Gonadal Biology
The 4 laboratories active in this discipline are:
Ovarian Biology
Two primordial mouse follicles immunolabelled for the oocyte-specific protein VASA (red) and the intermediate filament protein Cytokeratin 8 (green). Nuclei are stained with DAPI (blue) - click for larger version
The work in this laboratory focuses on the cell biology, physiology and disorders of the ovary and is jointly led by Kate Hardy and Stephen Franks. It is supported by funds from the BBSRC and an MRC Programme Grant. Utilising a variety of approaches including detailed imaging, mathematical modelling, cell and tissue culture and molecular biological techniques, the principal aims of the group are:
- To understand the key processes that control initiation of growth and normal development of ovarian follicles (Lead: Kate Hardy)
- To understand the aetiology of polycystic ovary syndrome, a common ovarian disorder of women that has profound reproductive, endocrine and metabolic consequences (Lead: Stephen Franks)
Hormonal regulation of ovarian and testicular function
Metaphase II arrested mouse oocyte. Immunostained for beta tubulin (green) and DNA (blue) to visualise the meiotic spindle and chromosome alignment - click for a larger version
This group is lead by Ilpo Huhtaniemi, and it concentrates on physiology and pathophysiology of hormonal regulation of gonadal function, with special reference to the mechanisms of function of gonadotrophic hormones. The work is supported by MRC, EU and The Wellcome Trust. The translational goals of this research entail:
- To unravel the molecular mechanisms of gonadotrophin and gonadotrophin receptor function, and to study the functional consequences of mutations in the cognate genes
- To develop novel endocrine and non-endocrine strategies for male contraception and treatment of male infertility
- To understand the mechanisms and clinical significance of ageing- related decline in gonadal function
Ovarian cancer research
Figure showing fenmale genital tract and an abnormal mass in one ovary, sections from serous ovarian cancer frequently express WT1 protein, as seen in photograph shown on the right.
Translational research led by Sadaf Ghaem-Maghami focuses on immunology, immune regulation and immunotherapy of ovarian cancer. This work is funded by US government funding for research and Ovarian cancer Action. Based on systematic collection and immunological analysis of biosamples from patients with ovarian cancer we have identified promising targets for immunotherapy, such WT1, which is expected to lead to a vaccination trial in the near future in patients with ovarian cancer. The main focus of our current research is:
- Identification of potential immunological targets for treatment from our ongoing comprehensive immunological screen
- Development of clinically relevant immunological biomarkers
- Identification and development of targets for novel transgenic T cell therapies, including early phase studies in patients
Combining surgical and research expertise, we are also studying direct biological effects of targeted agents and immunological therapies on tumour cells in vivo using minimally invasive (laparoscopic) and novel cell fluorescence imaging techniques.
Chromosome cohesion
Metaphase I chromosomes from spermatocytes
This research is lead by Nobuaki Kudo. Aneuploidy-orientated diseases such as Down syndrome are caused by chromosome segregation errors during meiotic cell division of oogenesis and spermatogenesis. Frequencies of the errors are very high in aged women, but the reason is not understood. We seek to understand it by studying the mechanisms of chromosome cohesion and segregation in mammalian model systems. The work is supported by MRC, IOGT and Royal Society of London. The principal aims of the group are:
- To understand how meiotic prophase of oocytes is maintained for long period of time.
- To understand how meiotic chromosome functions are regulated by higher order chromosome structure in spermatocytes.
- To investigate meiotic chromosome abnormalities in abortive human spermatogenesis.
