Article by Lalita Panicker, Consulting Editor, Views and Editor, Insight, Hindustan Times, New Delhi
Blood is red because it’s brimming with the oxygen-toting protein haemoglobin, but scientists have long wondered whether cells outside of the bloodstream depend on this protein as well. Now, a team of researchers from China has demonstrated that cartilage-making cells called chondrocytes manufacture and use haemoglobin, perhaps to help them survive in cartilage’s oxygen-poor environment. https://www.science.org/content/article/more-red-blood-cells-depend-hemoglobin-surprising-study-cartilage-reveals?
The results surprised bone researchers, but they give the study high marks. The authors “provide solid and convincing evidence that chondrocytes can produce haemoglobin and that it has a physiological role,” says bone developmental biologist Ernestina Schipani of the University of Pennsylvania Perelman Medical School, who wasn’t connected to the research.
Red blood cells are about 95% haemoglobin, which makes sense because their main job is to ferry the oxygen that sustains the body’s tissues. Researchers have detected haemoglobin in an assortment of other cell types, including neurons, lung cells, and immune cells called macrophages, but so far they haven’t found conclusive evidence that the protein performs a vital role for these cells.
Scientists had not previously reported finding haemoglobin in chondrocytes. In 2017, however, pathologist Feng Zhang of the Fourth Military Medical University was studying bone development in young mice when he noticed some unusual blobs in chondrocytes from the animals’ growth plates, the cartilaginous layers near the ends of some bones that allow them to lengthen. Not only did the structures resemble red blood cells, but they were also rich in haemoglobin. Zhang joined forces with cell biologist Qiang Sun of the Chinese Academy of Medical Sciences and other researchers to better understand what these mysterious objects were and what they were doing in the animals’ cartilage.
Oxygen is scarce in the growth plates, which don’t have their own blood supply. Yet chondrocytes divide rapidly, indicating they must have mechanisms to function amid low oxygen levels. The researchers wondered whether haemoglobin helped chondrocytes survive. To test that hypothesis, the scientists turned to genetically altered mice that produce fewer functional haemoglobin molecules than normal. Analysing the animals’ cartilage, they found that large numbers of chondrocytes perished in the growth plates.
Next, the scientists repeated the experiment in rodents with reduced amounts of haemoglobin only in their chondrocytes. Once again, the cells died in droves in the growth plates, the researchers revealed earlier this month in Nature.
To probe how haemoglobin might protect chondrocytes, the team grew unaltered and genetically modified growth plate cells in a low-oxygen environment. Unlike haemoglobin-depleted cells, normal chondrocytes readily released oxygen under these conditions, and they were less likely to die, the scientists determined.
The scientists think the haemoglobin-containing blobs they identified in the growth plates function as oxygen depots for chondrocytes, absorbing the scarce molecule from their surroundings and then releasing it to meet cells’ needs. If so, they would represent the second adaptation that enables chondrocytes to withstand low oxygen levels. Researchers had previously found another mechanism that activates an alternative metabolic pathway for breaking down sugars that doesn’t require oxygen.
Like youth, growth plates are fleeting. In humans, they form before birth and disappear around puberty. But chondrocytes persist throughout life elsewhere in the body, including in the joints, where they help maintain the cartilage. These cells, too, are remote from the blood supply and have to survive oxygen scarcity. The team has found the haemoglobin harbouring structures in chondrocytes from other parts of mice’s bodies, including the ribs and feet, as well as in human knee cartilage.
Still unknown is whether haemoglobin enables chondrocytes in these locations to survive oxygen scarcity like it does in growth plates. The work also raises the possibility that a shortfall of haemoglobin in chondrocytes contributes to conditions in which bone growth is impaired, such as certain types of dwarfism, Ono says. “This [paper] opens up the opportunity for many other studies.”
/////
Bluetongue virus is spreading rapidly among livestock in the Netherlands, killing sheep and sickening cattle. The virus, which is spread by midges, does not infect humans, but concern is high because Dutch farms have been stricken with a strain for which no vaccine is commercially available in Europe. https://www.science.org/content/article/news-glance-endangered-plants-diversity-clinical-trials-and-testing-fusion-reactor?
