Karolinska Institutet shows why natural killer cells react to COVID-19

 

Little has been known to date about how the immune system’s natural killer (NK) cells detect which cells have been infected with SARS-CoV-2. An international team of scientists led by researchers from Karolinska Institutet, ranked amongst the world's best medical schools, in Sweden now shows that NK cells respond to a certain peptide on the surface of infected cells. The study, which is published in Cell Reports, is an important piece of the puzzle in our understanding of how the immune system reacts to COVID-19.

NK cells are white blood cells that are part of the innate immune system. Unlike cells in the adaptive immune defense, they can recognize and kill cancer cells and virus-infected cells immediately without having encountered them before. This ability is controlled by a balance between the NK cells’ activating and inhibiting receptors, which can react to different molecules on the surface of other cells. NK cells are part of the innate immune system. Image: NIAID

The virus is revealed by a peptide

A new study shows why certain NK cells are activated when encountering a cell infected with SARS-CoV-2. The infected cells contain a peptide from the virus that triggers a reaction in NK cells that carry a particular receptor, NKG2A, able to detect the peptide.

“Our study shows that SARS-CoV-2 contains a peptide that is displayed by molecules on the cell surface,” says Quirin Hammer, a researcher at the Center for Infectious Medicine (CIM), Karolinska Institutet. “The activation of NK cells is a complex reaction, and here the peptide blocks the inhibition of the NK cells, which allows them to be activated. This new knowledge is an important piece of the puzzle in our understanding of how our immune system reacts in the presence of this viral infection.”

The study was a major collaboration between Karolinska Institutet, Karolinska University Hospital, and research laboratories and universities in Italy, Germany, Norway, and the USA. The first phase was to test their hypothesis using supercomputer simulations that were then confirmed in the laboratory. The decisive phase was the infection of human lung cells with SARS-CoV-2 in a controlled environment, whereupon the researchers could show that NK cells with the receptor in question are activated to a greater degree than the NK cells without it.

Monitoring new virus variants

“These findings are important to our understanding of how immune cells recognize cells infected with SARS-CoV-2,” says Dr. Hammer. “This may become significant when monitoring new virus variants to determine how well the immune system responds to them.”

The study is now being followed up with the help of a biobank at Karolinska University Hospital and Karolinska Institutet containing blood samples from over 300 people treated for COVID-19 during the first wave of the pandemic.

“We’ll be examining if the composition of NK cells a person has contributes to how severe their symptoms are when infected with SARS-CoV-2,” he continues.

UK builds a new sea ice fragmentation module to help improve climate model predictions

ARCTIC sea ice is an important indicator of climate change and its rapid decline in past decades has been a wake-up call to scientists, policy-makers, and the general public.  Arctic sea-ice in summer

Now, an innovative new project featuring Dr. Byongjun (Phil) Hwang from the University of Huddersfield’s School of Applied Sciences will determine the role of sea ice fragmentation in the accelerated retreat of the Arctic ice-cap by combining new and emerging observations, new theory and process modeling. 

The research is being funded by the National Environment Research Council (NERC) as part of a responsive project award titled ‘Fragmentation and Melt of Arctic Sea-Ice’.

Climate model accuracy 

The latest assessment from the Intergovernmental Panel on Climate Change (IPCC) concluded that it was likely that the Arctic would become reliably ice-free by 2050 assuming greenhouse gas emissions continue to increase. However, the climate simulations used by the IPCC often fail to realistically capture large-scale properties of the Arctic sea ice, such as the extent, variability, and recent trends which can lead to the impairment of climate model accuracy. 

“This is why it is imperative we improve simulations of Arctic sea ice so we can provide a better understanding of the recent observed changes and deliver credible projections of the future,” said Dr. Hwang, who is Director of the University's Centre for Climate Resilient Societies.

“By building a fundamental understanding of sea ice fragmentation we will improve climate model predictions. This will help assess risks and opportunities as well as inform important policy decisions about adaptation and mitigation.”

The three-year project, which is being led by Professor Danny Feltham at the University of Reading, will result in a new sea ice fragmentation module delivered to climate and weather modeling groups including the Met Office, the National Oceanography Centre, the British Antarctic Survey, and the European Centre for Medium-Range Weather Forecasts.

As a geophysicist and remote sensing expert, Korean-born Dr. Hwang has developed a specialism in the dynamics and thermodynamics of snow and sea ice in polar regions.  He has undertaken a large number of expeditions to the Arctic, including some tough mid-winter assignments.

