Within a large international collaborative study, lead by Norbert Hübner (Max-Delbrück-Centrum für Molekulare Medizin (MDC) in Berlin-Buch, Germany) and Stuart Cook (Imperial College London, UK), European scientists have now identified a gene network modulating type 1 diabetes risk. Furthermore, the scientists identified a key receptor within this important genetic framework.
The current multidimenstional approach was based on genetic as well as gene expression data in different species and provided new insights in respect that the innate viral response pathway and immune cells called macrophages are also implicated in T1D.
Transcription factors play a major role in regulating gene expression by binding to specific target sequences close to the gene of interest. Importantly, a transcription factor often regulates not only one gene but whole gene networks. “In recent years a multiplicity of risk genes has been discovered which play an important role in the development of various diseases. Despite this, though, the molecular mechanism that influences the onset of the diseases has not yet been fully understood” explains a leader of this currently published study, Prof. Dr. Norbert Huebner. “We have identified a transcription factor which controls a gene network in which a well known Diabetes mellitus Type 1 risk gene occurs.
“Further analysis of the data”, concluded Prof. Huebner, “revealed that the IDIN (interferon regulatory factor 7 (IRF71)-driven inflammatory network ) gene essentially influences Diabetes mellitus type 1 risk via the receptor EBI2 which regulates IDIN and thus plays a role in the development of this autoimmune disease. Additionally we were able to show the involvement of macrophages in the pathogenesis as well as able to show that similar signaling pathways are involved in Diabetes mellitus type 1 and Epstein Barr virus infection.”
More broadly, the study is of interest because it successfully combines gene networks and DNA sequence variation to emphasize the fact that regulatory regions that perturb biological networks can have an important role in disease risk.
“The present study is an extraordinary example of combining different genetic approaches, involving genome wide expression data from rats and humans as well as genome wide association data resulting in new and exciting insights into disease pathogenesis” explained Prof. Dr. Heribert Schunkert, coordinator of Cardiogenics. “In addition, it is a success story based on international collaboration between working groups and consortia with very different expertise” adds Prof. Dr. Jeanette Erdmann, scientific project manager of Cardiogenics.
The Cardiogenics consortium (www.cardiogenics.eu) has played its role in this work bringing experimental monocyte and macrophage expression data and expertise from its own focus on the assessment of heart attack risk to aid understanding of another important common disease. This EU project has gathered together leading research groups from six countries (Germany, United Kingdom, France, The Netherlands, Sweden, and Italy) to build a multi-disciplinary team to meet the challenge of improving cardiovascular healthcare. In addition to clinical teams, the consortium consists of academic groups specialized in human genetics, genetic epidemiology, bioinformatics, transcriptomics, and proteomics. In addition, the consortium has been supported by the Welcome Trust Sanger Institute, Europe's premier genome centre.A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
M. Heinig*, E. Petretto*, C. Wallace, L. Bottolo, M. Rotival, H. Lu, Y. Li, R. Sarwar, S.R. Langley, A. Bauerfeind, O. Hummel, Y.-A. Lee, S. Paskas, C. Rintisch, K. Saar, .J Cooper, R. Buchan, E.E. Gray, J.G. Cyster, Cardiogenics Consortium, J. Erdmann, C. Hengstenberg, S. Maouche, W.H. Ouwehand, C.M. Rice, N.J. Samani, H. Schunkert, A.H. Goodall, H. Schulz, H. Roider, M. Vingron, S. Blankenberg, T. Münzel, T. Zeller, S. Szymczak, A. Ziegler, L. Tiret, D.J. Smyth, M. Pravenec, T.J. Aitman, F. Cambien, D. Clayton, J.A. Todd, N. Hubner* und S.A. Cook* (*contributed equally)
Nature advance online publication 08.09.2010: http://www.nature.com/Contact
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy