Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Conceptual barriers to understanding physical barriers Amulya Lingaraju, Tiha M. Long, Yitang Wang, Jotham R. Austin II, Jerrold R. Turner doi:10.1016/j.semcdb.2015.04.008 Seminars in Cell & Developmental Biology Volume 42, Pages 13–21 Claudins and Time, Space and the Vertebrate Body Axis
The members of the large family of claudin proteins regulate ion and water flux across the tight junction. claudins and other tight junction proteins can drive assembly and stabilization of a lipid-based strand structure.

Complex complexity.Dionisio_{September 16, 2015
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Assembly and function of claudins: Structure–function relationships based on homology models and crystal structures G. Krausea, J. Protzea, J. Piontek doi:10.1016/j.semcdb.2015.04.010 Seminars in Cell & Developmental Biology Volume 42, Pages 3–12 Claudins and Time, Space and the Vertebrate Body Axis
The tetra-span transmembrane proteins of the claudin family are critical components of formation and function of tight junctions (TJ). Detailed knowledge about structure–function relationships about claudins helps to reveal the molecular mechanisms of TJ assembly and regulation of paracellular permeability, which is yet not fully understood.

Work in progress... stay tuned. Complex complexity.Dionisio_{September 16, 2015
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Time, space and the vertebrate body axis A.J. Durston doi:10.1016/j.semcdb.2015.05.005 Seminars in Cell & Developmental Biology Volume 42, Pages 66–77 Claudins and Time, Space and the Vertebrate Body Axis
Anterior–posterior (A–P) patterning of the vertebrate main body axis regulated by timing. Anterior structures are specified early, posterior late. [...] integral BMP–anti BMP dependent A–P TST time–space translation (TST) mechanism

regulated by timing ? what regulates timing? Complex complexity.Dionisio_{September 16, 2015
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Temporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes Francesca B. Tuazon, Mary C. Mullins doi:10.1016/j.semcdb.2015.06.003 Seminars in Cell & Developmental Biology Volume 42, Pages 118–133 Claudins and Time, Space and the Vertebrate Body Axis
The vertebrate body plan is established through the precise spatiotemporal coordination of morphogen signaling pathways that pattern the anteroposterior (AP) and dorsoventral (DV) axes.

Complex complexity.Dionisio_{September 15, 2015
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The influence of transcription rates and delays in morphogen interpretation raises the question how these processes might be regulated at the molecular level.
Response to Nodal morphogen gradient is determined by the kinetics of target gene induction Julien Dubrulle, Benjamin M Jordan, Laila Akhmetova, Jeffrey A Farrell, Seok-Hyung Kim, Lilianna Solnica-Krezel, Alexander F Schier DOI: http://dx.doi.org/10.7554/eLife.05042 eLife 2015;4:e05042 http://elifesciences.org/content/4/e05042

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How a cell can tell where it is in a developing embryo has fascinated scientists for decades. A morphogen is released from a group of cells (called the ‘source’) and as it moves away its activity (called the ‘signal’) declines gradually. Cells sense this signal gradient and use it to detect their position with respect to the source. Nodal is an important morphogen and is required to establish the correct identity of cells in the embryo; for example, it helps determine which cells should become a brain or heart or gut cell and so on. [...] timing and transcription rate are important in determining the appropriate response to Nodal. Further work will be now needed to find out whether similar mechanisms regulate other processes that rely on the activity of morphogens.
Response to Nodal morphogen gradient is determined by the kinetics of target gene induction Julien Dubrulle, Benjamin M Jordan, Laila Akhmetova, Jeffrey A Farrell, Seok-Hyung Kim, Lilianna Solnica-Krezel, Alexander F Schier DOI: http://dx.doi.org/10.7554/eLife.05042 eLife 2015;4:e05042 http://elifesciences.org/content/4/e05042

Complex complexity.Dionisio_{September 15, 2015
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Response to Nodal morphogen gradient is determined by the kinetics of target gene induction Julien Dubrulle, Benjamin M Jordan, Laila Akhmetova, Jeffrey A Farrell, Seok-Hyung Kim, Lilianna Solnica-Krezel, Alexander F Schier DOI: http://dx.doi.org/10.7554/eLife.05042 eLife 2015;4:e05042 http://elifesciences.org/content/4/e05042
Morphogen gradients expose cells to different signal concentrations and induce target genes with different ranges of expression. morphogen interpretation is shaped by the kinetics of target gene induction: the higher the rate of transcription and the earlier the onset of induction, the greater the spatial range of expression.

