Ovarian ageing is a naturally occurring physiological process resulting in declining fertility and cessation of ovarian function midlife at menopause. The ovary ages chronologically faster than other organs, however the mechanisms governing the processes of ovarian ageing and senescence remain to be fully understood. There is increasing evidence that the architecture and matrices that support ovarian function are dynamically regulated during ageing. The overall aim of this PhD project is to determine how the ovarian architectural landscape is modulated across the reproductive lifespan of the ovary. The candidate will become proficient in and use a combination of approaches including super resolution imaging via atomic force microscopy and photoactivated light microscopy (PALM), mechano-modulation of 3D ovarian follicle organoid cultures, as well as molecular and biochemical techniques including immunohistochemistry and qPCR. Pre-clinical mouse models will be used for this work, with potential for expansion into human ovarian tissue. Yr1 objective: to utilize atomic force microscopy to map ovarian stiffness across reproductive lifespan. Yr2 objective: to map changes in extracellular matrices across reproductive lifespan. Yr3 objective: to utilize mechano-modulate 3D ovarian follicle cultures to understand how stiffness and mechanotransduction regulates ovarian follicle function. The outcomes of this will provide key insights into how architectural changes in the ovary modulate ovarian function across ageing, to begin to identify new strategies to conserve and/or extend ovarian function and lifespan.
Combining super resolution imaging with physiological systems to understand the mechano-regulation of ovarian ageing
Representative Publications
1. GP Johnson, C Onabanjo, K Hardy, VY Butnev, GR Bousfield, KC Jonas (2022) Follicle stimulating hormone glycosylation variants distinctly modulate pre-antral follicle growth and survival. Endocrinology 163 (12): bqac161. DOI: 10.1210/endocr/bqac161;
2. UT Agwuegbo, E Colley, AP Albert, VY Butnev, GR Bousfield, KC Jonas (2021) Differential FSH glycosylation modulates FSHR oligomerisation and subsequent cAMP signaling. Frontiers in Endocrinology, 12:765727. DOI: 10.3389/fendo.2021.765727;
3. KC Jonas*, A Rivero Müller, O Oduwole, H Peltoketo, I Huhtaniemi, (2021) The luteinizing hormone receptor knock-out mouse as a tool to probe the in vivo actions of gonadotropic hormones/receptors in females. Endocrinology, 162(5):bqab035 DOI: 10.1210/endocr/bqab035
1. Blache U, Stevens MM, Gentleman E (2020) “Harnessing the secreted extracellular matrix to engineer tissues.” Nature Biomedical Engineering. doi: 10/1038/s41551-019-0500-6;
2. Jowett GM, Norman MDA*, Yu TTL*, … Neves JF†, Gentleman E† (2021) “ILC1 drive intestinal epithelial and matrix remodelling.” Nature Materials. 20:250-9. †Joint corresponding authors. doi:10.1038/s41563-020-0783-8 ;
3. Normal MDA,… Gentleman E (2021) “Measuring the elastic modulus of soft culture surfaces and three-dimensional hydrogels using atomic force microscopy.” Nature Protocols. doi: 10.1038/s41596-021-00495-4