Functional genomics of the MHC
We are using functional genomic approaches to define genetic variants that are responsible for the association of genetic variation in the Major Histocompatibility Complex (MHC) with susceptibility to autoimmune, infectious and inflammatory disease. Recent work in our lab has highlighted the extent of allele-specific differences in gene expression in human lymphoblastoid cell lines and primary immune cells. We aim to resolve the functional consequences of genetic and epigenetic variation in the MHC for transcriptional regulation using high throughput sequencing for DNA sequencing, transcript quantification (RNA-seq) and chromatin profiling (ChIP-seq) at allele-specific resolution, together with analysis of epigenetic modifications, noncoding RNAs, alternative splicing and DNA methylation. We compliment this with detailed functional characterisation of the mechanisms whereby specific regulatory variants exert an effect. This project is sponsored by the European Research Council.
Daniel obtained his B. Sc (Hons) in Cell and Molecular Biology from the National University of Singapore (NUS). Following that was a three-year stint as a Research Associate with the National Cancer Centre Singapore where he established platforms for high-throughput transcriptomics. Using these, he participated in a research project examining virulence mechanisms in B. pseudomallei, a microbial pathogen implicated in biological warfare. In 2005, Daniel embarked on a Ph.D project with the Ewbank Group at the Centre d’Immunologie Marseille-Luminy (CIML) in France. This was co-funded by Sanofi-Aventis as part of BioTox, a French government initiative to defend against harmful biological agents. With the aid of the model organism, C. elegans his efforts here were underpinned by an immuno-genomics approach to dissect the innate immune system. He was also concurrently employed by INSERM as a Research Engineer and established a microarray facility at the CIML. Daniel joined the Genomics Group in 2008 where he is currently involved in the development of an experimental platform for deciphering protein-DNA interactions. In this, transcription factors like NFKB and Interferon Regulatory Factors (IRFs) which function in immune defence would be expressed as physiologically active molecules. Detection systems then profile at high resolution their binding to specific motifs on nucleic acid-probes. Information generated will be complementary to existing methodologies for the analysis of transcription factor-activity.Keywords: MHC, Functional Genomics, Genetics, Gene Expression, Epigenetics