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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Comments

Arabidopsis somatic embryogenesis consists of two distinct phases: an induction phase resulting in the formation of the embryogenic tissue from the adaxial side of the cotyledons of the zygotic embryo explants and an auxin-free development phase culminating with the formation of fully developed somatic embryos.
Cellular localization of the Arabidopsis class 2 phytoglobin influences somatic embryogenesis ? Cara Godee; Mohamed M. Mira; Owen Wally; Robert D. Hill; Claudio Stasolla J Exp Bot (2017) 68 (5): 1013-1023. DOI: https://doi.org/10.1093/jxb/erx003

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The embryogenic program can be recapitulated in vitro through manipulating the media and culture components that induce cells to reprogram their developmental fate and embark along an embryogenic pathway. The genetic basis of this reprogramming is largely unknown
Cellular localization of the Arabidopsis class 2 phytoglobin influences somatic embryogenesis ? Cara Godee; Mohamed M. Mira; Owen Wally; Robert D. Hill; Claudio Stasolla J Exp Bot (2017) 68 (5): 1013-1023. DOI: https://doi.org/10.1093/jxb/erx003

Did somebody say "program"? :) Complex complexity.Dionisio_{April 9, 2017
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Embryogenesis is a crucial event in the plant life cycle. It is initiated by the formation of the zygote, which through precise and conserved cell division and differentiation patterns, generates a mature embryo consisting of an embryonic axis separating the shoot and root apical meristems and one or more cotyledons [...]
Cellular localization of the Arabidopsis class 2 phytoglobin influences somatic embryogenesis ? Cara Godee; Mohamed M. Mira; Owen Wally; Robert D. Hill; Claudio Stasolla J Exp Bot (2017) 68 (5): 1013-1023. DOI: https://doi.org/10.1093/jxb/erx003

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Glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and dermatan sulfate (DS) from various vertebrate and invertebrate sources are known to be involved in diverse cellular mechanisms during repair and regenerative processes. [...] proper sulfation of GAGs is important for A. filiformis arm regeneration [...] [...] these molecules may participate in mechanisms controlling cell proliferation.
A potential role for chondroitin sulfate/dermatan sulfate in arm regeneration in Amphiura filiformis Rashmi Ramachandra; Ramesh B Namburi; Sam T Dupont; Olga Ortega-Martinez; Toin H van Kuppevelt; Ulf Lindahl; Dorothe Spillmann? Glycobiology (2017) 27 (5): 438-449. DOI: https://doi.org/10.1093/glycob/cwx010

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It remains to be determined if either: (i) CUX1 promotes DNA looping; or (ii) CUX1 is recruited to pre-existing DNA loops. Intriguingly, SATB1, a member of the CUT homeobox superclass, regulates gene expression by fostering DNA looping and TF recruitment (61). In future work, it will be key to test if CUX1 directly facilitates DNA looping and TF recruitment in a manner similar to SATB1.
The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters ? Robert K. Arthur; Ningfei An; Saira Khan; Megan E. McNerney Nucleic Acids Res gkx218. DOI: https://doi.org/10.1093/nar/gkx218

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The CUX1 transcription factor is a conserved, essential, and ubiquitous protein recurrently mutated across cancer types. The genome-scale properties and targets of endogenous CUX1 DNA-binding have remained unknown, in any species, creating a substantial gap in our knowledge of CUX1 function.
The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters ? Robert K. Arthur; Ningfei An; Saira Khan; Megan E. McNerney Nucleic Acids Res gkx218. DOI: https://doi.org/10.1093/nar/gkx218

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DNA recombination, repair and replication are three large and vibrant research fields where each ‘R’ could deserve a series of reviews in its own right. However, as the 3Rs are tightly interwoven processes, one R can often not be fully understood without including the others. With some 10%–20% of the predicted yeast genes remaining uncharacterized, we foresee the discovery of new 3R genes in the future. We also expect to see a continued shift from traditional random genetic yeast screens toward systematic genome-wide analyses taking advantage of the genomics and cellulomics tools available in yeast setting the stage for a systems biology approach to understanding the 3R interactions. [...] the yeast model system is expected to yield pioneering insights into 3R processes for many years to come.
Editorial: 3Rs tightly intertwined to maintain genome stability ? Michael Lisby; Uffe H. Mortensen FEMS Yeast Res (2017) 17 (1): fox003. DOI: https://doi.org/10.1093/femsyr/fox003

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The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network.
Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models. Barberis M, Todd RG, van der Zee L FEMS Yeast Res. 17(1). pii: fow103. doi: 10.1093/femsyr/fow103.