A seasoned Arctic researcher, Dr. Hwang has already made 15 voyages to the region, observing, recording, and analyzing seasonal changes in the ice. The data he has gathered on Arctic sea ice retreat has been an important contribution to the scientific debate about climate change.

Japanese built network models may help us understand the spread of new variants in a pandemic

New simulation shows how infectivity of new variants affects spread

Researchers from Tokyo Metropolitan University have performed numerical simulations based on network theory which show how numbers of infections in a pandemic change when a new variant emerges. They found a non-linear dependence between how infectious the new variant is compared to the existing one, an effect not seen in previous work. Their model may be applied to understand real pandemics such as COVID-19 and inform control measures. Simulation on a network of numbers of susceptible (S), infected (I) and recovered (R) from a pandemic and its variant (I’, R’) over time. At t=21, a variant was added.

Ever since it began to spread in late 2019, COVID-19 has had a devastating impact on people’s lives. With wave after wave of new variants continuing to wreak havoc around the world, scientists have been looking for ways to understand how the disease spreads. In particular, there is the issue of how new variants appear, spread, and end up displacing the existing strain. Understanding the dynamics of variants in a population is vital to controlling their spread.

A classic framework for modeling pandemic dynamics is the “compartmental” SIR model, looking at the numbers of susceptible (S), infected (I), and recovered (R) members of a population. The numbers are related by equations and solved, giving many of the salient features of how a disease spreads; the pandemic spreads rapidly before slowing down as the number of susceptible cases decreases and more patients recover. However, the model cannot account for the varied nature of the population i.e. a given infected individual does not have an equal probability of infecting all others, and the number of contacts that people have can vary greatly from one person to another. Any model that tries to capture pandemic dynamics and get to grips with where and how it spreads needs to use a more sophisticated model.

That’s why Emeritus Professor Yutaka Okabe and Professor Akira Shudo from Tokyo Metropolitan University have turned to network theory, a mathematical framework that can capture how different members of a population connect to others. Using different types of networks, they were able to create a more realistic model for how an infectious disease might spread. Key features included dynamic absorbing states, states in which the network can get stuck in overtime e.g. a state with no infected people. With a few infections and low infectivity, the network would collapse back to the infection-free state. Contrary to conventional models, the number of individuals who experienced infection does not scale linearly with how much more infectious a variant is compared to the existing strain.

The team performed a numerical simulation of the microscopic model on the network; in the middle of a simulation of infectious disease, they added a variant that is more transmissible than the original strain.  Looking at the numbers, the team found that a variant with the same infectivity as the existing strain fails to take off at all. This is a direct result of the non-linear nature of the simulation, as the network collapses back to an absorbing state with no infections. As the infectivity of the new variant is ramped up, the population becomes more likely to become infected with the variant as opposed to the existing strain, increasing the rate for the new strain at the expense of the old one. The non-linear nature of how the infection numbers increase with the variant infectivity is a product of the microscopic nature of the network model, giving a more detailed, nuanced picture than before.

The team hopes that their model may be utilized to form effective strategies to contain infectious diseases, looking at points of significant connectivity in the network and understanding how their isolation affects overall infections. As the COVID-19 pandemic continues to rage, fundamental studies of how diseases spread are a vital piece in informed decision-making aimed at bringing normal life back to society.

A milestone for MilkyWay@home - Measuring dark matter in a tidal stream of stars

Prof.Heidi Jo Newberg explains how the MilkyWay@home volunteer supercomputer was used to determine the shape and dark matter content of the ultrafaint dwarf galaxy that fell into the Milky Way three billion years ago and was ripped apart to form the Orphan-Chenab Stream (OCS).The measured dark matter mass is ten times less than that of dwarf galaxies observed today.This could mean that ultrafai...
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Ancient dwarf galaxy reconstructed with MilkyWay@home supercomputing

Astrophysicists for the first time have calculated the original mass and size of a dwarf galaxy that was shredded in a collision with the Milky Way billions of years ago. Reconstructing the original dwarf galaxy, whose stars today thread through the Milky Way in a stellar “tidal stream,” will help scientists understand how galaxies like the Milky Way formed, and could aid in the search for dark matter in our galaxy. H.NewbergAPJ2 22 1dc39

“We’ve been running simulations that take this big stream of stars, back it up for a couple of billion years, and see what it looked like before it fell into the Milky Way,” said Heidi Newberg, a professor of physics, astrophysics, and astronomy at Rensselaer Polytechnic Institute. “Now we have a measurement from data, and it’s the first big step toward using the information to find dark matter in the Milky Way.”

