The week’s most astounding developments from the neobiological frontier.

August 4, 2022

First “wiring” diagram of the human immune system

The activation, control, and dynamic interactions of cells all over the human body via surface proteins is what connects all the different cells in our immune system and allows us to mount systemic defenses against microbes and other health threats. But how do all these cells talk to each other? Researchers at the Wellcome Sanger Institute in Cambridge and the University of York in the United Kingdom have used a high-throughput surface receptor screening method to answer that question, systematically mapping most of the protein-protein interactions on human leukocytes—a major cellular component of the immune system also known as white blood cells. The result shows a “high-confidence and quantitative view of the receptor wiring that connects human immune cells,” they write, which could “finally begin to disentangle cellular circuits in immunity and beyond.” Nature

Probiotics: colonizing hostile guts with local guides

Despite the promise of probiotics, one of its challenges is that when you feed someone transplanted or engineered microbes, the bacteria often fail to colonize the gut. The luminal (interior) environment of the intestines is teeming with microbes and hostile even to “good” bacteria. So they pass right through, diminishing their therapeutic properties. Now a team of gastroenterologists from the University of California, San Diego, has found a clever way around this pickle by taking bacteria straight from the gut to use as the basis of live bacterial therapeutics. As a proof-of-principle, they isolated existing Escherichia coli samples from stool cultures of normal mice and modified these bacteria to express functional genes. When they reintroduced the E. coli back into the mice, the modified bacteria achieved perpetual engraftment, induced physiological changes, and improved pathologies like glucose tolerance in obese mice. Cell

An oral phage therapy for gut microbiome

In a completely different approach to treating diseases linked to the gut microbiome, researchers at the Weizmann Institute of Science in Rehovot, Israel, have demonstrated they could knock down disease-related “bad” bacteria in the gut using a combination of five specially designed bacteriophage viruses. They looked at the gut microbiomes of 537 people suffering from inflammatory bowel disease who live in France, Israel, Germany, and the United States and identified a type of bacteria called Klebsiella pneumoniae strongly associated with the disease. Introducing the same strains into mice gave the rodents flare ups, so they designed a way to suppress the bacteria with the phages. As a proof-of-concept, they showed that the phage combination reduced inflammation in the colons of mice, and then conducted a phase 1 trial with 18 people, showing that a swallowed phage combination therapy persisted in the GI tract and was well tolerated in the volunteer subjects. Cell

Environment trumps genetics in psychotic episodes

We are always amazed by twin studies. What better way to tease apart genetic risk factors from epigenetics and other environmental impacts on human health than to compare sets of two people separated by a common zygote. In the latest twin study, researchers at Birkbeck University of London looked at 4,855 pairs of 16-year-old twins in the United Kingdom from 2014–2020 and another 6,435 twin pairs from Sweden and found that environmental factors play a greater role in psychotic experiences among adolescents, like hallucinations and paranoia, than do genetic factors—especially when these young people are exposed to known environmental risk factors like bullying, smoking, cannabis use, or low birth weight. JAMA Psychiatry

Mice that grow rat sperm

Researchers at ETH Zurich in Switzerland have used a technique called blastocyst complementation to generate rat sperm cells inside sterile mice. “Our study shows that we can use sterile animals as hosts for the generation of germ cells from other animal species,” says stem cell biologist Ori Bar-Nur, a senior author of the study. The technique may be useful for producing transgenic animals or assisting in the preservation of endangered species, the researchers write. Stem Cell Reports

Immunofluorescence staining of a mouse-rat chimera testis tissue shows the successful restoration of the male sperm in sterile mice. The microscope cryosection shows the spermatid and sperm markers VASA (red) and PNA (green). Joel Zvick/ETH Zurich

Itch-specific neurons discovered in China

Just as we were doing final edits on our story this week about the future of itch drugs, we found a paper addressing a fundamental mystery involving the neurophysiology of itchiness. Researchers at the Army Medical University in Chongqing, China, have discovered itch-specific neurons in the ventrolateral orbital cortex of the brain. These neurons are distinct from the brain’s pain-related neurons, which provides a resounding answer to the long-standing question of whether or not there are specific neurons inside the brain that modulate itch, according to the researchers. Science

Machine makes dead pig organs viable

A team of researchers at Yale University has demonstrated a new organ perfusion system called OrganEx that can halt cellular death and restore some of the molecular and cellular functions to pig tissues, even when initiated one hour after the animal’s death. A jumbled network of pumps, tubes, heaters, filters, and sensors, the instrument does not restore normal activity to the tissues or reanimate the animals, but it has the potential to keep organs alive longer after death. If translated to humans, this could increase the availability of deceased donor organs for transplantation and improve our understanding of resuscitation science and what happens to the body when we die. Nature