Transcriptomics & Epigenomics

“Epigenetics” is “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” (Waddington, 1942).

Epigenome landscape
Monocytes and macrophages are key players in tissue homeostasis and immune responses. These tissue macrophages have trophic functions, maintaining tissue homeostasis and resolving inflammation. Monocytes provide a pool of macrophage precursors  that is recruited upon inflammatory challenges to mediate host-defence against pathogens, foreign antigens, or tissue damage. Transcriptomic and Epigenetic processes tightly regulate cellular function in health and disease, such as obesity and type 2 diabetes.  Recent studies from our team have allowed detailed characterisation of the transcriptional circuitry underlying monocyte and macrophage regulation (Toubal et al, JCI 2013, Dalmas et al. Nat Med 2016, Fan et al NatMed, Alzaid et al. JCI insight 2016, Drareni et al. Cell Reports 2018, Liang et al Nat Commun 2019). Upon differentiation and activation, genomic regions called enhancers are selected by lineage-determining and signal-dependent transcription factors. Enhancers are shown to be very dynamic, and activation of these enhancers underlies difference in gene transcription between monocytes, macrophages and their different subtypes.  Epigenetic enzymes regulate the functioning of these cells and targeting epigenetic enzymes has been proven to be a valuable tool to dampen inflammatory responses.

IMMEDIAB wants to establish a comprehensive understanding of the transcriptomic and epigenomic pathways that control monocyte and macrophage function and of the epigenetic enzymes involved in monocyte and macrophage differentiation and activation.

Future Directions

Our key challenges in the upcoming years will be to study epigenetic changes in human diabetes and to better understand how epigenetic pathways control the inflammatory repertoire in diabetic complications.

Transcriptomics and epigenetics team photo - Immediab lab