CRISPR-Cas in vivo optimizations to understand early vertebrate development and human diseases
Miguel Angel Moreno Mateos
While the applications of CRISPR-Cas systems have been extremely useful in eukaryotic cells, their implementation and optimization have been largely directed to ex vivo systems such as mammalian cell cultures. However, in vivo CRISPR-Cas applications within live animal systems usually require additional modifications and adjustments. In the Moreno-Mateos lab we are interested on the implementation and optimization of different CRISPR-Cas systems using zebrafish and other in vivo model systems.
Beyond novel and optimized CRISPR-Cas approaches in zebrafish, we use molecular and cellular biology, functional genomics to better understand early vertebrate development and human diseases. In particular, we are interested on a fundamental biological process, the maternal-to-zygotic transition (MZT). The MZT is a complex cellular reprogramming event in vivo driving the beginning of a new life. During the MZT, the maternal contribution (mainly RNA and proteins) is responsible for transcription activation in the embryo whose genome is initially silenced. After that, this maternal contribution is eliminated in a controlled manner. Despite recent advances, the molecular mechanisms that trigger and orchestrate early development and the MZT are not yet fully understood. Therefore, our lab is also interested in uncovering new regulatory factors controlling early development that will help to better understand cell reprogramming in vivo.
Finally, we are, in collaboration with other labs, using zebrafish to model different human diseases and developmental disorders such as retina degeneration and prion-associated diseases.
All together, we will contribute to the generation and optimization of new tools in biotechnology for in vivo applications as well as to the discovery of new factors of interest in developmental biology, cell reprogramming and in biomedicine in general.
Fig 1. Cartoon of different CRISPR-Cas systems used in the lab to be injected in one-cell-stage zebrafish embryos. On the right pictutes of F0 zebrafish loss-of-fucntion mosaic mutants of tyr (tyrosynase) and tbxta (notail) genes.