More than 1 million people are affected by inflammatory bowel disease in North America alone and direct healthcare expenses for inflammatory bowel disease in the United States are estimated at more than $15 billion annually. What the scientists have been able to do is construct a set of mathematical equations that describe the movement of different cells in the immune system and how these cells interact with different bacteria that can trigger disease in the colon.
Said Josep Bassaganya-Riera, associate professor at VBI, "In collaboration with the Network Dynamics and Simulation Science Laboratory at VBI, researchers in the Nutritional Immunology and Molecular Medicine group have developed a model of inflammation that allows us to investigate in silico the immunological changes that occur when inflammatory bowel disease takes hold of otherwise healthy gastrointestinal tissue."
Inflammatory bowel disease starts when the gut initiates an abnormal immune response to some of the one hundred trillion or so bacteria that come into contact with the colon of the human body. In some cases, this response can lead to inflammatory lesions and ulcerations in the cells lining the colon through which bacteria can invade the tissue. This invasion can lead to recurring inflammation, diarrhea, rectal bleeding, and malnutrition, the tell-tale symptoms of inflammatory bowel disease and infections with some gastroenteric pathogens.
Said Stephen Eubank, deputy director of the Network Dynamics and Simulation Science Laboratory at VBI and one of the authors on the paper, "One thing we are trying to understand with this research is how your immune system lives in peace with the commensal, peace-loving bacteria, yet can still mount a rapid, controlled defense against unfriendly bacteria. We are also interested in what happens when parts of the immune system do not behave as expected, for example when otherwise friendly immune cells attack healthy tissue." Remarked Eubank: "The computational model described in this paper allows scientists to examine these types of events in considerable detail but we are already working on a next-generation model that will allow us to take an even bigger step. Our goal is to develop an agent-based model in a petascale computing environment that will be able to represent hundreds of millions of cells involved in this type of immune response."
Previous studies have shown that in healthy individuals the detrimental immune response is avoided by the presence of regulatory immune cells that inhibit the inflammatory pathway. Added Bassaganya-Riera, "Our model allows researchers to identify those components of the inflammatory pathway that allow regulatory mechanisms to be overridden and immune-mediated disease to proceed."
The mathematical and computational approach of the scientists has already revealed one of the weak links in the complex network of interactions. Said Katherine Wendelsdorf, a graduate student in the Network Dynamics and Simulation Science Laboratory at VBI and lead author of the paper, "Our math analyses revealed a specific type of immune cell, a pro-inflammatory macrophage, to be one of the main culprits for unregulated inflammation in inflammatory bowel disease."
When conditions were simulated in which M1 or classically activated macrophages were removed from the site of infection, a drastic decrease in the inflammatory response linked to disease was observed in the simulations. This observation suggests that M1 macrophages are key targets for intervention strategies to fight mucosal inflammation.
Said Bassaganya-Riera, "Modeling approaches cannot replace experimentation but they can provide a framework for organizing existing data, generating novel mechanistic hypotheses and deciding where to focus key validation experiments. Future efforts in our group will focus on modeling immunity to enteric pathogens."
The research was funded by the National Institutes of Health (MIDAS project grants 5U01 GM070694-05 and 2U01 GM070694-7).
† Wendelsdorf K, Bassaganya-Riera J, Hontecillas R, Eubank S (2010) Model of colonic inflammation: Immune modulatory mechanisms in inflammatory bowel disease Journal of Theoretical Biology 264(4): 1225-1239.
The Virginia Bioinformatics Institute (http://www.vbi.vt.edu) at Virginia Tech is a premier bioinformatics, computational biology, and systems biology research facility that uses transdisciplinary approaches to science combining information technology, biology, and medicine. These approaches are used to interpret and apply vast amounts of biological data generated from basic research to some of today's key challenges in the biomedical, environmental, and agricultural sciences. With more than 240 highly trained multidisciplinary, international personnel, research at the institute involves collaboration in diverse disciplines such as mathematics, computer science, biology, plant pathology, biochemistry, systems biology, statistics, economics, synthetic biology, and medicine. The large amounts of data generated by this approach are analyzed and interpreted to create new knowledge that is disseminated to the world's scientific, governmental, and wider communities.
Barry Whyte | EurekAlert!
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