Complex complexity.Dionisio_{September 15, 2015
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Three-Dimensional Gradients of Cytokine Signaling between T Cells Kevin Thurley , Daniel Gerecht , Elfriede Friedmann , Thomas Höfer PLOS •DOI: 10.1371/journal.pcbi.1004206 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004206
Immune responses are regulated by diffusible mediators, the cytokines, which act at sub-nanomolar concentrations. The spatial range of cytokine communication is a crucial, yet poorly understood, functional property. in a physiological setting, cytokine gradients between cells, and not bulk-phase concentrations, are crucial for cell-to-cell communication, emphasizing the need for spatially resolved data on cytokine signaling.

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Function does not follow form in gene regulatory circuits Joshua L. Payne & Andreas Wagner Scientific Reports 5, Article number: 13015 (2015) doi:10.1038/srep13015 http://www.nature.com/articles/srep13015
Gene regulatory circuits are to the cell what arithmetic logic units are to the chip: fundamental components of information processing that map an input onto an output. Gene regulatory circuits come in many different forms, distinct structural configurations that determine who regulates whom. [...] it is generally not possible to infer circuit function from circuit form, or vice versa. Gene expression is tightly regulated in both space and time. [...] complex circuit motifs are more functionally versatile than simple motifs [...] These findings highlight the limitations of diagrammatic representations of gene regulatory circuits, and underscore the importance of collecting detailed information about a circuit’s signal-integration logic. We are only beginning to understand how these various facets of promoter architecture affect gene expression. In gene regulatory circuits, function does not follow form, form rarely follows function, and form is severely constrained by multifunctionality.

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Oncology Meets Immunology: The Cancer-Immunity Cycle Daniel S. Chen, Ira Mellman doi:10.1016/j.immuni.2013.07.012 http://www.sciencedirect.com/science/article/pii/S1074761313002963
The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. [...] as complicated and incompletely understood human immunology may be, the immune response to cancer may be less complicated and less protean than the biology of cancer cells themselves.

Complex complexity. Encouraging news.Dionisio_{September 15, 2015
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Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases Dmitriy Gorenshteyn, Elena Zaslavsky, Miguel Fribourg, Christopher Y. Park, Aaron K. Wong, Alicja Tadych, Boris M. Hartmann, Randy A. Albrecht, Adolfo García-Sastre, Steven H. Kleinstein, Olga G. Troyanskaya DOI: http://dx.doi.org/10.1016/j.immuni.2015.08.014 http://www.cell.com/immunity/fulltext/S1074-7613(15)00346-5
ImmuNet and its associated analysis tools publicly available for the immune research community through an intuitive user-interactive website at http://immunet.princeton.edu/.

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Big Data Now Has a More Comprehensive Immune System http://www.clinicalomics.com/#big+data+now+has+a+more+comprehensive+immune+systemDionisio_{September 15, 2015
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The Big Data Addiction—NGS Has It Bad Greatest Challenge Lies In Effective Analysis and Interpretation Jeffrey S. Buguliskis, Ph.D. Genetic Engineering & Biotechnology News http://www.genengnews.com/insight-and-intelligence/the-big-data-addiction-ngs-has-it-bad/77900442/ www.clinicalomics.com
“As data generation approaches commoditization, the greatest challenge has shifted to effective analysis and interpretation.” -Daniel Meyer, COO at GenoSpace.

Complex complexity.Dionisio_{September 15, 2015
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Big Data: Astronomical or Genomical? Zachary D. Stephens, Skylar Y. Lee, Faraz Faghri, Roy H. Campbell, Chengxiang Zhai, Miles J. Efron, Ravishankar Iyer, Michael C. Schatz, Saurabh Sinha, Gene E. Robinson PLOS •DOI: 10.1371/journal.pbio.1002195 http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002195
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Genome researchers raise alarm over big data Storing and processing genome data will exceed the computing challenges of running YouTube and Twitter, biologists warn. Erika Check Hayden doi:10.1038/nature.2015.17912 Publication: Nature News Publisher: Nature Publishing Group http://www.nature.com/news/genome-researchers-raise-alarm-over-big-data-1.17912
Complex complexity. Work in progress... stay tuned.Dionisio_{September 15, 2015
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Big Data, Little Data, No Data https://mitpress.mit.edu/index.php?q=big-dataDionisio_{September 14, 2015
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Life Science Data Avalanche http://www.rdmag.com/articles/2015/08/combating-life-science-data-avalancheDionisio_{September 14, 2015
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The elegance of animal body plans derives from an intimate connection between function and form, which during organ formation is linked to patterning and growth. Yet, how patterning and growth are coordinated still remains largely a mystery. [...] highlight outstanding questions of how DPP coordinates patterning and growth during development.
Coordination of Patterning and Growth by the Morphogen DPP Simon Restrepo, Jeremiah J. Zartman, Konrad Basler doi:10.1016/j.cub.2014.01.055 Current Biology Volume 24, Issue 6, Pages R245–R255 http://www.sciencedirect.com/science/article/pii/S0960982214001201

Does DPP coordinate or is just an important instrument used in the coordination process? Did anybody say mystery? In the middle of the second decade of the 21st century? With the overwhelming information avalanche pouring out of research, and powerful supercomputers crunching all that data that is accumulating in the clouds, someone still dares to use the word "mystery" in relation to fundamental processes described in serious biology papers? Complex complexity. :)Dionisio_{September 14, 2015
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[...] the ability to adapt* to different temperatures by scaling the developmental rates without distinct morphological phenotypes is a common property to both vertebrate and invertebrate species. This demonstrates an impressive ability of biological developmental systems to tightly control gene activation timing and relative expression dynamics despite genetic and growth conditions differences. [...] the structure of regulatory circuits [...] buffers genetic and environmental changes [...] [...] ability of the regulatory system to overcome expression noise [...] [...] positive feedback circuitry is more efficient than other architectures in buffering noise in the inducing signal while keeping high responsivity to the level of the signal [...] [...] incoherent feedforward motifs can generate consistent response to activating input that depends mostly on fold changes in input and not on noisy absolute protein levels [...] Apparently, this flexible design of gene regulatory circuits enables them to conserve similar expression dynamics and specify similar cell types while allowing the species to keep a broad genotypic variance and survive through changing environmental conditions.
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Did anybody say "design"? (*) built-in adaptation mechanism? Complex complexity.Dionisio_{September 14, 2015
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Embryo development generates similar morphologies despite natural genetic variation and within broad environmental conditions. This flexibility of the developmental program is essential for the survival of the species and keeping a wide genotypic pool adaptable in a changing environment. Understanding the properties of the regulatory control system that underlie cell fate specification is a key to the mechanistic understanding of this developmental stability. Further studies are required to identify whether the observed shift in six1/2 expression are due to cis-regulatory modifications or due to changes in upstream input dynamics.
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Complex complexity.Dionisio_{September 14, 2015
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For these studies, we selected regulatory circuits that operate in five embryonic territories and contain common network motifs found in many other gene regulatory networks, such as positive feedback and feedforward structures. The positive feedback circuitry locks down a specification state within a cell (intracellular, *D) or within an embryonic territory (intercellular, *E) and is important for cell fate decision. Coherent and incoherent feedforward motifs (*F) are used for the sequential activation of genes in a cell. Our results portray a tight control of timing of gene activation [...] Thus our study illuminates the dynamic properties of biological regulatory systems and their ability to control relative dynamics accurately despite genetic and growth condition differences.
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Complex complexity. BTW, have we seen those basic circuits used somewhere else? :) (*) see circuits D, E and F in this picture: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435#pgen.1005435.s001Dionisio_{September 13, 2015
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The timing of gene expression depends on the temporal expression profiles of the inputs (trans) and the logic applied on the inputs by the cis-regulatory modules. [...] if two inputs are activated sequentially and the target cis-regulatory element requires both of them (necessary inputs, AND logic), the target gene will turn on only after the activation of the later input gene. If the two inputs are additive (OR logic), the target gene will turn on immediately after the activation of the earlier input gene. [...] changes in cis-regulatory logic, e.g. from AND to OR, could result in changes in gene expression timing.
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Complex complexity.Dionisio_{September 13, 2015
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Normal development requires precise temporal control of differential gene expression, yet development must be robust to natural genetic variation and environmental changes. This resilience of developmental systems is important for keeping a wide genotypic pool adaptable in changing environmental conditions [...] Identifying how the control systems overcome genetic and environmental changes is important to the mechanistic understanding of developmental processes [...]
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Complex complexity.Dionisio_{September 13, 2015
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Embryonic development necessitates a delicate balancing act. On one hand, precise regulation of the expression of developmental genes is crucial for the maintenance of morphology and function. On the other hand, these same regulatory networks must allow normal development to proceed through genetic variation and environmental changes.
Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Complex complexity.Dionisio_{September 13, 2015
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Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics Tsvia Gildor, Smadar Ben-Tabou de-Leon PLOS •DOI: 10.1371/journal.pgen.1005435 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435
Accurate temporal control of gene expression is essential for normal development and must be robust to natural genetic and environmental variation. Overall, our findings demonstrate the ability of biological developmental systems to tightly control the timing of gene activation and relative dynamics and overcome expression noise induced by genetic variation and growth conditions.

