Department Molecular Genetics
Principal investigator Alex Zelensky
E-mail address a.zelensky@erasmusmc.nl
Website https://anz.craft.me/M8gxQ8bJPoKgqz
Live cell microscopy imaging of mammalian RAD51
Suitable as a BEP? No
Suitable as a MEP? Yes
Suitable as an Academic Research Project? No
Techniques:
- Live cell microscopy (spinning disk confocal)
- Advanced image analysis
- CRISPR/Cas9 genetic engineering
RAD51 is the central eukaryotic homologous recombination (HR) protein. It traces back to the origins of life and prominently features in cancer research. Up until recently, it was not possible to study RAD51 in living cells—due to its fundamental role and conservation, adding fluorescent tags results in lethality or loss of function. A breakthrough study solved this problem in yeast and led to a series of exciting follow-ups. We managed to do this in mammalian cells and achieve unprecedented temporal resolution by using a highly photostable fluorophore, creating endless research opportunities and stunning movies. A motivated MEP student can contribute to further use and development of the new system.
Further reading (click to link to article)
Breakthrough yeast study: doi:10.1038/s41594-023-01065-w
The “string theory of meiosis”
Suitable as a BEP? No
Suitable as a MEP? Yes
Suitable as an Academic Research Project? No
Techniques:
- Immunofluorescent staining
- Super-resolution microscopy imaging
- Quantitative analysis of microscopic data
- Thought experiments.
To ensure faithful segregation of genetic information into gametes during meiosis, each of 40/46 mouse/human chromosomes has to pair up with its homolog: find homologous sequences among billions of non-homologous nucleotides, maneuver through the confined and crowded nuclear space without getting tangled and stuck, get organised in loops along proteinaceous axis, align side by side and form a linked bivalent. The complexity of this process makes it seem magical, and homologous recombination is central to it. We stumbled upon an observation of long tensed DNA “tethers” between homologous chromosomes at the early stages of meiotic pairing and came up with a model that we believe explains a lot in this mysterious process. A talented MEP student could help with (dis)proving it.
Further reading (click to link to article)
https://www.biorxiv.org/content/10.1101/2023.10.06.561239v1