Microbiota, Mitochondria and Complex Diseases
Prof. Saleh Ibrahim, MD, recently Joined SIMR-College of Medicine and holds the position of professor in Immunology/Genetics
Joint appointment: University of Luebeck, Germany
Complex diseases, e.g. Autoimmune diseases or Diabetes, are thought to be caused by a complex interacting network of genes, environmental agents and their products. Nuclear genome variants predisposing to those diseases have been well characterized. However, little is known about the contribution of the mitochondrial genome nor the interacting environmental agents to complex diseases. The seminar will address this topic, focusing primarily on the methods and animal models developed by the speaker’s research group. Microbiota will be used as an example of a relatively well characterized environmental agent.
Since finishing his medical training in Egypt, Dr. Ibrahim has been studying autoimmunity for the last 20 years. He started this research at the Department of Bacteriology and Immunology of the Helsinki University (Finland) with a doctoral thesis in immunology, studying the potential influence of bacterial surface proteins on the B cell repertoire. He then moved to the Department of Molecular Biology at Princeton University (USA), where he studied the genetic basis and molecular mechanisms of B cell tolerance and received his training in molecular genetics. In 1997 he moved to the Institute of Immunology, University of Rostock (Germany), where he established an independent research group studying the genetic basis of autoimmune diseases. There he also established a transgenic animal unit and developed novel experimental models, e.g. the mitochondrial mutant mice resource. In 2008 he moved to the University of Lübeck as a professor of genetics. Since then his group has focused on studying the role of mitochondrial genome and gene-microbiota interactions in the pathogenesis of autoimmune diseases. To this end he recruited large patient cohorts from Germany, Europe and the middle East. His group is also using mouse models to test new hypothesis, e.g. that host genome variation influence skin and gut microbiota composition and that this in turn influence disease susceptibility. The findings from the animal models are then examined in the corresponding human cohorts.
1. Hirose M, Schilf P, Gupta Y, Wright MN, Wright MN, Jöhren O, Wagner AE, Sina C, Ziegler A, RistowM, Ibrahim SM. Lifespan effects of mitochondrial mutations. Nature. 2016 Dec 14;540(7633):E13-E14.
2. Wang J, Kalyan S, Steck N, Turner LM, Harr B, Künzel S, Vallier M, Häsler R, Franke A, Oberg HH, Ibrahim SM, Grassl GA, Kabelitz D, Baines JF. Analysis of intestinal microbiota in hybrid house mice reveals evolutionary divergence in a vertebrate hologenome. Nat Commun. 2015 Mar 4;6:6440. doi: 10.1038/ncomms7440.
3. Weiss H, Wester-Rosenloef L, Koch C, Koch F, Baltrusch S, Tiedge M, Ibrahim S. The mitochondrial Atp8 mutation induces mitochondrial ROS generation, secretory dysfunction, and β-cell mass adaptation in conplastic B6-mtFVB mice. Endocrinology. 2012 Oct;153(10):4666-76.
4. Srinivas G, Möller S, Wang J, Künzel S, Zillikens D, Baines JF, Ibrahim SM. Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering. Nat Commun, 2013; mDOI: 10.1038/ncomms3462
5. Yu X, Gimsa U, Wester-Rosenlöf L, Kanitz E, Otten W, Kunz M, Ibrahim SM. Dissecting the effects of mtDNA variations on complex traits using mouse conplastic strains. 2009 Genome Res. 19:159-165.