RESEARCH HIGHLIGHTS

Researchers shed new light on the journey of RNA out of the cell nucleus
 
In order for the cell to produce essential proteins, messages derived from DNA must somehow escape the nucleus in the form of RNA molecules. New work has determined the structure of one important component of the restrictive gate through which cargo, including genetic information in the form of RNA transcribed from DNA, must pass. More...
 
 
New method gives scientists a better look at how HIV infects and takes over its host cells
 
Viruses attack cells and commandeer their machinery in a complex and carefully orchestrated invasion. Scientists have long probed this process for insights into biology and disease, but essential details still remain out of reach. A new approach offers an unprecedented view of how HIV infects and appropriates a host cell, step by step. More...
 
 
The Trypanosome Nuclear Pore Reveals 1.5 Billion Years of Similarities and Differences
 
Given its functional importance, you might think that the nuclear pore complexes (NPCs) of all eukaryotes would be the same; that the constraints of natural selection might have prevented any variation from some successful early model. However, new research shows that the NPC of the parasite Trypanosoma brucei differs in some important ways from those of vertebrates, plants, and yeast. The findings shed light on the evolution of the NPC, strengthening the argument that it may have originated as a far simpler progenitor (Synopsis). More...
 
 
Study Reveals Architecture of the Molecular Machinery that Copies DNA
 
DNA replication is essential to all life, yet many basic mechanisms in that process remain unknown to scientists. The structure of the replisome, a block of proteins responsible for unwinding the DNA helix and then creating duplicate helices for cell division, is one such mystery. For the first time, researchers reveal the molecular architecture of this vital complex; and to their surprise, it does not look as they had expected. More...
 
 
New technique efficiently turns antibodies into highly tuned 'nanobodies'
 
Antibodies, in charge of recognizing and homing in on molecular targets, are among the most useful tools in biology and medicine. Nanobodies—antibodies' tiny cousins—can do the same tasks, and offer the tantalizing prospect of being much easier to produce. Unfortunately, their promise hasn't been fully realized because scientists have lacked an efficient way of identifying the nanobodies most closely tuned to their targets. A new techinique promises to make nanobodies dramatically more accessible for all kinds of research. More...
 
 
Method for identifying phosphorylated substrates of specific cyclin/cyclin-dependent kinase complexes
 
During proliferation, eukaryotic cells go through a defined series of phases. The primary regulators of this process are kinases paired with protein partners called cyclins. Exactly how these specific cyclin-kinase pairs orchestrate the myriad cellular events during each cell phase has been difficult to define largely because it has proven challenging to identify their substrates. Here, we describe a method to identify cyclin- and phase-specific substrates with high confidence and also to pinpoint their sites of modification. The method enabled us to identify the phosphatase Cdc14 as a substrate of a cyclin-kinase pair that acts during DNA synthesis in budding yeast and to uncover a new means by which this major antagonist of the cyclin-kinase pair is itself controlled. More...
 
 
Affinity proteomics catches elusive jumping genes in the act
 
LINE-1s are active human DNA parasites that are agents of genome dynamics in evolution and disease. These streamlined elements require host factors to complete their life cycles, whereas hosts have developed mechanisms to combat retrotransposition's mutagenic effects. As such, endogenous L1 expression levels are extremely low, creating a roadblock for detailed interactomic analyses. Here, we describe a system to express and purify highly active L1 RNP complexes from human suspension cell culture and characterize the copurified proteome. More...
 
 
Mass spectrometry identifies proteins present at tagged inhibitory synapses
 
Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD) exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain. More...
 
 
Structure-function mapping of a heptameric module in the nuclear pore complex
 
The structure of the yeast Nup84 complex deduced from EM and domain deletion mapping. More...
 
 
Scientists identify broad and potent HIV antibodies that mimic CD4 binding
 
A new approach gives researchers the ability to isolate single antibodies as well as investigate entire families of highly active antibodies against HIV. More...
 
 
A high-capacity ion trap (>106 ions) is coupled to a TOF mass spectrometer
 
A high-capacity ion trap coupled to a time-of-flight (TOF) mass spectrometer has been developed to carry out comprehensive linked scan analysis of all stored ions in the ion trap. The approach involves a novel tapered geometry high-capacity ion trap that can store more than 106 ions (range 800-4000 m/z) without degrading its performance. Ions are stored and scanned out from the high-capacity ion trap as a function of m/z, collisionally fragmented and analyzed by TOF. Please refer to the article or video for more information.
 
 
Webcasts of lab presentations at ASMS 2010
 
The presentations discuss lossless mass spectrometry, MRM interference, and replication fork dynamics. More...
 
 
Replication Fork Progression is Remarkably Uniform Throughout the Yeast Genome
 
Prior studies in budding yeast have led to a picture wherein the replication of DNA progresses at variable rates over different parts of the genome. Here, time-resolved ChIP-chip analysis and computer simulations lead to a new picture in which replication fork progression is remarkably uniform throughout the genome. More...
 
 
Research suggests core nuclear pore elements shared by all eukaryotes
 
About 1.7 billion years ago, the cell nucleus burst onto the scene, sequestering the cell's genetic material inside a protective inner membrane and setting the stage for the evolution of increasingly sophisticated creatures from yeast, say, to plants and human beings. Now research shows that one of the most basic design principles of this new eukaryotic life-form—the gatekeeper to the cell nucleus known as the nuclear pore complex—is largely shared across even the most distantly related eukaryotes. More...
 
 
New sequencing technique to prod medical benefits from killer venom
 
King Kong toxin, a component of the venom in some poisonous marine snails, has a peculiar power to go with its peculiar name. When injected into a meek little lobster in a tank full of superiors, the poison induces delusions of grandeur. More...
 
 
Researchers construct a device that mimics one of nature's key transport machines
 
A cell's nuclear pore complex controls transport of materials from one side to the other. Now, by trying to recreate the structure, scientists have gained a broader understanding of how it works. More...
 
 
The molecular architecture of the nuclear pore complex
 
Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the 456 constituent proteins of the NPC. More...