Supervisors: Abir Mukherjee & Ali Fouladi

Department: Comparative Biomedical Sciences

Project Details:

The testicular function of spermatogenesis requires circulating hormone action as well as local regulators and a permissive niche provided by Sertoli cells. The extent of spermatogenesis in the adult is dependent on the number of Sertoli cells, which in most mammals reaches a maximum early in life and is maintained throughout life. Among the regulators of testicular development and function are the TGFb family ligands including activin1 which is crucial for generating the cohort of Sertoli cells to serve as germ cell niche in the testis.  FSTL3 is an endogenous inhibitor of activin expressed highly in the testis2. In FSTL3 deleted mice, the testicular size is increased, and function extended beyond the normal time-scale as seen in WT mice3. Importantly there is increased number Sertoli cells in FSTL3 KO mice testis.  

Fig.1: FSTL3 is important in limiting testicular size and inducing testicular regression in mice.

Top: Photographs showing enlarged testes in FSTL3 KO (KO) compared to FSTL3Flox/Flox (wild type - WT) mice from 3 and 10-month-old. Bottom: Histomorphometric analyses shows increased Sertoli and germ cell numbers in FSTL3 KO testes (Error bars = SEM, * = p<0.05). 

Our new data shows that there is actually an increase in Sertoli cell proliferation in the absence of FSTL34. To identify genes that are activated in a TGFb ligand-dependent manner in the testis we performed SMAD4 (transcription factor downstream of TGFb signalling) -ChIP Seq analysis using WT and FSTL3 KO testis. 

This project aims to Identify SMAD4-dependent candidate genes that are likely involved in activin-induced Sertoli cell proliferation. 

Requirements:

Essential  

• Must meet our standard MRes entry requirements
• Open to all Bio-science graduates

Desirable

• Basic biology laboratory skills including pipetting and microscopy.
• Knowledge of Cell and Molecular Biology
• Some experience in tissue culture

Funding:

Partially funded: e.g. the lab will be covering the project costs, with the MRes student expected to meet the course fees and their living expenses. 

International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees.

Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page.

References:

1. Itman C et al. 2006, Reproduction 132: 233.

2. Tortoriello DV et al. 2001, Endocrinology 142: 3426.

3. Oldknow KJ et al. 2013, Endocrinology 154: 1310.

4. Ballesteros Mejia R and Mukherjee A 2017, Endocrine Abstracts.

Deadline: June 6th 2025

For more information on the application process and English Language requirements see How to Apply.

Interviews will take place remotely (Teams, Zoom etc) within 4 weeks of the closing date.

We welcome informal enquiries - these should be directed to amukherjee@rvc.ac.uk