Did somebody say "robustly designed"? :) Complex complexity.Dionisio_{April 9, 2017
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The data presented in this study are consistent with the notion of two, genetically separable, states of the SIN; an ‘early’ state, which is dependent upon Plo1p for its establishment, and a ‘late’ state, which is dependent upon Etd1p and Spg1p. Future studies will investigate how the transition occurs.
Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN. Wachowicz P, Chasapi A, Krapp A, Cano Del Rosario E, Schmitter D, Sage D, Unser M, Xenarios I, Rougemont J, Simanis V J Cell Sci. 128(4):741-54. doi: 10.1242/jcs.160150.

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Asymmetric events are of fundamental importance in biology. Asymmetry of centrosome behaviour and inheritance is also implicated in an increasing number of cellular and developmental processes [...] [...] a contractile actomyosin ring (CAR) is important for cytokinesis [...] and acts as a ‘guide’ for synthesis of the division septum [...] The position of the division plane is determined by signalling from the nucleus and the cell tips [...] The coordination of cytokinesis with other mitotic events is assured by a conserved network of protein kinases known as the septation initiation network (SIN).
Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN. Wachowicz P, Chasapi A, Krapp A, Cano Del Rosario E, Schmitter D, Sage D, Unser M, Xenarios I, Rougemont J, Simanis V J Cell Sci. 128(4):741-54. doi: 10.1242/jcs.160150.

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The Schizosaccharomyces pombe septation initiation network (SIN) regulates cytokinesis, and asymmetric association of SIN proteins with the mitotic spindle pole bodies (SPBs) is important for its regulation. These data reveal that multiple regulatory mechanisms control the SIN in mitosis and lead us to propose a two-state model to describe the SIN.
Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN. Wachowicz P, Chasapi A, Krapp A, Cano Del Rosario E, Schmitter D, Sage D, Unser M, Xenarios I, Rougemont J, Simanis V J Cell Sci. 128(4):741-54. doi: 10.1242/jcs.160150.

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We conclude that SIN activity is both necessary and sufficient to disperse type 1 nodes based on our previous observation that SIN-deficient cells do not disperse Cdr2p from nodes in mitosis and our present finding that hyperactivation of the SIN forces rapid dispersal of type 1 nodes in interphase and mitotic cells.
The septation initiation network controls the assembly of nodes containing Cdr2p for cytokinesis in fission yeast. Pu KM, Akamatsu M, Pollard TD J Cell Sci. 128(3):441-6. DOI: 10.1242/jcs.160077

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In the fission yeast Schizosaccharomyces pombe, cortical protein structures called interphase nodes help to prepare the cell for cytokinesis by positioning precursors of the cytokinetic contractile ring, and the septation initiation network (SIN) regulates the onset of cytokinesis and septum formation.
The septation initiation network controls the assembly of nodes containing Cdr2p for cytokinesis in fission yeast. Pu KM, Akamatsu M, Pollard TD J Cell Sci. 128(3):441-6. DOI: 10.1242/jcs.160077

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[...] the connection between the cell wall and the AR through the plasma membrane is emerging as an important condition for a successful cytokinesis and for the maintenance of cell integrity. [...] it is still unknown how this connection is accomplished [...] The characterization of new double conditional mutants, proteomics and high-resolution microscopy techniques will help to further characterize this connection.
Overview of fission yeast septation Pilar Pérez, Juan C. G. Cortés, Rebeca Martín-García, Juan C. Ribas DOI: 10.1111/cmi.12611 Cellular Microbiology Volume 18, Issue 9 Pages 1201–1207

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There are still a number of open questions on the septation process that need to be further addressed: the targets of the SIN that activate septation, the different functions of F-BAR proteins during septum formation, the role of Rho GTPases and other molecules that regulate cell wall synthesis, etc.
Overview of fission yeast septation Pilar Pérez, Juan C. G. Cortés, Rebeca Martín-García, Juan C. Ribas DOI: 10.1111/cmi.12611 Cellular Microbiology Volume 18, Issue 9 Pages 1201–1207

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Whether or how Rgf3 and Pxl1 functionally interact to transform the AR contraction into an activation signal for the biosynthetic enzymes that form the septum remains to be discovered. Whether and how the AR contractile force stimulates the cell wall machinery and how the cell wall maintains the AR and stimulates its contraction are currently major questions in fungal septation.
Overview of fission yeast septation Pilar Pérez, Juan C. G. Cortés, Rebeca Martín-García, Juan C. Ribas DOI: 10.1111/cmi.12611 Cellular Microbiology Volume 18, Issue 9 Pages 1201–1207

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Cytokinesis is the final stage of the eukaryotic cell cycle during which, after mitotic exit, the formation of a cleavage furrow separates the cell giving rise to two new cells. Cleavage furrow formation always requires the establishment and closure of a cytokinetic actomyosin ring (AR).
Overview of fission yeast septation Pilar Pérez, Juan C. G. Cortés, Rebeca Martín-García, Juan C. Ribas DOI: 10.1111/cmi.12611 Cellular Microbiology Volume 18, Issue 9 Pages 1201–1207

