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Essays in Biochemistry

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https://www.readbyqxmd.com/read/30429283/bridging-centrioles-and-pcm-in-proper-space-and-time
#1
REVIEW
Ramya Varadarajan, Nasser M Rusan
Throughout biology, specifying cellular events at the correct location and time is necessary for ensuring proper function. The formation of robust microtubule organizing centers (MTOCs) in mitosis is one such event that must be restricted in space to centrosomes to prevent ectopic MTOC formation elsewhere in the cell, a situation that can result in multipolar spindle formation and aneuploidy. The process of reaching maximum centrosome MTOC activity in late G2, known as centrosome maturation, ensures accurate timing of nuclear envelope breakdown and proper chromosome attachment...
November 14, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30429282/tapping-into-the-treasures-of-tubulin-using-novel-protein-production-methods
#2
REVIEW
Nuo Yu, Niels Galjart
Microtubules are cytoskeletal elements with important cellular functions, whose dynamic behaviour and properties are in part regulated by microtubule-associated proteins (MAPs). The building block of microtubules is tubulin, a heterodimer of α- and β-tubulin subunits. Longitudinal interactions between tubulin dimers facilitate a head-to-tail arrangement of dimers into protofilaments, while lateral interactions allow the formation of a hollow microtubule tube that mostly contains 13 protofilaments. Highly homologous α- and β-tubulin isotypes exist, which are encoded by multi-gene families...
November 14, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30429281/context-dependent-spindle-pole-focusing
#3
REVIEW
Lori Borgal, James G Wakefield
The formation of a robust, bi-polar spindle apparatus, capable of accurate chromosome segregation, is a complex process requiring the co-ordinated nucleation, sorting, stabilization and organization of microtubules (MTs). Work over the last 25 years has identified protein complexes that act as functional modules to nucleate spindle MTs at distinct cellular sites such as centrosomes, kinetochores, chromatin and pre-existing MTs themselves. There is clear evidence that the extent to which these different MT nucleating pathways contribute to spindle mass both during mitosis and meiosis differs not only between organisms, but also in different cell types within an organism...
November 14, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315097/microtubule-nucleation-by-%C3%AE-tubulin-complexes-and-beyond
#4
REVIEW
Corinne A Tovey, Paul T Conduit
In this short review, we give an overview of microtubule nucleation within cells. It is nearly 30 years since the discovery of γ-tubulin, a member of the tubulin superfamily essential for proper microtubule nucleation in all eukaryotes. γ-tubulin associates with other proteins to form multiprotein γ-tubulin ring complexes (γ-TuRCs) that template and catalyse the otherwise kinetically unfavourable assembly of microtubule filaments. These filaments can be dynamic or stable and they perform diverse functions, such as chromosome separation during mitosis and intracellular transport in neurons...
October 12, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315096/microtubule-structure-by-cryo-em-snapshots-of-dynamic-instability
#5
REVIEW
Szymon W Manka, Carolyn A Moores
The development of cryo-electron microscopy (cryo-EM) allowed microtubules to be captured in their solution-like state, enabling decades of insight into their dynamic mechanisms and interactions with binding partners. Cryo-EM micrographs provide 2D visualization of microtubules, and these 2D images can also be used to reconstruct the 3D structure of the polymer and any associated binding partners. In this way, the binding sites for numerous components of the microtubule cytoskeleton-including motor domains from many kinesin motors, and the microtubule-binding domains of dynein motors and an expanding collection of microtubule associated proteins-have been determined...
October 12, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30287587/measuring-microtubule-dynamics
#6
REVIEW
Alexander James Zwetsloot, Gokhan Tut, Anne Straube
Microtubules are key players in cellular self-organization, acting as structural scaffolds, cellular highways, force generators and signalling platforms. Microtubules are polar filaments that undergo dynamic instability, i.e. transition between phases of growth and shrinkage. This allows microtubules to explore the inner space of the cell, generate pushing and pulling forces and remodel themselves into arrays with different geometry and function such as the mitotic spindle. To do this, eukaryotic cells employ an arsenal of regulatory proteins to control microtubule dynamics spatially and temporally...
