Genomics of Inflammation

Principal Investigator:

• Dr Irina Udalova – i.udalova@imperial.ac.uk (personal page)

We are interested in genetic basis and molecular mechanisms of inflammatory diseases, with a particular focus on gene regulation. We employ novel genomic approaches to identify new key elements of acute and chronic inflammation. Our studies are focused on understanding the highly specific manner in which each gene is regulated, often by the same transcription factors. We have chosen the NF-kappaB/Rel family of transcription factors which are the key mediators of inflammatory response, to address this question.  

We investigate the hypothesis that the NF-kappaB activated enhancers have evolved to selectively regulate the expression of genes during inflammation by examining the biochemical and evolutionary properties of NF-kappaB binding sites in vertebrate genomes. We have demonstrated that despite the considerable degeneracy of NF-kappaB-like binding site consensuses, individual binding sites in the promoters of the immune and developmental genes are often well conserved.  

Our goal is to understand how the transcription factor-DNA binding preferences and molecular architecture of the enhancer translate into specific gene regulation. NF-kappaB binding sites divergent from the "consensus" sequence may function as important components of fine-tuned gene regulation. Moreover, NF-kappaB proteins can interact with a number of other regulatory factors, e.g. Interferon Regulatory Factors (IRFs). Such interactions are thought to provide an additional level of specificity in gene regulation and ensure a rapidly induced transcriptional response characteristic to inflammation.