A single protein can turn on and off a key component of the immune system by changing partners in an elegant genomic dance, said researchers at the University of Southern California and Harvard Medical School.
Because autoimmune diseases – such as arthritis, allergies and dozens of other illnesses – begin when the body's defenses respond at the wrong time or place, the on-off mechanism for the immune system has been the subject of intense study for decades.
The USC-Harvard team studied proteins critical to immune tolerance, a term for the healthy balance between a weak immune system and an overly aggressive, indiscriminate watchdog.
Lin Chen, professor of molecular and computational biology at USC and lead co-author with Harvard's Anjana Rao, said the team's result would "open a big door for people to explain the fundamental mechanism of immune tolerance."
In the July 28 issue of Cell, the USC-Harvard group shows that the protein Nuclear Factor of Activated T cells (NFAT), in collaboration with FOXP3, an essential factor in regulatory T cells, orchestrates a genetic program critical to immune tolerance.
But the same NFAT, paired with a second family of proteins known as AP-1, instead stimulates immune response.
Chen said the finding offers the first strong evidence in favor of the 15-year-old "combinatorial control" theory of gene expression.
According to the theory, the specific expression of a gene depends on the combination of "transcription factors" acting on it. Transcription factors help to translate a gene's instructions into actual proteins. FOXP3 and NFAT are two such factors; the human body contains around 3,000.
"The work provides a structural demonstration of combinatorial control of gene expression," Chen said. "This is, in my view, the most direct demonstration that this is indeed happening in nature."
The researchers were able to identify single genes that were activated by NFAT in combination with AP-1 and suppressed by NFAT with FOXP3.
Beyond shedding light on the immune system, the Cell paper may advance biology and medicine toward a much larger goal: how to turn single genes on or off.
"This [result] has far-reaching implications for understanding the principles of signal transduction and transcriptional networks of living cells," Chen said.
The Cell paper, which Chen describes as spanning 14 years of laboratory work, builds on a result his group published in Nature in 1998.
Carl Marziali | 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