Scientists watch live brain cell circuits spark and fire EurekAlert (press release) Article: Cao et al. "Genetically targeted optical electrophysiology in intact neural circuits," Cell, August 8, 2013, DOI: 10.1016/j.cell.2013.07.027.
spectroscopyNOW.com Seeing clearly: X-rays help spectroscopyNOW.com It is, after all, also linked directly to the function of many other ion channels involved in the contractions of the heart and other muscles and in nerve signalling.
What is the origin of life on Earth? What is the future of life in the age of synthetic biology? These are two of the biggest questions of contemporary biology, and the questions that drive Adam Rutherford’s new book, Creation: How Science is Reinventing Life Itself, a compelling and accessible two-part look through the history and future of living cells. Through chapters that span the early history of microscopy to recent debates on the regulation of biotechnology and genomics, Rutherford tells the complicated story of the science of life as it might have been and as it might be.
By simulating 25,000 generations of evolution within computers, Cornell University engineering and robotics researchers have discovered why biological networks tend to be organized as modules -- a finding that will lead to a deeper understanding of the evolution of complexity.
The new insight also will help evolve artificial intelligence, so robot brains can acquire the grace and cunning of animals.
From brains to gene regulatory networks, many biological entities are organized into modules -- dense clusters of interconnected parts within a complex network. For decades biologists have wanted to know why humans, bacteria and other organisms evolved in a modular fashion. Like engineers, nature builds things modularly by building and combining distinct parts, but that does not explain how such modularity evolved in the first place. Renowned biologists Richard Dawkins, Günter P. Wagner, and the late Stephen Jay
Gould identified the question of modularity as central to the debate over "the evolution of complexity."
For years, the prevailing assumption was simply that modules evolved because entities that were modular could respond to change more quickly, and therefore had an adaptive advantage over their non-modular competitors. But that may not be enough to explain the origin of the phenomena.
The team discovered that evolution produces modules not because they produce more adaptable designs, but because modular designs have fewer and shorter network connections, which are costly to build and maintain. As it turned out, it was enough to include a "cost of wiring" to make evolution favor modular architectures.
Cooperation in animals and humans is widely observed even if evolutionary biology theories predict the evolution of selfish individuals. Previous game theory models have shown that cooperation can evolve when the game takes place in a structured population such as a social network because it limits interactions between individuals. Modularity, the natural division of a network into groups, is a key characteristic of all social networks but the influence of this crucial social feature on the evolution of cooperation has never been investigated. Here, we provide novel pieces of evidence that network modularity promotes the evolution of cooperation in 2-person prisoner's dilemma games. By simulating games on social networks of different structures, we show that modularity shapes interactions between individuals favouring the evolution of cooperation. Modularity provides a simple mechanism for the evolution of cooperation without having to invoke complicated mechanisms such as reputation or punishment, or requiring genetic similarity among individuals. Thus, cooperation can evolve over wider social contexts than previously reported.
Network modularity promotes cooperation Marianne Marcoux, David Lusseau
Journal of Theoretical Biology Volume 324, 7 May 2013, Pages 103–108
A long sought structure that validates the results of our recent study published in JBC ( Stabilization of the conductive conformation of a Kv channel: The lid mechanism. Santos JS, Syeda R, Montal M. J Biol Chem. 2013 Apr 22. [Epub ahead of print]).
Voltage-gated ion channels are important determinants of cellular excitability. The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) and KV7 (M-) channels are voltage-gated ion channels. Both channels are activated at sub-threshold potentials and have biophysical properties that mirror each other. KV7 channels inhibit neuronal excitability. Thus, mutations in KV7 channels that are associated with Benign Familial Neonatal Convulsions (BFNC) are likely to be epileptogenic. Mutations in HCN channels have also been associated with idiopathic epilepsies such as GEFS+. In addition, HCN channel expression and function are modulated during symptomatic epilepsies such as temporal lobe epilepsy. It is, though, unclear as to whether the changes in HCN channel expression and function associated with the various forms of epilepsy promote epileptogenesis or are adaptive. In this review, we discuss this as well as the potential for KV7 and HCN channels as drug targets for the treatment of epilepsy. (...) - by Shah MM et al., Neuropharmacology, Volume 69, June 2013, Pages 75–81
X-ray crystallography has been the gold standard for obtaining atomically precise structures for proteins and other nanostructures, but this method requires substantial amounts of crystalline material, and not all proteins, and ...