Complex complexity.Dionisio_{September 13, 2015
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Logarithmic and Power Law Input-Output Relations in Sensory Systems with Fold-Change Detection Miri Adler, Avi Mayo, Uri Alon PLOS •DOI: 10.1371/journal.pcbi.1003781 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003781
Biological sensory systems have been quantitatively studied for over 150 years. Two central biophysical laws describe sensory responses to input signals. One is a logarithmic relationship between input and output, and the other is a power law relationship. The two laws are found in a wide variety of human sensory systems including hearing, vision, taste, and weight perception; they also occur in the responses of cells to stimuli. However the mechanistic origin of these laws is not fully understood. To obtain accurate estimates, the full set of equations must be solved without setting derivatives to zero. It would be interesting to use the present approach to analyze experiments on other fold-change detection (FCD) systems, and to gain mechanistic understanding of sensory computations.

Complex complexity. Work in progress... stay tuned.Dionisio_{September 13, 2015
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Plant developmental biology in the post-genomic era Neelima Roy Sinha Front. Plant Sci., http://dx.doi.org/10.3389/fpls.2011.00011
The future looks promising as new quantitative and computer aided modeling tools, and precision dissection of gene expression, are being combined with high-throughput sequencing to answer age old questions of signaling and cell fate commitment during development of an organism.

Complex complexity. Work in progress... stay tuned.Dionisio_{September 13, 2015
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Cross-talk between TGF-beta/SMAD and integrin signaling pathways in regulating hypertrophy of mesenchymal stem cell chondrogenesis under deferral dynamic compression Tianting Zhang, Feng Wen, Yingnan Wu, Graham Seow Hng Goh, Zigang Ge, Lay Poh Tan, James Hoi Po Hui, Zheng Yan doi:10.1016/j.biomaterials.2014.10.010
The molecular mechanisms of mechanotransduction in regulating mesenchymal stem cell (MSC) chondrogenesis are not fully understood and represent an area of growing investigation.

Complex complexity.Dionisio_{September 13, 2015
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Inhibin Biosynthesis and Activity Are Limited by a Prodomain-Derived Peptide Kelly L. Walton, Emily K. Kelly, Karen L. Chan, Craig A. Harrison, and David M. Robertson DOI: http://dx.doi.org/10.1210/en.2014-2005 http://press.endocrine.org/doi/10.1210/en.2014-2005
Despite the importance of the prodomains in the regulation of inhibin biosynthesis, little is known about their contribution to inhibin bioactivity. the N-terminal region of the inhibin prodomain (pro?-peptide) is important for inhibin synthesis and bioactivity. it is hoped that this study may template the design of latency loop prodomain peptides that will serve as specific reagents for studying the in vivo functions of related TGF-? ligands.

Complex complexity.Dionisio_{September 13, 2015
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It is foreseeable that many more structural characterizations on centriole assembly will be reported in the coming years, which, together with continuous advancements in functional and in vivo studies, will provide a more refined view of one of the most important and fascinating cellular structures that has captivated cell biologists for over a century.
Building a ninefold symmetrical barrel: structural dissections of centriole assembly Gang Dong DOI: 10.1098/rsob.150082 http://rsob.royalsocietypublishing.org/content/5/8/150082

Complex complexity. Work in progress... stay tuned.Dionisio_{September 13, 2015
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