In the past 2 weeks, the number of Dutch farms with infections rose from about 300 to more than 1100; a sheep in Belgium tested positive last week. A previous outbreak, which spread across Europe in 2007, cost an estimated €175 million in the Netherlands alone. Its agriculture ministry is considering using a live virus vaccine from South Africa.
////
John-Arne Røttingen, a prominent public health official, diplomat, and medical scientist, has been appointed as the new head of the Wellcome Trust, the U.K. foundation announced today. Røttingen, who was the founding CEO of the Coalition for Epidemic Preparedness Innovations (CEPI) and has been ambassador for global health at the Ministry of Foreign Affairs in his native Norway since 2020, will take up the influential role in 2024. https://www.science.org/content/article/norwegian-global-health-expert-john-arne-rottingen-named-wellcome-trust-ceo?
He will be just the sixth person in the past 50 years to run the research charity, which was established in 1936 with funds bequeathed in the will of Henry Wellcome, co-founder of the pharmaceutical company Burroughs Wellcome & Company, to advance medical research.
Røttingen will take the reins from Paul Schreier, who has been interim CEO since earlier this year, after Jeremy Farrar stepped down to become chief scientist at the World Health Organization (WHO). Farrar offered his approval of Wellcome’s decision today, calling it an “outstanding choice.”
Wellcome is one of the largest nongovernmental funders of scientific research in the world. In his new role, Røttingen will help oversee the spending of £16 billion (more than $19 billion) over the next decade to find “science-based solutions” to challenges such as mental health, infectious disease, and the health impacts of climate change, the foundation said in a press release.
Alongside a research career spanning medicine and epidemiology, Røttingen has held numerous roles in public health and administration. As CEO of CEPI, which was launched in collaboration with Wellcome in 2017, Røttingen worked to obtain funding for the development of vaccines to target global health challenges including Middle East respiratory syndrome, coronavirus, and Lassa virus. During the COVID-19 pandemic, he led the steering committee of WHO’s Solidarity Trial, which evaluated the efficacy of various medications in treating SARS-CoV-2 infection.
Røttingen is also known for his advocacy for open-access publishing: As chief executive of the Research Council of Norway, he co-led a task force with other national funding agencies to push for full and open access to research publications through a project known as Plan S. He holds an M.D. and Ph.D. from the University of Oslo, a Master of Science from the University of Oxford, and a Master of Public Administration from Harvard University.
Røttingen tells Science it will be a “great honour” to lead Wellcome. One of his priorities will be to ensure that health solutions identified by Wellcome-funded research actually make their way into policy. He also emphasises the importance of funding high-risk research alongside safer projects—a balance that can be hard to achieve for any research funder, he says.
////
For three decades, Helen Sang has tinkered with the genomes of chickens to try to make the birds resistant to the flu viruses that periodically devastate flocks and raise fears of a human pandemic. Now, as an especially virulent strain of avian influenza sweeps through poultry and wild birds around the world, the geneticist at the University of Edinburgh’s Roslin Institute has her first solid success. Using the CRISPR gene editor and recent findings about what makes poultry vulnerable to flu, Sang and colleagues from three other institutions have created chickens that can resist real-life doses of avian flu viruses. “Sticking to it gets you somewhere in the end,” she says. https://www.science.org/content/article/proof-concept-crispr-engineered-chickens-shrug-flu?
The result, published last week in Nature Communications, is “a long-awaited achievement,” says Jiří Hejnar, a virologist at the Czech Academy of Sciences’s Institute of Molecular Genetics whose group showed in 2020 that CRISPR-edited chickens could resist a cancer-causing virus. But farmers won’t be raising flu-proof chickens anytime soon. The edited birds still became infected when exposed to larger amounts of the flu virus. And the strategy raises a safety concern: chickens edited this way could, in theory, drive the evolution of flu variants better at infecting people. “What this showed is a proof of concept,” says Wendy Barclay, a virologist at Imperial College London who worked on the new study. “But we’re not there yet.”
/////
More than 3,000 cell types — many of them new to science — have been revealed in the largest-ever atlas of human neurons and other brain cells. One team that contributed to the huge project, which involved hundreds of scientists, sequenced the RNA of more than three million cells. Another uncovered links between certain types of brain cell and neuropsychiatric disorders. “This is only the beginning,” says molecular biologist Bing Ren.
Nature | 5 min read
Reference: 21 papers in Science, Science Advances and Science Translational Medicine
