Department

Department of Cell Nucleus Plasticity

Head

Helena Fulkova, PhD

Website

http://www.iem.cas.cz/en/research/departments/department-of-cell-nucleus-plasticity/

Project title

Molecular and functional analysis of the nucleolus in 3D genome organization in early embryo development

Supervisor

Helena Fulkova, PhD

Project description

Eukaryotic genomes exhibit a complex 3D architecture, important for the correct execution of gene expression programs. Together with the nuclear periphery, the nucleolus is a major genome organizing structure. Upon fertilization, the parental genomes undergo an extensive spatial and epigenetic remodeling to establish totipotency. How the nucleolus participates in the 3D genome organization and correct execution of the developmental program is unknown. The aim of the project is to determine the role of embryonic nucleoli in early development using a synergistic multi-omics approach with focus on the novel Nucleolar-DamID technology to identify and functionally characterize parental genomic domains contacting the nucleolus in embryos. By artificially tethering specific sequences to nucleoli using a CRISPR/Cas9-based system, we will determine the molecular and functional contribution of nucleoli to 3D genome organization in development. The results will widen our molecular understanding of early development and provide information of high medical relevance, especially for reproductive medicine. The project will be conducted in collaboration with the University of Zurich, Switzerland.

Candidate profile

We are looking for a highly motivated student to participate in this challenging project. The skills required are; intermediate level methods in molecular biology, good knowledge of and experience in developmental and/or reproductive biology. A background in micromanipulations and confocal microscopy would be beneficial. The candidate should demonstrate strong work ethics and thrive in a highly competitive environment. Independent thinking, a strong motivation to learn, adapt and develop new methods is a must. The position will require the successful candidate to work with animals (mice) and animal material. The candidate should have good English skills as exchange of students/staff with foreign laboratories throughout the project will be required. Good communication skills is a necessity due to the collaborative nature of the project. Number of positions available: 1. Duration of the project: 3+ years.

Suggested reading

• The nucleolus-like and precursor bodies of mammalian oocytes and embryos and their possible role in post-fertilization centromere remodelling. Biochem Soc Trans. 2020 Apr 29;48(2):581-593. doi: 10.1042/BST20190847.
• The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition. Development. 2014 Apr;141(8):1694-704.
• The maternal nucleolus is essential for early embryonic development in mammals. Science. 2008 Feb 1;319(5863):613-6.

Application form