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Cytokinesis is the final process of the vegetative cycle, which divides a cell into two independent daughter cells once mitosis is completed. Here we review the current knowledge of the septation and separation processes in this fungus, as well as recent advances in understanding the functional interaction between the transmembrane enzymes that build the septum and the actomyosin ring proteins.
Overview of fission yeast septation Pilar Pérez, Juan C. G. Cortés, Rebeca Martín-García, Juan C. Ribas DOI: 10.1111/cmi.12611 Cellular Microbiology Volume 18, Issue 9 Pages 1201–1207

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Gradient formation of Pom1 is a key regulator of cell cycle and cell growth in fission yeast (Schizosaccharomyces pombe). A variety of models to explain Pom1 gradient formation have been proposed, a quantitative analysis and comparison of these models is, however, still missing. In this work we present four models from the literature and perform a quantitative comparison using published single-cell images of the gradient formation process. For the comparison of these partial differential equation (PDE) models we use state-of-the-art techniques for parameter estimation together with model selection. The model selection supports the hypothesis that buffering of the gradient is achieved via clustering. The selected model does, however, not ensure mass conservation, which might be considered as problematic.
Quantitative Comparison of Competing PDE Models for Pom1p Dynamics in Fission Yeast Hross, Sabrina , Fiedler, Anna , Theis, Fabian J. Hasenauer, Jan

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addendum to 2841:
[...] the cytoplasm of energy-depleted cells transitions from a fluid- to a solid-like state. [...] what is still unclear is how water is released from forming spores and re-enters into spores upon germination. Future studies will have to determine the molecular mechanisms and physical causes promoting the formation of a solid-like cytoplasm. Dissection of this important problem will require the use of sophisticated biophysical, biochemical, and genetic approaches.
A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy Matthias Christoph Munder, Daniel Midtvedt, Titus Franzmann, Elisabeth Nüske, Oliver Otto, Maik Herbig, Elke Ulbricht, Paul Müller, Anna Taubenberger, Shovamayee Maharana, Liliana Malinovska, Doris Richter, Jochen Guck, Vasily Zaburdaev, and Simon Alberti eLife. 5: e09347. doi: 10.7554/eLife.09347

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addendum to 2841:
Most organisms live in unpredictable environments, which can often lead to nutrient shortages and other conditions that limit their ability to grow. To survive in these harsh conditions, many organisms adopt a dormant state in which their metabolism slows down to conserve vital energy. When the environmental conditions improve, the organisms can return to their normal state and continue to grow.
A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy Matthias Christoph Munder, Daniel Midtvedt, Titus Franzmann, Elisabeth Nüske, Oliver Otto, Maik Herbig, Elke Ulbricht, Paul Müller, Anna Taubenberger, Shovamayee Maharana, Liliana Malinovska, Doris Richter, Jochen Guck, Vasily Zaburdaev, and Simon Alberti eLife. 5: e09347. doi: 10.7554/eLife.09347

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A long-term aim of the life sciences is to understand how organismal shape is encoded by the genome. An important challenge is to identify mechanistic links between the genes that control cell-fate decisions and the cellular machines that generate shape, therefore closing the gap between genotype and phenotype. The logic and mechanisms that integrate these different levels of shape control are beginning to be described, and recently discovered mechanisms of cross-talk and feedback are beginning to explain the remarkable robustness of organ assembly. The 'full-circle' understanding of morphogenesis that is emerging, besides solving a key puzzle in biology, provides a mechanistic framework for future approaches to tissue engineering.
From morphogen to morphogenesis and back. Gilmour D, Rembold M, Leptin M Nature. 541(7637):311-320. doi: 10.1038/nature21348.

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In humans, approximately 5 to 8 liters of air passes in and out of the lung per minute when resting. The air can vary in oxygen and CO2 concentration, may carry allergens, and confers different extents of mechanical stretch of the airway and gas-exchange surfaces. These signals are sensed, relayed, and processed into physiological outputs such as the control of pulmonary blood pressure, immune responses, and breathing rhythm, but the mechanism is unclear.
Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Branchfield K, Nantie L, Verheyden JM, Sui P, Wienhold MD, Sun X Science. 351(6274):707-10. doi: 10.1126/science.aad7969.

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The lung is constantly exposed to environmental atmospheric cues. How it senses and responds to these cues is poorly defined. Roundabout receptor (Robo) genes are expressed in pulmonary neuroendocrine cells (PNECs), a rare, innervated epithelial population.
Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Branchfield K, Nantie L, Verheyden JM, Sui P, Wienhold MD, Sun X Science. 351(6274):707-10. doi: 10.1126/science.aad7969.

