Characterising the Role of the Glucocorticoid Receptor in Gonadal Function through Conditional Gene-Targeting
Closing Date: 31 July 2020
This project will both increase our understanding of androgen signaling control within the reproductive system and have wider implications for other body systems, with obvious human relevance. The combination of these factors means this project is likely to produce a series of high impact publications.
Background Chronic or repeated stress and illness are known to reduce testosterone production from the gonad (testis/ovary) but a mechanism for this has yet to be defined. Stress hormones, act via their receptor, glucocorticoid receptor (GR). GR is expressed in the Leydig cells (LCs) of the testis, theca cells of the ovary and germ cells (GCs), yet, how GR controls these cell types is also unknown. Understanding how GR signaling fundamentally controls gonadal function and testosterone production has major implications for our understanding of the control of male and female life-long health.
This project will use a well-established gene-editing tool known as the Cre/Lox recombinase system. This technology allows us to genetically modify GR to remove it from the gonad. We aim to use two different types of Cre mouse lines; Cyp17a1 Cre which is specifically expressed in Leydig cells and theca cells; and the Vasa-Cre which is specifically expressed in germ cells.
By doing this, we are able to dissect the role stress signaling plays in the gonad and its impact on testosterone production
Project summary overview:
- Characterise Glucocorticoid Receptor KO in both gonadal (Cyp17a1-Cre) and germ cells (Vasa-Cre)
- Establish the expression pattern of androgen receptor and androgen profile following perturbation of glucocorticoid receptor signaling in the male and female gonad.
- Establishment of the role of GR signaling in gonadal development All breeding is underway, antibodies are proven, and archived tissue is available. Health/Wealth benefits
This project focusses on detailed molecular genetic analysis of GR, which, if perturbed is known to cause a range of human diseases. This project will both increase our understanding of androgen signaling control within the reproductive system and have wider implications for other body systems, with obvious human relevance. The combination of these factors means this project is likely to produce a series of high impact publications
PhD Scholarship details
Funding: $28,092 per annum (2020 rate) indexed annually. The living allowance scholarship is for 3.5 years and the tuition fee scholarship is for four years.
Supervisor: Professor Lee Smith
Available to: Domestic students
The candidate will join a growing multi-disciplinary team, consisting of experts in the field. Applicants should have a strong work ethic, self-motivation, developed communication, and teamwork skills. We are seeking applications from individuals who have completed first-class or second-class upper honors degree in a Biomedical Science or equivalent degree with laboratory experience.
Professor Lee Smith
Dr Anne-Louise Gannon
Interested applicants should send an email expressing their interest along with scanned copies of their academic transcripts, CV, a brief statement of their research interests and a proposal that specifically links them to the research project.
Please send the email expressing interest to L.B.Smith@newcastle.edu.au by 5pm on 31 July 2020.
Applications Close 31 July 2020
|Contact||Professor Lee Smith|
|Phone||(02) 4921 5906|
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