Vertebrate Development and Regeneration
The Vertebrate Development and Regeneration group studies the mechanisms of cis-transcriptional regulation of genes and how mutations on non-coding cis-transcriptional regulatory sequences might impact in the development of some human diseases, in particular diabetes and pancreatic cancer. We employ genomic strategies to identify non-coding cis-transcriptional regulatory sequences and we perform genetic functional assays in zebrafish to evaluate the function of these sequences.
Defining when, where and how much genes are transcriptionally expressed is one of the major mechanisms that control organogenesis and organ function. Variations in these mechanisms might contribute to disease. The transcriptional regulation of genes is achieved by non-coding cis-regulatory elements (CREs) spread over large genomic distances and is important for the proper development, function and homeostasis of organs. Our major research interest is to understand these mechanisms of transcriptional regulation. We use the zebrafish as a vertebrate model and we focus in the pancreas, our organ of choice.
Over the last years, we have developed methods to detect, validate and disrupt CREs. Among these tools, we have developed the Zebrafish Enhancer Detection vector, that contains an in vivo reporter to test cis-regulatory activity of sequences. We have also developed the Expression Disruption vector, that allows to disconnect CREs from their target genes. Combining these tools with genome wide approaches such as Assay for Transposase-Accessible Chromatin, Chromatin Immunoprecipitation and Circularized Chromosome Conformation Capture, we are uncovering CREs active in the pancreas and we are accessing their biological function by disturbing their activity. This information will be extremely relevant to clarify the role of CREs in the development of two major pancreatic diseases Diabetes and Pancreatic Cancer.