Billions of years ago, the dwarf galaxy and others like it near the Milky Way were pulled into the larger galaxy. As each dwarf galaxy coalesced with the Milky Way, its stars were pulled by “tidal forces,” the same kind of differential forces that make tides on Earth. The tidal forces distorted and eventually ripped the dwarf galaxy apart, stretching its stars into a tidal stream flung across the Milky Way. Such tidal mergers are fairly common, and Newberg estimates that “immigrant” stars absorbed into the Milky Way make up most of the stars in the galactic halo, a roughly spherical cloud of stars that surrounds the spiral arms of the central disk.

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Critically, the position and velocities of the tidal stream stars carry information about the Milky Way’s gravitational field.

Reconstructing the dwarf galaxy is a research task that combines data from star surveys, physics, and Newberg’s MilkyWay@Home distributed supercomputer, which harnesses 1.5 petaflops –a measure of computer processing speed– of home computer power donated by volunteers. This large amount of processing power makes it possible to simulate the destruction of a large number of dwarf galaxies with different shapes and sizes and identify a model that best matches the tidal stream of stars that we see today.

“It’s an enormous problem, and we solve it by running tens of thousands of different simulations until we get one that actually matches. And that takes a lot of computer power, which we get with the help of volunteers all over the world who are part of MilkyWay@Home,” Newberg said, “We’re brute-forcing it, but given how complicated the problem is, I think this method has a lot of merits.”

As published today in The Astrophysical Journal, Newberg’s team estimates the total mass of the original galaxy whose stars today form the Orphan-Chenab Stream as 2x107 times the mass of our sun.

However, only a little more than 1% of that mass is estimated to be made up of ordinary matter like stars. The remainder is assumed to be a hypothetical substance called dark matter that exerts a gravitational force, but that we cannot see because it does not absorb or give off light. The existence of dark matter would explain a discrepancy between the gravitational pull of the mass of the matter we can see, and the far larger pull needed to account for the formation and movement of galaxies. The gravitational pull from dark matter is estimated to make up as much as 85% of the matter in the universe, and tidal streams of stars that fell in with dwarf galaxies could be used to determine where dark matter is located in our galaxy.

“Tidal stream stars are the only stars in our galaxy for which it is possible to know their positions in the past,” Dr. Newberg said. “By looking at the current speeds of stars along a tidal stream, and knowing they all used to be in about the same place and moving at the same speed, we can figure out how much the gravity changes along that stream. And that will tell us where the dark matter is in the Milky Way.”

The research also finds that the progenitor of the Orphan-Chenab stream has less mass than the galaxies measured in the outskirts of our galaxy today, and if this small mass is confirmed it could change our understanding of how small stellar systems form and then merge to make larger galaxies like our Milky Way.

Dr. Newberg, an expert in the galactic halo, is a pioneer in identifying stellar tidal streams in the Milky Way. One day, she hopes that MilkyWay@home will help her measure more than the properties of one disintegrated dwarf galaxy. Ideally, she would like to simultaneously fit many dwarf galaxies, their orbits, and the properties of the Milky Way galaxy itself. This goal is complicated by the fact that the properties of our galaxy change over the billions of years that it takes for a small galaxy to fall in and be ripped apart to make these tidal streams.

“By painstakingly tracking the path of stars pulled into the Milky Way, Dr. Newberg and her team are building an image that shows us not just a dwarf galaxy long-since destroyed, but also sheds light on the formation of our galaxy and the very nature of matter,” said Curt Breneman, dean of the Rensselaer School of Science.

At Rensselaer, Newberg was joined in the research by Eric J. Mendelsohn, Siddhartha Shelton, Jeffery M. Thompson. Carl J. Grillmair at the California Institute of Technology, and Lawrence M. Widrow at Queen’s University, also contributed to the finding. “Estimate of the Mass and Radial Profile of the Orphan-Chenab Stream’s Dwarf Galaxy Progenitor Using MilkyWay@home” was published with support from the National Science Foundation, and with data from the Sloan Digital Sky Survey, the Dark Energy Camera at the Cerro Tololo Inter-American Observatory, and the National Aeronautics and Space Administration/Infrared Processing & Analysis Center Infrared Science Archive.