Leung: Structural cell biology Back to research group The Leung group aims to understand the form, function, and evolution of highly specialized cells. The group’s research focuses on macromolecular assemblies in gametes (sperm and egg cells) and their roles in reproduction and early development. The vast majority of animal species reproduce through the fusion of two specialized cells called gametes – the sperm and the egg. The sperm loses most of its cytoplasm and many of its organelles, resulting in a highly streamlined form adapted for its sole function: finding and fusing with its partner gamete. The egg cell, on the other hand, stockpiles cellular resources needed to initiate and provision the elaborate molecular programs of development in the early embryo. As a result, the egg grows to be one of the largest cells in the body. Deficiencies in gamete form and function lead to infertility, which affects nearly 1 in 6 people worldwide. On the other side of the same coin, gamete function is an important target for developing novel contraceptives, for which there is a glaring unmet need as nearly half of all pregnancies worldwide are unplanned. Since reproduction is crucial for species survival, improving reproductive biotechnologies for diverse organisms will be important for biodiversity conservation in a changing world. Progress towards these reproductive health pursuits would benefit immensely from enhancing our knowledge on gamete form and function across the tree of life. Examples of protein complexes and organelles in mammalian sperm visualized by cryo-electron tomography. Credit: Miguel Leung. Copyright: Hubrecht Institute. A three-dimensional model of the axoneme, the microtubule-based supramolecular assembly powering sperm motility. Credit: Miguel Leung. Copyright: Hubrecht Institute. The core techniques we use in our research are cryo-electron microscopy and cryo-electron tomography. We use these techniques to image native multi-protein complexes either isolated directly from cells/tissues or in situ within the context of the unperturbed cellular environment. We apply advanced image processing approaches and artificial intelligence-assisted protein structure modelling, supplemented with proteomics and cross-linking mass spectrometry, to build molecular atlases of these complexes. We then use our structural models to inform targeted functional and genetic studies, aimed at dissecting the roles of individual protein components. In parallel, we take advantage of the immense morphological diversity of gametes across the animal kingdom to understand how macromolecular assemblies evolve and diversify in relation to changes in fertilization environment or reproductive strategy.
