Principal Investigator – Junior Research Group Leader Developmental Genomics Laboratory
Dr. Alvaro Rada-Iglesias
The team led by Dr. Alvaro Rada-Iglesias is researching how gene expression is regulated during embryogenesis and how its misregulation might lead to human disease. The research group has developed a method for the genome-wide identification of transcriptional regulatory DNA sequences. The goal is to investigate these sequences for non-coding mutations, in order to decode the genetic basis of human disease.
Our research: Dr. Alvaro Rada-Iglesias and his team are investigating the regulation of gene expression during mammalian development. They are trying to discover how stem cells can develop into specific cell types in early embryogenesis, and what makes further differentiation possible. The researchers believe that changes in this early gene expression due to non-coding genetic variation may contribute to the development of congenital diseases.
Our successes: The scientists have developed a successful method for the genome-wide identification of regulatory DNA sequences. These sequences control DNA expression and are decisive in switching genes on and off during embryological development. The genomic approaches developed by Dr. Rada-Iglesias team are now being used by research groups in other laboratories.
Our goals: Working on the assumption that mutations in regulatory DNA sequences may contribute to human disease, Dr. Rada-Iglesias and his team aim to identify these mutations and characterize their functional consequences. Although focusing on congenital disease, the team’s approach should be broadly applicable to many other human disorders. Ultimately, the main goal is to understand the genetic basis of human disease, which might result in the development of novel therapeutic approaches.
Our methods/techniques: The team is working with embryological stem cells in vitro and chick embryos in vivo, using methods belonging to the fields of genomics, biochemistry, and molecular biology. In addition, the group is using next-generation sequencing techniques, such as RNA sequencing (RNA-seq), chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq), and 4C-seq, which allows the investigation of chromatin interactions.
Figure 1: Combinatorial analysis of ChIP-seq data for a number of histone modifications and transcriptional coactivators (i.e. p300) allows the identification of active enhancers (adapted from Rada-Iglesias et al., Nature 2011).
Figure 2: Bioinformatic pipeline employed to predict SNPs occurring within active hNCC enhancers and potentially altering NR2F1/2 binding to these regulatory elements (adapted from Rada-Iglesias et al., Cell Stem Cell 2012).