Background and current state of research
Doctoral researcher of the first generation: Yask Gupta (He is now associated.)
Susceptibility to chronic inflammatory diseases is determined by the interaction of genetic and environmental risk factors. In particular, resident microbial communities as environmental factors are the subject of intense scrutiny due to numerous observations of differences between healthy and diseased states. However, whether differences in microbial communities are of primary etiological importance or secondary to the altered inflammatory environment remains largely unknown. We hypothesize that naturally occurring variation in the host genome influences the composition of the resident microbiota, and this in turn influences susceptibility to chronic inflammatory diseases. To test this hypothesis we will systematically describe and manipulate the microbiota of genetically distinct mouse inbred strains that differ in susceptibility to chronic inflammatory diseases.
Our goals
We will test the hypothesis that naturally occurring variation in the host genome influences the composition of the resident microbiota, and this in turn influences susceptibility to chronic inflammatory diseases.
How to get there
We want to
- characterize the gut and skin microbiota of inbred mouse strains that differ in susceptibility to chronic inflammatory diseases using high throughput 16S rRNA gene sequencing (barcoded 454-pyrosequencing)
- determine whether changes in the microbiota correlate with disease in models of spontaneous chronic inflammation
- proceed with QTL and positional cloning of host genes influencing the composition of the microbiota, provided preliminary experiments are successful.
- determine the role of the main chronic inflammation susceptibility locus, i.e. the MHC, on the composition of the skin and gut microbiota.
More information
Max Planck Institute for Evolutionary Biology
[1] ]Identification of quantitative trait loci in experimental epidermolysis bullosa acquisita. Ludwig RJ, Müller S, Marques Ad, Recke A, Schmidt E, Zillikens D, Möller S, Ibrahim SM. J Invest Dermatol. 2012 May; 132(5):1409-15.
[2] Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Rausch P, Rehman A, Künzel S, Häsler R, Ott SJ, Schreiber S, Rosenstiel P, Franke A, Baines JF. Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19030-5.
[3] Identification of quantitative trait loci for murine autoimmune pancreatitis. Asghari F, Fitzner B, Holzhüter SA, Nizze H, de Castro Marques A, Müller S, Möller S, Ibrahim SM, Jaster R. J Med Genet. 2011 Aug;48(8):557-62.