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Primeur weekly 2019-12-02

Exascale supercomputing

LUMI supercomputer will arrive soon - CSC signed the Hosting Agreement with EuroHPC ...

The way is open to building world-class supercomputers in Europe ...

Crowd computing

Crowdsourced 'supercomputer' enables more localised and accurate rainfall forecasts ...

Quantum computing

Researchers reach milestone in quantum standardization ...

Ultrafast quantum simulations: A new twist to an old approach ...

Middleware

OpenNebula 5.10 "Boomerang" released ...

Hardware

Boston to continue HPC Roadshow in South Africa at the CHPC Conference ...

Fujitsu begins shipping supercomputer Fugaku ...

KISTI collaborates with Rescale to diversify R&D service of KISTI-5 supercomputer, Nurion ...

Applications

Rethinking brain-inspired computing from the atom up ...

Toward more efficient computing, with magnetic waves ...

A new theory for how black holes and neutron stars shine bright ...

Molecular eraser enables better data storage and computers for AI ...

Argonne and TAE Technologies heating up plasma energy research ...

IBM makes higher quality weather forecasts available worldwide ...

How the immune system gets on the wrong track ...

Pervasive Technology Institute and Cancer Computer join forces for cure ...

TOP500

CNES's Data Processing Centre increases capacity and reaches 15th place in IO500 world ranking ...

WekaIO places first on IO-500 Challenge ...

The Cloud

NetApp and Google Cloud advance strategic partnership to drive innovation in the Cloud ...

USFlash

Atos grows Santos Dumont supercomputer capacity fivefold making it largest in Latin America ...

How the immune system gets on the wrong track


How the mutation stabilizes the SDHA-SDHB interactions: molecular representation of the mutated SDHA (green) and the SDHB (blue) complex, shown in ribbons. A typical interaction between the mutated residue (Thr45) and adjacent residues in SDHA is highlighted (sticks). Carbon, oxygen, nitrogen and hydrogen atoms are coloured black, red, blue and grey. Image: Olivier Bignucolo.
26 Nov 2019 Lugano - With the help of simulations on the supercomputer "Piz Daint", an international research team has succeeded in making inflammation-promoting molecular processes in special cells visible. This research enables more targeted treatments for certain immune disorders and the production of drugs with fewer side effects.

The intact human immune system works as precise as a clockwork: it repels infections and cancer cells without harming the otherwise healthy organism. But if the immune system is not intact, those affected are usually dependent on medical help. Many patients with genetically-caused primary immunodeficiency disorders (PIDs) suffer from a lack of antibodies (primary antibody deficiency), which are normally produced in so-called B cells. As a result, they are susceptible to infections, but also to autoimmune and auto-inflammatory diseases. Recently, an international team of researchers has succeeded in deciphering an essential molecular process in the B cells of a subgroup of affected patients - thus enabling tailored and more efficient treatment.

The researchers, led by Christoph Hess and Mike Recher, both professors at the Department of Biomedicine of the University of Basel and the University Hospital of Basel as well as at the University of Cambridge, have taken a close look at the cellular metabolism of B cells in PID. They found that in these patients, the power plants of the cell - the so-called mitochondria - exhibit increased cellular respiration. In the affected patients, researchers also found a mutation in the germ line of the protein SDHA, which is a key component of the respiratory chain of the cell.

Co-author Olivier Bignucolo from the University of Lausanne used the Swiss National Supercomputing Centre (CSCS) supercomputer "Piz Daint" to visualize the molecular dynamics of SDHA in these cells. Olivier Bignucolo is first assistant at the Department of Pharmacology and Toxicology and a computational structural biologist specialized in molecular dynamic simulations. Using "Piz Daint" and a special software, Olivier Bignucolo attempted to clarify the cause of the increased cellular respiration in the B cells from these patients. "Molecular dynamic simulations complement conventional imaging techniques perfectly, as they enable the analysis of the biological system over time at the atomic level", Olivier Bignucolo noted. "The behaviour of ions, water and any ligand are assessed together with the proteins of interest." Using simulations, the researchers were able to describe a modified network of atomic interactions caused by SDHA mutations.

The simulations showed that the mutation of the protein SDHA enhances its interaction with SDHB, thus augmenting the activity of the respiratory chain and driving accumulation of a certain salt (fumarate), which in turn activates a signalling cascade leading to the production of so-called cytokines which ultimately cause inflammatory reactions. On the basis of these results, the researchers were able to treat one patient with an antibody to specifically block a key inflammation mediator (cytokine) triggered by the increased interaction of the two proteins SDHA and SDHB. This treatment reduced systematic inflammation and the patient's condition improved, according to the scientists. "The decoding of such processes not only clarifies basic biological mechanisms, but also enables more targeted treatments or the production of drugs with fewer side effects", emphasised the physician Christoph Hess.

Burgener A. et al. are the authors of the paper titled " SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2 ", published inNature Immunology20, 1311–1321 (2019) - doi:10.1038/s41590-019-0482-2.

The video highlights the interaction between SDHB (blue) and SDHA (green): on the right hand the wild type, left the mutated SDHA. The coloured spheres representing the interacting atoms: carbon, oxygen and nitrogen. The interactions between the mutated variant of SDHA and SDHB left lasts significantly longer.
Source: Swiss National Supercomputing Centre - CSCS

Back to Table of contents

Primeur weekly 2019-12-02

Exascale supercomputing

LUMI supercomputer will arrive soon - CSC signed the Hosting Agreement with EuroHPC ...

The way is open to building world-class supercomputers in Europe ...

Crowd computing

Crowdsourced 'supercomputer' enables more localised and accurate rainfall forecasts ...

Quantum computing

Researchers reach milestone in quantum standardization ...

Ultrafast quantum simulations: A new twist to an old approach ...

Middleware

OpenNebula 5.10 "Boomerang" released ...

Hardware

Boston to continue HPC Roadshow in South Africa at the CHPC Conference ...

Fujitsu begins shipping supercomputer Fugaku ...

KISTI collaborates with Rescale to diversify R&D service of KISTI-5 supercomputer, Nurion ...

Applications

Rethinking brain-inspired computing from the atom up ...

Toward more efficient computing, with magnetic waves ...

A new theory for how black holes and neutron stars shine bright ...

Molecular eraser enables better data storage and computers for AI ...

Argonne and TAE Technologies heating up plasma energy research ...

IBM makes higher quality weather forecasts available worldwide ...

How the immune system gets on the wrong track ...

Pervasive Technology Institute and Cancer Computer join forces for cure ...

TOP500

CNES's Data Processing Centre increases capacity and reaches 15th place in IO500 world ranking ...

WekaIO places first on IO-500 Challenge ...

The Cloud

NetApp and Google Cloud advance strategic partnership to drive innovation in the Cloud ...

USFlash

Atos grows Santos Dumont supercomputer capacity fivefold making it largest in Latin America ...