Control of reproductive aging by germline stem cells

Summary

This research project aims to understand the mechanisms of stem cell exhaustion during aging, focusing on germline stem cells in C. elegans, to identify potential strategies for preserving stem cell function and promoting healthy aging in humans.

What they want

The project proposes two specific aims to test innovative hypotheses regarding stem cell exhaustion. Aim 1 will elucidate mechanisms of Notch pathway regulation during adult germline stem cell aging by monitoring LAG-2 ligand expression in the DTC niche and analyzing LAG-2 ligand and Notch receptor function. Aim 2 will determine how sensory neurons regulate the DTC niche to mediate germline stem cell aging by analyzing the DAF-3 binding site in the lag-2 promoter and the DAF-3 and DAF-5 transcription factors, examining protein expression, stem cell dynamics, and progeny production.

Deliverables

Elucidation of mechanisms of Notch pathway regulation during adult stem cell aging in the germline
Determination of how sensory neurons regulate the DTC niche to mediate germline stem cell aging
Establishment of how LAG-2 ligand expression is regulated during aging
Data on whether LAG-2 ligand and/or GLP-1/Notch receptor are sufficient to sustain stem cell activity during aging
Data on how neuronal signals control the niche and stem cells during aging
A foundation of knowledge that may stimulate innovative approaches to preserve stem cell function and promote healthy aging in humans

Technical requirements

Use of C. elegans as a model organism
Monitoring LAG-2 ligand expression in the DTC niche
Analysis of LAG-2 ligand and Notch receptor function
Analysis of the DAF-3 binding site in the lag-2 promoter
Examination of DAF-3 and DAF-5 transcription factors
Examination of multiple levels of organization including protein expression, stem cell dynamics, and progeny production