Deciphering stress response in healthy aging

About the Project

Details of the Project

Background: When organisms encounter stressors such as heat, nutrient deprivation, or oxidative damage, cells form stress granules (SGs)—aggregates of proteins and RNA. SGs protect mRNAs and proteins from degradation, allowing cells to resume normal functions once stress is removed. However, stress responsiveness declines with age. Aging cells accumulate damaged macromolecules due to impaired proteostasis and experience elevated oxidative stress, creating a detrimental feedback loop in which stress accelerates aging, and aging weakens stress responses.

Hypothesis: Aging represents a gradual accumulation of chronic cellular stress that disrupts SG dynamics. Aberrant or persistent SGs may impair stress adaptation. Properly balanced SG dynamics may therefore support healthy aging and extend lifespan.

Importance: Role of SG in organismal aging remains poorly understood. C. elegans offers a powerful model to study aging-related processes due to its short lifespan, genetic tractability, conserved pathways and transparency, allowing high-resolution live microscopy.

Aim: This project aims to examine how SG composition, dynamics and stress responsiveness change with age using three objectives:

1. Assess age-dependent SG composition. SGs will be purified from young and old worms under oxidative or heat stress and analysed by mass spectrometry and RNA-seq, alongside core SG protein-level changes by SDS-PAGE and Western blotting.
2. Determine how impaired SG function affects aging. Using wild-type and core SG gene mutants, we will measure lifespan, fecundity, locomotion, and additional aging markers.
3. Evaluate age-related changes in stress recovery. SG dynamics will be monitored in young and old wild-type and SG gene mutant animals to test whether aging compromises SG dynamics.

Overall, this project will uncover physiological changes in stress response as we age and provide a springboard for future validation of identified candidates for promoting healthy aging.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

a] a First or Upper Second Class award in their undergraduate degree, in a relevant subject.

OR

b] a First or Upper Second Class award in their undergraduate degree, and a Merit or Distinction in a Masters degree, both in a relevant subject.

Qualifications from overseas institutions will be considered, but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Location

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly.