Summary
Applying cutting-edge technology like cryo-electron tomography, subtomogram averaging and single-particle cryo-electron microscopy to sperm cells, I aim to uncover structural details of sperm centrioles.
As most other cells in the human body, sperm cells carry two centrioles called the proximal and the distal centriole. In the field of reproduction biology, it is widely accepted that these organelles are essential for the process of fertilization. One of their many important functions for this process is to provide centrioles for the zygote, as oocytes lose their own centrioles during maturation. Yet, the molecular mechanisms that determine their exact role in mediating fertility is not entirely understood.
Concurrently, infertility is increasing globally and so is the demand for treatment, commonly summarized as Assisted Reproductive Technology (ART). The success rate of ART is, however, only between 30-40% and even lower for women older than 35. One of the underlying reasons is that in up to 60% of the cases, male infertility is idiopathic. These numbers underpin the urge of improving our understanding of sperm biology and the molecular mechanisms of fertilization. This project defines three main objectives to achieve this:
1. Resolve the ultrastructure of sperm centrioles by applying cryo-electron tomography.
2. Isolation and high-resolution structure determination of the proximal centriole by cryo-electron microscopy.
3. Comparison of the centriole ultrastructure of sperm from fertile and infertile individuals.
A comprehensive structure-function investigation in a native setting will shed light on how centrioles are embedded within the neck of sperm cells. At high resolution, proteins that are associated to the centrioles and link them to surrounding structures can be identified. Finally, these findings will improve the understanding of male infertility, the diagnosis of such and ultimately increase the success rate of in vitro fertilization treatments.
As most other cells in the human body, sperm cells carry two centrioles called the proximal and the distal centriole. In the field of reproduction biology, it is widely accepted that these organelles are essential for the process of fertilization. One of their many important functions for this process is to provide centrioles for the zygote, as oocytes lose their own centrioles during maturation. Yet, the molecular mechanisms that determine their exact role in mediating fertility is not entirely understood.
Concurrently, infertility is increasing globally and so is the demand for treatment, commonly summarized as Assisted Reproductive Technology (ART). The success rate of ART is, however, only between 30-40% and even lower for women older than 35. One of the underlying reasons is that in up to 60% of the cases, male infertility is idiopathic. These numbers underpin the urge of improving our understanding of sperm biology and the molecular mechanisms of fertilization. This project defines three main objectives to achieve this:
1. Resolve the ultrastructure of sperm centrioles by applying cryo-electron tomography.
2. Isolation and high-resolution structure determination of the proximal centriole by cryo-electron microscopy.
3. Comparison of the centriole ultrastructure of sperm from fertile and infertile individuals.
A comprehensive structure-function investigation in a native setting will shed light on how centrioles are embedded within the neck of sperm cells. At high resolution, proteins that are associated to the centrioles and link them to surrounding structures can be identified. Finally, these findings will improve the understanding of male infertility, the diagnosis of such and ultimately increase the success rate of in vitro fertilization treatments.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101153233 |
| Start date: | 01-05-2024 |
| End date: | 30-04-2026 |
| Total budget - Public funding: | - 187 624,00 Euro |
Cordis data
Original description
Applying cutting-edge technology like cryo-electron tomography, subtomogram averaging and single-particle cryo-electron microscopy to sperm cells, I aim to uncover structural details of sperm centrioles.As most other cells in the human body, sperm cells carry two centrioles called the proximal and the distal centriole. In the field of reproduction biology, it is widely accepted that these organelles are essential for the process of fertilization. One of their many important functions for this process is to provide centrioles for the zygote, as oocytes lose their own centrioles during maturation. Yet, the molecular mechanisms that determine their exact role in mediating fertility is not entirely understood.
Concurrently, infertility is increasing globally and so is the demand for treatment, commonly summarized as Assisted Reproductive Technology (ART). The success rate of ART is, however, only between 30-40% and even lower for women older than 35. One of the underlying reasons is that in up to 60% of the cases, male infertility is idiopathic. These numbers underpin the urge of improving our understanding of sperm biology and the molecular mechanisms of fertilization. This project defines three main objectives to achieve this:
1. Resolve the ultrastructure of sperm centrioles by applying cryo-electron tomography.
2. Isolation and high-resolution structure determination of the proximal centriole by cryo-electron microscopy.
3. Comparison of the centriole ultrastructure of sperm from fertile and infertile individuals.
A comprehensive structure-function investigation in a native setting will shed light on how centrioles are embedded within the neck of sperm cells. At high resolution, proteins that are associated to the centrioles and link them to surrounding structures can be identified. Finally, these findings will improve the understanding of male infertility, the diagnosis of such and ultimately increase the success rate of in vitro fertilization treatments.
Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
24-11-2024
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