Apply Bioinformatic Analysis: Conduct extensive bioinformatic analysis on large datasets generated during the project for insights.

Candidate Qualities:

• Profound interest in cellular and molecular biology, particularly stem cell research.
• Wish to utilise advance techniques, including CRISPR-CAS9 gene editing and high-definition cell microscopy.
• A passion for scientific inquiry