The goal of this project is to understand how different physiological signals are integrated to generate a strong, effective transcriptional response to infection. When Drosophila melanogaster are infected with bacteria, at least two parallel signaling events are engaged: detection of microbial products by pattern recognition receptors activates an NF-kB family transcription factor, while inhibition of nutrient-activated signaling pathways alters the activity of the transcription factor MEF2. Both these events are absolutely required for the normal immune response. We will use biochemical, genetic and computational approaches to decipher how these pathways work together in driving effective immunity.
Clark R I, Tan S W S, Péan C B, Roostalu U, Vivancos V, Bronda K, Pilátová M, Fu J, Walker D W, Berdeaux R, Geissmann F, Dionne M S. (2013) MEF2 is an in vivo immune-metabolic switch. Cell 155: 435-447.
Alic N, Andrews TD, Giannakou ME, Papatheodorou I, Slack C, Hoddinott MP, Cochemé HM, Schuster EF, Thornton JM, Partridge L. (2011) Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Mol Syst Biol 7: 502.
Lemaitre B, Hoffmann J. (2007) The host defense of Drosophila melanogaster. Annu Rev Immunol 25: 697-743.
Clark R I, Woodcock K J, Geissmann F, Trouillet C, Dionne M S. (2011) Multiple TGF-β superfamily signals modulate the adult Drosophila immune response. Current Biology 21: 1672-1677.
Dekker, J. (2006) The three 'C' s of chromosome conformation capture: controls, controls, controls Nature Methods - 3, 17 - 21