Aging and Nutritional Stress Impacts on Cellular processes and RNA Regulation

Image caption: Drosophila embryo, smFISH for bcd RNA (magenta), P bodies (cyan), nuclei (orange).

Supervisor: Professor Tim Weil

As organisms age, homeostasis declines and cells are faced with critical challenges. These can  include an increase in DNA damage, protein aggregates, and loss of cell cycle regulation which can result in cancer and neurodegeneration. To combat the effects of aging, it is essential to understand what is changing at a subcellular level. Significant attention recently has focused on the effect of age-related stress on RNA-protein assemblies and larger biomolecular condensates. Both complexes have been shown to be important in mRNA regulation and to control proteins that can otherwise form disease-causing higher order structures in a cell.

This project aims to: (1) articulate the physical effects aging has on the formation and function of RNA-protein assemblies, and (2) test the impact of aging and nutritional stress on bimolecular condensates.

Aging and nutritional stress will be applied via environmental, genetic, and chemical manipulation to Drosophila eggs, prior to fertilisation, and to adult female flies. The primary condensate assayed in oocytes and embryos will be P bodies which are widely conserved and required for axis-patterning in Drosophila. Subsequent advanced microscopy and biochemistry will be used to assess the impact on mRNA localisation, protein expression, and condensate physical properties.

This in vivo project will help inform our understanding of aging and stress at a subcellular and molecular level. The work will have broad implications to our understanding of how animals maintain a healthy population of eggs and what therapeutic approaches can help to offset the deleterious effects of cellular aging.

For more information, please visit Weil Lab or contact Prof Tim Weil.

References 

Alberti S and Hyman AA, Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat Rev Mol Cell Biol 22, 196–213 (2021). doi: 10.1038/s41580-020-00326-6

He Y and Jasper H. Studying aging in Drosophila. Methods. 2014 Jun 15;68(1):129-33. doi: 10.1016/j.ymeth.2014.04.008.