The Study of Protein Complexes in Gametogenesis

• Research type

  Research Study

• Full title

  The Study of Protein Complexes in Gametogenesis

• IRAS ID

  340922

• Contact name

  Matteo Allegretti

• Contact email

  matteoall@mrc-lmb.cam.ac.uk

• Sponsor organisation

  UK Research and Innovation (Medical Research Council is part of UKRI)

• Duration of Study in the UK

  5 years, 0 months, 1 days

• Research summary

  Gametogenesis is the process of generation of male (sperm) and female (egg) reproductive cells and it is an essential process for successful fertilisation. It is estimated that 1 in 6 people worldwide are affected by infertility. A clear understanding of the biological processes which take place during gametogenesis is essential for developing new therapeutic strategies in fertility and, simultaneously, in new contraceptive methods.

  Male gametogenesis initiates as a stem cell changes drastically its morphology, especially in the cell nucleus, where DNA is contained. Unique proteins are produced in testicular tissue that allow the nucleus to elongate and lose volume. Conversely, during female gametogenesis (oogenesis), the nucleus also undergoes morphological and structural changes, but these culminate with the formation of a nucleus several times larger than the somatic cells nucleus.

  This project aims to investigate how proteins involved in regulating nuclear shape during human gametogenesis assemble, interact with each other and how their structure changes.
  We will investigate:

  1) Nuclear Pore Complexes (highly regulated protein gates at the nuclear membrane that allow molecules to enter/exit the nucleus)
  2) proteasomes (degradation complexes for obsolete/malfunctioning proteins and organelles)
  3) LINC (Linker of Nucleoskeleton and Cytoskeleton, protein complexes that link the nucleus to the rest of the cell.)
  4) Cytoskeletal filaments (protein polymers that provide structure to the cell)
  5) Centrosome (cell organising centres)
  6) nuclear envelope protein complexes

  For maximum translational potential, we aim to investigate these questions using human tissue, using cutting-edge imaging techniques (cryo-electron tomography, super-resolution microscopy) combined with conventional and biochemical approaches (mass-spectrometry, immunohistochemistry, qPCR etc.), to provide insight into the basic molecular processes of gametogenesis in cells within or extracted from human tissue.

  Ultimately, our research aims to provide basic knowledge that may help inform clinical efforts in the development of new methods to fight infertility and create new contraceptive methods to reduce unintended pregnancies (120 million every year worldwide).

• REC name

  West Midlands - South Birmingham Research Ethics Committee

• REC reference

  24/WM/0226

• Date of REC Opinion

  22 Oct 2024

• REC opinion

  Favourable Opinion