Supervisor: Dr. Anchel De Jaime Soguero
Genome and proteome integrity are crucial for proper embryo development, but how both are monitored across lineage specification, as well as how they are shaped by the microenvironment, remain open questions. In humans, spontaneous miscarriage rates are elevated (~70% pregnancies), and while the main causes are poorly understood, chromosome alterations and proteostasis disruption emerge as potential drivers.
We have recently identified that morphogenetic and patterning signals regulate DNA replication dynamics and chromosome segregation fidelity in a lineage-specific manner (De Jaime-Soguero et al. Nature Communications, 2024)1. These findings: i) suggest that specific lineages respond and mitigate differently replicative stress, driving chromosomal mosaicism in a cell fate-dependent manner, and ii) propose a rational for the elevated levels of aneuploidy and chromosomal mosaicism in miscarriage embryos. We seek a motivated doctoral researcher to investigate developmental resilience during early embryogenesis and lineage specification towards other stress sources, including protein folding stress (ER stress) or heat-shock stress. In particular, the candidate will tackle the following related questions:
- What is the physiological relevance of these cellular stresses in different early mammalian embryonic lineages? How do the lineages mitigate/cope with them?
- What is the bidirectional link between these stresses and genome/chromosome stability?
- How does the mouse and human embryo cope with cellular stress during early stages and what is the play on it of embryonic and extraembryonic lineages?
Our recently formed group (De Jaime-Soguero lab, IRIBHM-ULB) has expertise in cellular signaling and quantification of genome stability, pluripotency and early lineage specification in 2D, novel 3D stem cell-based embryo models (including gastruloids and EiTiX embryoids)2–4 and ex vivo mouse embryo experimentation. We collaborate with Isabelle Migeotte lab at IRIBHM, which has long-standing expertise in gastrulation and whole-embryo live imaging, with the Department of Gynaecology at ULB for human embryo work and with bioinformaticians at the home institute and at EMBL Gene Core (Heidelberg). The candidate will implement and combine the abovementioned techniques with single cell OMICs (single cell-genome and transcriptome sequencing, scEdU-sequencing) to dissect fate, genome and protein stability in a cellular stress context.
Qualification profile
You hold a MsC in Life Sciences or Bioinformatics and have a strong interest in molecular, cell or developmental biology. Experience with cloning and/or R coding for bioinformatic analysis is a plus. You have strong analytical and communication skills, are enthusiastic and critical thinker. Fluency in English is required, as well as to be able to work well in an international environment.
We offer
We offer at IRIBHM state-of-the-art facitilities and resources to fulfill you research project. Our laboratory offers: i) a healthy lab culture and lively international environment, with English as working language, ii) access to advanced training in scientific and professional skills, including the possibility to join scientific congresses and workshops iii) supervision and support tailored to your career perspectives, iv) and interdisciplinary collaborations involved to leverage the project in aspects where we lack the expertise.
References:
1. de Jaime-Soguero, A. et al. Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress. Nat. Commun. 2024 151 15, 1–22 (2024).
2. Method of the Year 2023: methods for modeling development. doi:10.1038/s41592-023-02134-0.
3. Moris, N. et al. An in vitro model of early anteroposterior organization during human development. Nature 582, 410–415 (2020).
4. Lau, K. Y. C. et al. Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development. Cell Stem Cell 29, (2022).