Whither systems biology

Cell biologists are interested in how complexity arises from the interaction of different molecules. However, cells are many orders of magnitude larger than the protein-binding interfaces. To bridge these vast difference in scales, biologists construct hierarchies of organization of cellular structures. I describe how systems biology provides an approach to bridge these different scales

MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders

Understanding complex diseases such as sporadic Alzheimer disease (AD) has been a major challenge. Unlike the familial forms of AD, the genetic and environmental risks factors identified for sporadic AD are extensive. MicroRNAs are one of the major noncoding RNAs that function as negative regulators to silence or suppress gene expression via translational inhibition or message degradation. Their discovery has evoked great excitement in biomedical research for their promise as potential disease biomarkers and therapeutic targets. Key microRNAs have been identified as essential for a variety of cellular events including cell lineage determination, proliferation, apoptosis, DNA repair, and cytoskeletal organization; most, if not all, acting to fine-tune gene expression at the post-transcriptional level in a host of cellular signaling networks. Dysfunctional microRNA-mediated regulation has been implicated in the pathogenesis of many disease states. Here, the current understanding of the role of miRNAs in the central nervous system is reviewed with emphasis on their impact on the etiopathogenesis of sporadic AD

Membrane invaginations reveal cortical sites that pull on mitotic spindles in one-cell C. elegans embryos.

Asymmetric positioning of the mitotic spindle in C. elegans embryos is mediated by force-generating complexes that are anchored at the plasma membrane and that pull on microtubules growing out from the spindle poles. Although asymmetric distribution of the force generators is thought to underlie asymmetric positioning of the spindle, the number and location of the force generators has not been well defined. In particular, it has not been possible to visualize individual force generating events at the cortex. We discovered that perturbation of the acto-myosin cortex leads to the formation of long membrane invaginations that are pulled from the plasma membrane toward the spindle poles. Several lines of evidence show that the invaginations, which also occur in unperturbed embryos though at lower frequency, are pulled by the same force generators responsible for spindle positioning. Thus, the invaginations serve as a tool to localize the sites of force generation at the cortex and allow us to estimate a lower limit on the number of cortical force generators within the cell

Straight GDP-Tubulin Protofilaments Form in the Presence of Taxol

International audienceMicrotubules exist in dynamic equilibrium, growing and shrinking by the addition or loss of tubulin dimers from the ends of protofilaments. The hydrolysis of GTP in b-tubulin destabilizes the microtubule lattice by increasing the curvature of protofilaments in the microtubule and putting strain on the lattice. The ob- servation that protofilament curvature depends on GTP hydrolysis suggests that microtubule destabil- izers and stabilizers work by modulating the curvature of the microtubule lattice itself. Indeed, the microtu- bule destabilizer MCAK has been shown to increase the curvature of protofilaments during depolymeriza- tion. Here, we show that the atomic force microscopy (AFM) of individual tubulin protofilaments provides sufficient resolution to allow the imaging of single pro- tofilaments in their native environment. By using this assay, we confirm previous results for the effects of GTP hydrolysis and MCAK on the conformation of pro- tofilaments. We go on to show that taxol stabilizes microtubules by straightening the GDP protofilament and slowing down the transition of protofilaments from straight to a curved configuration

Actively Contracting Bundles of Polar Filaments

We introduce a phenomenological model to study the properties of bundles of polar filaments which interact via active elements. The stability of the homogeneous state, the attractors of the dynamics in the unstable regime and the tensile stress generated in the bundle are discussed. We find that the interaction of parallel filaments can induce unstable behavior and is responsible for active contraction and tension in the bundle. Interaction between antiparallel filaments leads to filament sorting. Our model could apply to simple contractile structures in cells such as stress fibers.Comment: 4 pages, 4 figures, RevTex, to appear in Phys. Rev. Let

Challenging the orthodoxy: union learning representatives as organic intellectuals

Teacher education and continuing professional development have become a key areas of controversy in England since the period of school sector restructuring following the 1988 Education Reform Act. More recently teacher training and professional development have often been used to promote and reinforce a narrow focus on the government’s ‘standards agenda’. However, the emerging discourse of ‘new professionalism’ has raised the profile of professional development in schools, and together with union learning representatives, there are opportunities to secure real improvements in teachers’ access to continuing professional development. This paper argues however that union learning representatives must go beyond advocating for better access to professional development and should raise more fundamental questions about the nature of professional development and the education system it serves. Drawing on Gramsci’s notion of the ‘organic intellectual’, the paper argues that union learning representatives have a key role as organisers of ideas – creating spaces in which the ideological dominance of current policy orthodoxy might be challenged

The mitotic spindle in the one-cell C. elegans embryo is positioned with high precision and stability

Precise positioning of the mitotic spindle is important for specifying the plane of cell division, which in turn determines how the cytoplasmic contents are partitioned into the daughter cells, and how the daughters are positioned within the tissue. During metaphase in the early C. elegans embryo, the spindle is aligned and centered on the anterior-posterior axis by a microtubule-dependent machinery that exerts restoring forces when the spindle is displaced from the center. To investigate the accuracy and stability of centering, we tracked the position and orientation of the mitotic spindle during the first cell division with high temporal and spatial resolution. We found that the precision is remarkably high: the cell-to-cell variation in the transverse position of the center of the spindle during metaphase, as measured by the standard deviation, was only 1.5% of the length of the short axis of the cell. Spindle position is also very stable: the standard deviation of the fluctuations in transverse spindle position during metaphase was only 0.5% of the short axis of the cell. Assuming that stability is limited by fluctuations in the number of independent motor elements such as microtubules or dyneins underlying the centering machinery, we infer that the number is on the order of one thousand, consistent with the several thousand of astral microtubules in these cells. Astral microtubules grow out from the two spindle poles, make contact with the cell cortex, and then shrink back shortly thereafter. The high stability of centering can be accounted for quantitatively if, while making contact with the cortex, the astral microtubules buckle as they exert compressive, pushing forces. We thus propose that the large number of microtubules in the asters provides a highly precise mechanism for positioning the spindle during metaphase while assembly is completed prior to the onset of anaphase.Comment: Accepted in Biophysical Journal (2016