PhD Opportunity(See https://www.newcastle.edu.au/study/research/phd-scholarships/phd-scholarships/male-germline-regeneration-and-fertility-restoration-after-genotoxic-damage)
Male fertility relies on spermatogonial stem cells (SSCs) that generate sperm. After chemotherapy, SSCs can be damaged and the recovery of fertility dependent on testis regeneration by surviving SSCs. This project aims to understand the mechanisms underlying SSC survival and regeneration.
Integrity and regenerative capacity of many tissues are dependent on resident stem cells. While stem cell failure is appreciated to underlie declining tissue function with age and degenerative diseases, cellular pathways maintaining stem cell activity are incompletely understood.
Spermatogonial stem cells (SSCs) mediate sustained spermatozoa production and recovery of fertility following germline damage by genotoxic therapy. SSCs are particularly sensitive to chemotherapeutic agents and radiation and patients often at a high risk of becoming infertile.
Mechanisms that mediate therapy resistance plus regenerative capacity of SSCs and support germline recovery are essentially unexplored. Moreover, long-term effects of genotoxic treatments on the function of surviving SSCs are unclear.
In this project we will characterize changes in functional state of SSCs plus their supportive niche after damage and during germline regeneration. Factors controlling the response of SSCs to genotoxic drugs and their regenerative response will be characterised through an innovative pipeline involving single cell genomics, SSC transplantation and testis organoids.
This study will provide invaluable insight into pathways underpinning male germline restoration following damage and can identify therapeutic targets to help preserve fertility of cancer patients.