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Despite the functional importance of NE cells and NEBs, their developmental course remains unclear, in part because of technical limitations in obtaining high-resolution images and quantitative analysis of the behavior of epithelial cells in the context of a 3D branching morphology. Given that NE cells are thought to be the cells of origin in highly malignant small-cell lung cancer, investigating the molecular mechanisms of NE cell migration may provide important clues toward the development of new therapeutic approaches to mitigate this malignancy [...]
Directed Migration of Pulmonary Neuroendocrine Cells toward Airway Branches Organizes the Stereotypic Location of Neuroepithelial Bodies. Noguchi M, Sumiyama K, Morimoto M Cell Rep. 13(12):2679-86. doi: 10.1016/j.celrep.2015.11.058

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The epithelium of the mammalian lung consists of various cell types that serve to support respiratory function [...] The distribution patterns of these cells are determined at the pseudoglandular stage [...] of the fetal lung, during which airway branching morphogenesis occurs and the terminal buds come to contain a population of multipotent epithelial progenitors [...] As the bronchial tree extends, descendants of the multipotent progenitor cells give rise to lineage-restricted progenitors that produce all of the differentiated cells. One such cell type, neuroendocrine (NE) cells, are bi-functional epithelial cells that are detected either as scattered solitary cells or as small clusters in the trachea to bronchioles but not the alveoli [...] These NE cell clusters are referred to as neuroepithelial bodies (NEBs), and multiple reports have shown that NEBs are frequently observed at bifurcation points of branching airways.
Directed Migration of Pulmonary Neuroendocrine Cells toward Airway Branches Organizes the Stereotypic Location of Neuroepithelial Bodies. Noguchi M, Sumiyama K, Morimoto M Cell Rep. 13(12):2679-86. doi: 10.1016/j.celrep.2015.11.058

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The airway epithelium consists of diverse cell types, including neuroendocrine (NE) cells. NE cells often localize at bifurcation points of airway tubes, forming small clusters called neuroepithelial bodies (NEBs). [...] NEBs localize at stereotypic positions in the bifurcation area irrespective of variations in size. Notch-Hes1 signaling contributes to the differentiation of solitary NE cells, regulating their number but not localization. [...] individual NE cells migrate distally to and cluster at bifurcation points, driving NEB formation. [...] NEB development is a multistep process involving differentiation of individual NE cells and their directional migration to organize NEBs.
Directed Migration of Pulmonary Neuroendocrine Cells toward Airway Branches Organizes the Stereotypic Location of Neuroepithelial Bodies. Noguchi M, Sumiyama K, Morimoto M Cell Rep. 13(12):2679-86. doi: 10.1016/j.celrep.2015.11.058

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DC hold a great promise for the therapy of human diseases. On the one hand, DC may enhance anti-tumour immunity when attempting to fight cancer. On the other hand, they may induce tolerance, which is essential in case of transplantation and autoimmunity. Nonetheless, here lies their main danger: the potential threat that the transferred cells may change once within the patients, and thus cause tolerance instead of immunity, and vice versa.
Dendritic cells as gatekeepers of tolerance Ari Waisman , Dominika Lukas, Björn E. Clausen, Nir Yogev Seminars in Immunopathology Volume 39, Issue 2, pp 153–163 DOI: 10.1007/s00281-016-0583-z

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Dendritic cells (DC) serve as unique sentinels of the immune system, continuously sampling their environment and exerting different properties that in turn determine immunological outcomes. Although DC do not serve as effector cells that fight against pathogens, they control adaptive immunity by providing essential signals that are mandatory for directing the desired immune response. Apart from antigen presentation, DC deliver co-stimulatory signals and produce cytokines, which are necessary for instructing appropriate effector or regulatory T cell responses.
Dendritic cells as gatekeepers of tolerance Ari Waisman , Dominika Lukas, Björn E. Clausen, Nir Yogev Seminars in Immunopathology Volume 39, Issue 2, pp 153–163 DOI: 10.1007/s00281-016-0583-z

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Dendritic cells (DC) are unique hematopoietic cells, linking innate and adaptive immune responses. In particular, they are considered as the most potent antigen presenting cells, governing both T cell immunity and tolerance. In view of their exceptional ability to present antigen and to interact with T cells, DC play distinct roles in shaping T cell development, differentiation and function. The outcome of the DC-T cell interaction is determined by the state of DC maturation, the type of DC subset, the cytokine microenvironment and the tissue location. Both regulatory Tcells (Tregs) and DC are indispensable for maintaining central and peripheral tolerance. Over the past decade, accumulating data indicate that DC critically contribute to Treg differentiation and homeostasis.
Dendritic cells as gatekeepers of tolerance Ari Waisman , Dominika Lukas, Björn E. Clausen, Nir Yogev Seminars in Immunopathology Volume 39, Issue 2, pp 153–163 DOI: 10.1007/s00281-016-0583-z

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