Lluís Montoliu
Group Leader
Research summary
In our laboratory, we are interested in understanding how mammalian expression domains work and how they are organised within genomes. In particular, we focus on the identification and characterisation of genomic boundaries or insulators. By studying insulator elements, we aim to contribute to understanding of the functional and structural organization of vertebrate genomes. Insulators can be used effectively in biotechnological applications, as spacers, as boundaries, in any gene expression construct to be used in gene transfer experiments. We are searching for new insulator sequences in vertebrate genomes, through initial bioinformatic analyses.
Publications
Seruggia D, Josa S, Fernández A, Montoliu L. The structure and function of the mouse tyrosinase locus. Pigment Cell Melanoma Res. 2020 Oct 23.
Seruggia D, Fernández A, Cantero M, Fernández-Miñán A, Gomez-Skarmeta JL, et al. Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression. Sci Rep. 2020; 10: 15494.
Alzahofi N, Welz T, Robinson CL, Page EL, Briggs DA, et al. Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins. Nat Commun. 2020; 11: 3495.
Fernández A, Morín M, Muñoz-Santos D, Josa S, Montero A, et al. Simple Protocol for Generating and Genotyping Genome-Edited Mice With CRISPR-Cas9 Reagents. Curr Protoc Mouse Biol. 2020; 10: e69.
Sanzà P, Evans RD, Briggs DA, Cantero M, Montoliu L, et al. Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a. J Cell Sci. 2019; 132: jcs212035.
Mojica FJ, Montoliu L.On the Origin of CRISPR-Cas Technology: From Prokaryotes to Mammals. Trends Microbiol. 2016 Oct;24(10):811-20
Our laboratory is interested in understanding the underlying pathological mechanisms of a group of human rare diseases globally known as albinism, a heterogeneous genetic condition associated with mutations in at least 22 genes, characterised by visual impairment and pigmentation alterations. Our work on human rare diseases occurs within our participation in the CIBERER-ISCIII.
Our laboratory has generated and analysed new animal models to study visual abnormalities and different anomalies affecting retina development that are associated with albinism. In collaboration with Angel Carracedo (USC) and Carmen Ayuso (FJD), we have devised, within the CIBERER-ISCIII, a project for the universal genetic diagnostic of all known mutations in albinism. We are already applying this knowledge in cooperation with ALBA, the Spanish association in support of people with albinism and have been able to diagnose more than 120 families.
We are also interested in understanding the function of regulatory elements that are required to define gene expression domains in mammalian genomes. We have used the mouse tyrosinase locus (Tyr) as experimental model. This approach has allowed us to identify several key regulatory elements, such as genome boundaries or insulators, which protect the locus from surrounding genes and ensure the faithful gene expression pattern.
As a general strategy, we regularly use transgenic and genome-edited animals, zebrafish and mice to introduce different type of gene constructs in order to investigate the relevance of specific DNA regulatory sequences. The functional analysis of regulatory elements found within the intergenic non-coding genomic sequences can now be addressed more efficiently thanks to the efficient genome editing CRISPR-Cas9 tools. In Spain, where we have pioneered the application of CRISPR technology in mice, we have successfully implemented it in our laboratory and disseminated its use among colleagues by hosting short stays and organising ad-hoc workshops, seminars and courses.
CRISPR-Cas9 genome edited mice used to functionally identify key regulatory elements of the mouse Tyr locus (Seruggia et al. 2020, Sci. Rep.)
