Delgado de la Herran, H.C., Cheng, Y., and Perocchi, F.
Cell Calcium, 2021, 95, 102364.
Towards a systems-level understanding of mitochondrial biology
Human mitochondria are complex and highly dynamic biological systems, comprised of over a thousand parts and evolved to fully integrate into the specialized intracellular signaling networks and metabolic requirements of each cell and organ. Over the last two decades, several complementary, top-down computational and experimental approaches have been developed to identify, characterize and modulate the human mitochondrial system, demonstrating the power of integrating classical reductionist and discovery-driven analyses in order to de-orphanize hitherto unknown molecular components of mitochondrial machineries and pathways. To this goal, systematic, multiomics-based surveys of proteome composition, protein networks, and phenotype-to-pathway associations at the tissue, cell and organellar level have been largely exploited to predict the full complement of mitochondrial proteins and their functional interactions, therefore catalyzing data-driven hypotheses. Collectively, these multidisciplinary and integrative research approaches hold the potential to propel our understanding of mitochondrial biology and provide a systems-level framework to unraveling mitochondria-mediated and disease-spanning pathomechanisms.
Being constantly flooded by a mass of stimuli, it is impossible for us to react to all of them. The same holds true for a little fish. Which stimuli should it pay attention to and which not? Scientists at the Max Planck Institute of Neurobiology have now deciphered the neuronal circuit that zebrafish use to prioritize visual stimuli. Surrounded by predators, a fish can thus choose its escape route from this predicament.
Even though we are not exposed to predators, we still have to decide which stimuli we pay attention to – for example, when crossing a street. Which cars should we avoid, which ones can we ignore? "The processes in the brain and the circuits that lead to this so-called selective attention are largely unexplored," explains Miguel Fernandes, a postdoctoral researcher in Herwig Baier's department. "But if we understand this in a simple animal model like the zebrafish, it can give us fundamental insights into decision-making mechanisms in humans." For this reason, Miguel Fernandes and his colleagues studied the behavior of zebrafish in the predicament described above: Using virtual reality, the team simulated two predators approaching a fish from the left and right at the same speed. In most cases, the fish focused on one of the two predators and fled in the opposite direction. They thus integrated only one, the so-called "winner stimulus", into their escape route (winner-take-all strategy).
Behrens, A., Rodschinka, G., and Nedialkova, D.D.
(IMPRS-LS students in bold)
Mol Cell, 2021, online ahead of print.
High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by mim-tRNAseq
Measurements of cellular tRNA abundance are hampered by pervasive blocks to cDNA synthesis at modified nucleosides and the extensive similarity among tRNA genes. We overcome these limitations with modification-induced misincorporation tRNA sequencing (mim-tRNAseq), which combines a workflow for full-length cDNA library construction from endogenously modified tRNA with a comprehensive and user-friendly computational analysis toolkit. Our method accurately captures tRNA abundance and modification status in yeast, fly, and human cells and is applicable to any organism with a known genome. We applied mim-tRNAseq to discover a dramatic heterogeneity of tRNA isodecoder pools among diverse human cell lines and a surprising interdependence of modifications at distinct sites within the same tRNA transcript.
Researchers at the Max Planck Institute (MPI) of Biochemistry have developed a method to quantify transfer RNAs and study their modifications in cells from diverse organisms
Transfer RNAs (tRNAs) deliver specific amino acids to ribosomes during translation of messenger RNA into proteins. The abundance of tRNAs can therefore have a profound impact on cell physiology, but measuring the amount of each tRNA in cells has been limited by technical challenges. Researchers at the MPI of Biochemistry have now overcome these limitations with mim-tRNAseq, a method that can be used to quantify tRNAs in any organism and will help improve our understanding of tRNA regulation in health and disease.
A cell contains several hundred thousand tRNA molecules, each of which consists of only 70 to 90 nucleotides folded into a cloverleaf-like pattern. At one end, tRNAs carry one of the twenty amino acids that serve as protein building blocks, while the opposite end pairs with the codon specifying this amino acid in messenger RNA during translation. Although there are only 61 codons for the twenty amino acids, cells from different organisms can contain hundreds of unique tRNA molecules, some of which differ from each other by only a single nucleotide. Many nucleotides in tRNAs are also decorated with chemical modifications, which help tRNAs fold or bind the correct codon.
Retinal ganglion cells (RGCs) are the bottleneck through which all visual impressions flow from the retina to the brain. A team from the Max Planck Institute of Neurobiology, University of California Berkeley and Harvard University created a molecular catalog that describes the different types of these neurons. In this way, individual RGC types could be systematically studied and linked to a specific connection, function and behavioral response.
When zebrafish see light, they often swim towards it. Same with prey, although the signals are entirely different. A predator, on the other hand, prompts the fish to escape. That’s good, because a mix-up would have fatal consequences. But how does the brain manage to react to a visual stimulus with the proper behavior?
Optical signals are generated by photons that bombard the retina of the eye. Neurons in the retina collect and process these impressions. While doing so, the retina focuses on the important details: Is there contrast or color? Are there small or large objects? Is something moving? Once these details are filtered out, retinal ganglion cells (RGCs) send them to the brain, where they are translated into a specific behavior.
As the only connection between the retina and the brain, RGCs play a central role in the visual system. We already knew that specific RGC types sends different details to different regions of the brain. However, it has been unclear how RGC types differ on the molecular level, what their respective functions are, and how they help to regulate context-dependent behavior.
Klein, A.S., and Gogolla, N.
Science, 2021, 371, 122-123.
How mice feel each other's pain or fear
Empathic behaviors play crucial roles in human society by regulating social interactions, promoting cooperation toward a common goal, and providing the basis for moral decision-making (1, 2). Understanding the neural basis of empathy is crucial to understanding not only the human mind but also the neural mechanisms that give rise to social behaviors and the principles of our societies. Functional imaging studies in humans have identified essential brain regions that are engaged when people empathize with the affective experiences of others. However, human neuroimaging studies provide only limited spatial resolution and are solely correlative in nature. It has thus remained unclear how empathy with distinct affective experiences is set apart within the brain. read more