Dr. Alberto Cebrian Serrano
Group Leader of the Genetics Unit – Institute for Diabetes and ObesityAlberto Cebrian-Serrano works at the intersection of genetics, metabolism and molecular biology to improve our understanding of metabolic disorders and develop ways to improve human health through bioengineering
Alberto Cebrian-Serrano works at the intersection of genetics, metabolism and molecular biology to improve our understanding of metabolic disorders and develop ways to improve human health through bioengineering
Academic Pathway
At the Institute of Diabetes and Obesity, Alberto Cebrian-Serrano’s expertise involves applying and developing CRISPR tools to model and treat diseases, including metabolic syndrome, obesity and diabetes. His research group focuses on genetically modified mouse models using DNA CRISPR targeting and also CRISPR-mediated activation technology to turn on silenced genes and mobilize endogenous defences against metabolic dysfunction. Specifically, his laboratory studies the conditional regulation of CRISPR activation, allowing for robust spatiotemporal control of endogenous gene expression whilst minimising genotoxicity and off-target effects. The mastery and further development of these genetic engineering tools are critical for bridging basic research with applied research.
Alberto Cebrian-Serrano joined Helmholtz Zentrum in 2017. Before moving to Munich, he launched is first steps with genome engineering as postdoctoral researcher at the Oxford University from 2015 to 2017 and at the Oldenburg University from 2013 to 2015. He received his PhD from the Technical University of Valencia and his Bachelor in Veterinary Medicine from the Autonomous University of Barcelona.
Expertise
Genetics
CRISPR/Cas9Genome editing
CRISPR-mediated activation
Professional Career
Group Leader at the Genetic Unit of the Institute of Obesity and Diabetes
Postdoc at the Oxford University (Transgenic Core)
Postdoc at the Oldenburg University (Neurogenetics group)
Selected Publications
Read more2023 Cell Metabolism
Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1
Until menopause, women have a lower propensity to develop metabolic diseases than men, suggestive of a protective role for sex hormones. Although a functional synergy between central actions of estrogens and leptin has been demonstrated to protect against metabolic disturbances, the underlying cellular and molecular mechanisms mediating this crosstalk have remained elusive. By using a series of embryonic, adult-onset, and tissue/cell-specific loss-of-function mouse models, we document an unprecedented role of hypothalamic Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (Cited1) in mediating estradiol (E2)-dependent leptin actions that control feeding specifically in pro-opiomelanocortin (Pomc) neurons. We reveal that within arcuate Pomc neurons, Cited1 drives leptin’s anorectic effects by acting as a co-factor converging E2 and leptin signaling via direct Cited1-ERα-Stat3 interactions. Together, these results provide new insights on how melanocortin neurons integrate endocrine inputs from gonadal and adipose axes via Cited1, thereby contributing to the sexual dimorphism in diet-induced obesity.
2021 Molecular Biology and Evolution
Altering the Binding Properties of PRDM9 Partially Restores Fertility across the Species Boundary
Sterility or subfertility of male hybrid offspring is commonly observed. This phenomenon contributes to reproductive barriers between the parental populations, an early step in the process of speciation. One frequent cause of such infertility is a failure of proper chromosome pairing during male meiosis. In subspecies of the house mouse, the likelihood of successful chromosome synapsis is improved by the binding of the histone methyltransferase PRDM9 to both chromosome homologs at matching positions. Using genetic manipulation, we altered PRDM9 binding to occur more often at matched sites, and find that chromosome pairing defects can be rescued, not only in an intersubspecific cross, but also between distinct species. Using different engineered variants, we demonstrate a quantitative link between the degree of matched homolog binding, chromosome synapsis, and rescue of fertility in hybrids between Mus musculus and Mus spretus. The resulting partial restoration of fertility reveals additional mechanisms at play that act to lock-in the reproductive isolation between these two species.
2017 Plos One
Genome manipulation in the mouse via microinjection of CRISPR/Cas9 site-specific nucleases has allowed the production time for genetically modified mouse models to be significantly reduced. Successful genome manipulation in the mouse has already been reported using Cas9 supplied by microinjection of a DNA construct, in vitro transcribed mRNA and recombinant protein. Recently the use of transgenic strains of mice overexpressing Cas9 has been shown to facilitate site-specific mutagenesis via maternal supply to zygotes and this route may provide an alternative to exogenous supply. We have investigated the feasibility of supplying Cas9 genetically in more detail and for this purpose we report the generation of a transgenic mice which overexpress Cas9 ubiquitously, via a CAG-Cas9 transgene targeted to the Gt(ROSA26)Sor locus. We show that zygotes prepared from female mice harbouring this transgene are sufficiently loaded with maternally contributed Cas9 for efficient production of embryos and mice harbouring indel, genomic deletion and knock-in alleles by microinjection of guide RNAs and templates alone. We compare the mutagenesis rates and efficacy of mutagenesis using this genetic supply with exogenous Cas9 supply by either mRNA or protein microinjection. In general, we report increased generation rates of knock-in alleles and show that the levels of mutagenesis at certain genome target sites are significantly higher and more consistent when Cas9 is supplied genetically relative to exogenous supply.
Networks and Affiliations
German Center for Diabetes Research
