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Een driedimensionaal model van het axoneme, het op microtubuli gebaseerde supramoleculaire complex dat de beweeglijkheid van het sperma aandrijft. Credit: Miguel Leung
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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.
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.
Kılıç ZI, van Loenhout J, Chaillet ML, van Es RM, Sobrevals Alcaraz P, Vos HR, Noteborn WEM., Leung MR#
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Chaillet ML, van Loenhout J, Leung MR#, Burt A#, Tegunov D#
Leung MR
Leung MR, Sun C [...] Zeev-Ben-Mordehai T and Zhang R
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Leung MR, Zeng J [...] Zhang R, Zeev-Ben-Mordehai T
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Leung MR, Roelofs MC [...] Bloomfield-Gadêlha H, Zeev-Ben-Mordehai T
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Leung MR, Zenezini Chiozzi R [...] Heck AJR, Zeev-Ben-Mordehai T
Miguel Leung is vanaf oktober 2024 groepsleider bij het Hubrecht Instituut. De groep gebruikt structurele celbiologie (cryo-EM, cryo-ET, massaspectrometrie en AI-ondersteunde modellering) om de structuur, functie en evolutie van macromoleculaire complexen in zeer gespecialiseerde cellen te bestuderen. Om de complexiteit en diversiteit van cellulaire systemen volledig te begrijpen, gebruikt de groep structurele celbiologische methoden als instrumenten voor verkenning en ontdekking, waarbij deze methoden op uiteenlopende model- en niet-modelsystemen worden toegepast.
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We are actively recruiting young scientists at all levels. Please reach out to Miguel Leung for more information about available opportunities.