Jose Santos's insight:
this is new, creative, and promissing research in structural biology...finally!
The first cell may have originated in a salty soup in which large biomolecules cluster spontaneously to form a protocell. A paper in PNAS (Enhanced transcription rates in membrane-free protocells formed by coacervation or cell lysate) discusses implications for building a synthetic cell.
The system that Daniel and colleagues have assembled takes bacterial cells and transforms them into living calculators that can compute logarithms, multiplication, division, and can perform even more sophisticated functions such as acting as an in vivo pH meter… with three or fewer genetic parts. Furthermore, because their system operates in the analog signal processing domain, it can process graded information, characteristic of the natural environment in which we live and with which we interact. Such analog computation could permit the design of cellular sensors for pathogens or toxins.
(Phys.org) —Photographers rely on precision lenses to generate well-focused and crystal-clear images. These high-quality optics—readily available and produced in huge quantities—are often taken for granted.But as scientists explore the details of materials spanning just billionths of a meter, engineering the nanoscale equivalent of a camera lens becomes notoriously difficult.
Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These host-defense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics.
by Chen Songa, Conrad Weichbrodt, Evgeniy S. Salnikov, Marek Dynowski, Björn O. Forsberg, Burkhard Bechinger, Claudia Steinem, Bert L. de Groot, Ulrich Zachariae and Kornelius Zeth
Science Editor's Choice comment:
Antimicrobial peptides (AMPs) provide an important first-line defense against bacteria and fungi in multicellular organisms. They do so by targeting the microbial cell membrane, but their precise mechanisms of action are not well understood. Song et al. used a combination of x-ray crystallography, electrophysiology, and molecular dynamics simulations to better understand the mechanism of one such AMP: dermcidin (DCD). DCD is secreted into human sweat and found on the skin. It is active against a range of bacteria, including methicillin-resistant Staphylococcus aureus and Mycobacterium tuberculosis. The authors' analysis revealed that DCD forms a hexameric barrel-like channel of elongated α helices in bacterial membranes. Stabilization of the channel required the presence of zinc. The channel formed was highly permeable to water and ions and so was a major membrane disruptor. This ability to disrupt the transmembrane potential of bacterial cell membranes can lead to rapid cell death and thus provide protective antimicrobial activity to the host.
The miniaturization of electronics continues to create unprecedented capabilities in computer and communications applications, enabling handheld wireless devices with tremendous computing performance operating on battery power.
A team of researchers at Columbia Engineering has used miniaturized electronics to measure the activity of individual ion-channel proteins with temporal resolution as fine as one microsecond, producing the fastest recordings of single ion channels ever performed. Ion channels are biomolecules that allow charged atoms to flow in and out of cells, and they are an important work-horse in cell signaling, sensing, and energetics.
They are also being explored for nanopore sequencing applications. As the "transistors" of living systems, they are the target of many drugs, and the ability to perform such fast measurements of these proteins will lead to new understanding of their functions. The researchers have designed a custom integrated circuit to perform these measurements, in which an artificial cell membrane and ion channel are attached directly to the surface of the amplifier chip.
"Scientists have been measuring single ion channels using large rack-mount electronic systems for the last 30 years," says Jacob Rosenstein, the lead author on the paper. Rosenstein was a PhD student in electrical engineering at the School at the time this work was done, and is now an assistant professor at Brown University. "By designing a custom microelectronic amplifier and tightly integrating the ion channel directly onto the amplifier chip surface, we are able to reduce stray capacitances that get in the way of making fast measurements."
"This work builds on other efforts in my laboratory to study the properties of individual molecules using custom electronics designed for this purpose," says Ken Shepard, professor of electrical engineering at the School and Rosenstein's adviser. The Shepard group continues to find ways to speed up these single-molecule measurements. "In some cases," he adds, "we may be able to speed things up to be a million times faster than current techniques."