October 4, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30287585/trafficking-of-ciliary-membrane-proteins-by-the-intraflagellar-transport-bbsome-machinery
#7
REVIEW
Jenna L Wingfield, Karl-Ferdinand Lechtreck, Esben Lorentzen
Bardet-Biedl syndrome (BBS) is a rare inherited disease caused by defects in the BBSome, an octameric complex of BBS proteins. The BBSome is conserved in most organisms with cilia, which are microtubule (MT)-based cell organelles that protrude from the cell surface and function in motility and sensing. Cilia assembly, maintenance, and function require intraflagellar transport (IFT), a bidirectional motility of multi-megadalton IFT trains propelled by molecular motors along the ciliary MTs. IFT has been shown to transport structural proteins, including tubulin, into growing cilia...
October 4, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30366988/integrative-workflows-for-network-analysis
#8
REVIEW
Faiz M Khan, Shailendra K Gupta, Olaf Wolkenhauer
Due to genetic heterogeneity across patients, the identification of effective disease signatures and therapeutic targets is challenging. Addressing this challenge, we have previously developed a network-based approach, which integrates heterogeneous sources of biological information to identify disease specific core-regulatory networks. In particular, our workflow uses a multi-objective optimization function to calculate a ranking score for network components (e.g. feedback/feedforward loops) based on network properties, biomedical and high-throughput expression data...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30366987/systems-biology-old-news-or-new-stimulus-for-biochemistry
#9
EDITORIAL
Walter Kolch, Dirk Fey, Colm J Ryan
In this issue of Essays in Biochemistry , biochemistry meets systems biology-a blind date that may hold all the promises, pitfalls and failures of a relationship where a new discipline has been sprung upon a well-established one. As the articles in this issue show, the blind date in this case has great potential to develop into a long-term relationship, where both partners share common values but can benefit from different complementary approaches. Together this partnership is well poised to address and solve some of the major challenges in modern biology...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315099/studying-how-genetic-variants-affect-mechanism-in-biological-systems
#10
REVIEW
Francesco Raimondi, Robert B Russell
Genetic variants are currently a major component of system-wide investigations into biological function or disease. Approaches to select variants (often out of thousands of candidates) that are responsible for a particular phenomenon have many clinical applications and can help illuminate differences between individuals. Selecting meaningful variants is greatly aided by integration with information about molecular mechanism, whether known from protein structures or interactions or biological pathways. In this review we discuss the nature of genetic variants, and recent studies highlighting what is currently known about the relationship between genetic variation, biomolecular function, and disease...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315098/enzymatic-complexes-across-scales
#11
REVIEW
Panagiotis L Kastritis, Anne-Claude Gavin
An unprecedented opportunity to integrate ~100 years of meticulous in vitro biomolecular research is currently provided in the light of recent advances in methods to visualize closer-to-native architectures of biomolecular machines, and metabolic enzymes in particular. Traditional views of enzymes, namely biomolecular machines, only partially explain their role, organization and kinetics in the cellular milieu. Enzymes self- or hetero-associate, form fibers, may bind to membranes or cytoskeletal elements, have regulatory roles, associate into higher order assemblies (metabolons) or even actively participate in phase-separated membraneless organelles, and all the above in a transient, temporal and spatial manner in response to environmental changes or structural/functional changes of their assemblies...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315095/integrating-omics-data-into-genome-scale-metabolic-network-models-principles-and-challenges
#12
REVIEW
Charlotte Ramon, Mattia G Gollub, Jörg Stelling
At genome scale, it is not yet possible to devise detailed kinetic models for metabolism because data on the in vivo biochemistry are too sparse. Predictive large-scale models for metabolism most commonly use the constraint-based framework, in which network structures constrain possible metabolic phenotypes at steady state. However, these models commonly leave many possibilities open, making them less predictive than desired. With increasingly available -omics data, it is appealing to increase the predictive power of constraint-based models (CBMs) through data integration...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30315094/reverse-engineering-gene-regulatory-networks-by-modular-response-analysis-a-benchmark
#13
REVIEW
Bertram Klinger, Nils Blüthgen
Gene regulatory networks control the cellular phenotype by changing the RNA and protein composition. Despite its importance, the gene regulatory network in higher organisms is only partly mapped out. Here, we investigate the potential of reverse engineering methods to unravel the structure of these networks. Particularly, we focus on modular response analysis (MRA), a method that can disentangle networks from perturbation data. We benchmark a version of MRA that was previously successfully applied to reconstruct a signalling-driven genetic network, termed MLMSMRA, to test cases mimicking various aspects of gene regulatory networks...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30287586/systems-biology-primer-the-basic-methods-and-approaches
#14
REVIEW
Iman Tavassoly, Joseph Goldfarb, Ravi Iyengar
Systems biology is an integrative discipline connecting the molecular components within a single biological scale and also among different scales (e.g. cells, tissues and organ systems) to physiological functions and organismal phenotypes through quantitative reasoning, computational models and high-throughput experimental technologies. Systems biology uses a wide range of quantitative experimental and computational methodologies to decode information flow from genes, proteins and other subcellular components of signaling, regulatory and functional pathways to control cell, tissue, organ and organismal level functions...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30139878/experimental-and-engineering-approaches-to-intracellular-communication
#15
REVIEW
John G Albeck, Michael Pargett, Alexander E Davies
Communication between and within cells is essential for multicellular life. While intracellular signal transduction pathways are often specified in molecular terms, the information content they transmit remains poorly defined. Here, we review research efforts to merge biological experimentation with concepts of communication that emerge from the engineering disciplines of signal processing and control theory. We discuss the challenges of performing experiments that quantitate information transfer at the molecular level, and we highlight recent studies that have advanced toward a clearer definition of the information content carried by signaling molecules...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30139877/a-systems-perspective-of-heterocellular-signaling
#16
REVIEW
Alan Wells, H Steven Wiley
Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30072490/reconstructing-phosphorylation-signalling-networks-from-quantitative-phosphoproteomic-data
#17
REVIEW
Brandon M Invergo, Pedro Beltrao
Cascades of phosphorylation between protein kinases comprise a core mechanism in the integration and propagation of intracellular signals. Although we have accumulated a wealth of knowledge around some such pathways, this is subject to study biases and much remains to be uncovered. Phosphoproteomics, the identification and quantification of phosphorylated proteins on a proteomic scale, provides a high-throughput means of interrogating the state of intracellular phosphorylation, both at the pathway level and at the whole-cell level...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30072489/exploiting-vulnerabilities-in-cancer-signalling-networks-to-combat-targeted-therapy-resistance
#18
REVIEW
Peter T Harrison, Paul H Huang
Drug resistance remains one of the greatest challenges facing precision oncology today. Despite the vast array of resistance mechanisms that cancer cells employ to subvert the effects of targeted therapy, a deep understanding of cancer signalling networks has led to the development of novel strategies to tackle resistance both in the first-line and salvage therapy settings. In this review, we provide a brief overview of the major classes of resistance mechanisms to targeted therapy, including signalling reprogramming and tumour evolution; our discussion also focuses on the use of different forms of polytherapies (such as inhibitor combinations, multi-target kinase inhibitors and HSP90 inhibitors) as a means of combating resistance...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30072488/single-cell-protein-analysis-for-systems-biology
#19
REVIEW
Ezra Levy, Nikolai Slavov
The cellular abundance of proteins can vary even between isogenic single cells. This variability between single-cell protein levels can have regulatory roles, such as controlling cell fate during apoptosis induction or the proliferation/quiescence decision. Here, we review examples connecting protein levels and their dynamics in single cells to cellular functions. Such findings were made possible by the introduction of antibodies, and subsequently fluorescent proteins, for tracking protein levels in single cells...
October 26, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/30030366/neuroimaging-in-mitochondrial-disorders
#20
REVIEW
Mario Mascalchi, Martino Montomoli, Renzo Guerrini
MRI and 1 H magnetic resonance spectroscopy (1 HMRS) are the main neuroimaging methods to study mitochondrial diseases. MRI can demonstrate seven 'elementary' central nervous system (CNS) abnormalities in these disorders, including diffuse cerebellar atrophy, cerebral atrophy, symmetric signal changes in subcortical structures (basal ganglia, brainstem, cerebellum), asymmetric signal changes in the cerebral cortex and subcortical white matter, leukoencephalopathy, and symmetric signal changes in the optic nerve and the spinal cord...
July 20, 2018: Essays in Biochemistry
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