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Journal articles on the topic 'Mammalian synthetic biology'

Author: Grafiati

Published: 4 June 2021

Last updated: 6 February 2022

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1

Kis, Zoltán, Hugo Sant'Ana Pereira, Takayuki Homma, Ryan M. Pedrigi, and Rob Krams. "Mammalian synthetic biology: emerging medical applications." Journal of The Royal Society Interface 12, no. 106 (May 2015): 20141000. http://dx.doi.org/10.1098/rsif.2014.1000.

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In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

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2

Black, Joshua B., Pablo Perez-Pinera, and Charles A. Gersbach. "Mammalian Synthetic Biology: Engineering Biological Systems." Annual Review of Biomedical Engineering 19, no. 1 (June 21, 2017): 249–77. http://dx.doi.org/10.1146/annurev-bioeng-071516-044649.

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3

Mathur, Melina, Joy S. Xiang, and Christina D. Smolke. "Mammalian synthetic biology for studying the cell." Journal of Cell Biology 216, no. 1 (December 8, 2016): 73–82. http://dx.doi.org/10.1083/jcb.201611002.

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Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology.

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4

Martella, Andrea, Steven M. Pollard, Junbiao Dai, and Yizhi Cai. "Mammalian Synthetic Biology: Time for Big MACs." ACS Synthetic Biology 5, no. 10 (April 20, 2016): 1040–49. http://dx.doi.org/10.1021/acssynbio.6b00074.

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5

Aubel, Dominique, and Martin Fussenegger. "Mammalian synthetic biology - from tools to therapies." BioEssays 32, no. 4 (March 17, 2010): 332–45. http://dx.doi.org/10.1002/bies.200900149.

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6

Greber, David, and Martin Fussenegger. "Mammalian synthetic biology: Engineering of sophisticated gene networks." Journal of Biotechnology 130, no. 4 (July 2007): 329–45. http://dx.doi.org/10.1016/j.jbiotec.2007.05.014.

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7

Kim, Tackhoon, and Timothy K. Lu. "CRISPR/Cas-based devices for mammalian synthetic biology." Current Opinion in Chemical Biology 52 (October 2019): 23–30. http://dx.doi.org/10.1016/j.cbpa.2019.04.015.

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8

Katayama, Kenta, Hitoshi Mitsunobu, and Keiji Nishida. "Mammalian synthetic biology by CRISPRs engineering and applications." Current Opinion in Chemical Biology 52 (October 2019): 79–84. http://dx.doi.org/10.1016/j.cbpa.2019.05.020.

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9

Gübeli, Raphael J., Katharina Burger, and Wilfried Weber. "Synthetic biology for mammalian cell technology and materials sciences." Biotechnology Advances 31, no. 1 (January 2013): 68–78. http://dx.doi.org/10.1016/j.biotechadv.2012.01.007.

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10

Ono, Hiroki, Shunsuke Kawasaki, and Hirohide Saito. "Orthogonal Protein-Responsive mRNA Switches for Mammalian Synthetic Biology." ACS Synthetic Biology 9, no. 1 (November 25, 2019): 169–74. http://dx.doi.org/10.1021/acssynbio.9b00343.

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11

Bacchus, William, Dominique Aubel, and Martin Fussenegger. "Biomedically relevant circuit‐design strategies in mammalian synthetic biology." Molecular Systems Biology 9, no. 1 (January 2013): 691. http://dx.doi.org/10.1038/msb.2013.48.

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12

Wieland, Markus, and Martin Fussenegger. "Engineering Molecular Circuits Using Synthetic Biology in Mammalian Cells." Annual Review of Chemical and Biomolecular Engineering 3, no. 1 (July 15, 2012): 209–34. http://dx.doi.org/10.1146/annurev-chembioeng-061010-114145.

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13

Scheller, Leo, and Martin Fussenegger. "From synthetic biology to human therapy: engineered mammalian cells." Current Opinion in Biotechnology 58 (August 2019): 108–16. http://dx.doi.org/10.1016/j.copbio.2019.02.023.

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14

Haellman, Viktor, Tobias Strittmatter, Adrian Bertschi, Pascal Stücheli, and Martin Fussenegger. "A versatile plasmid architecture for mammalian synthetic biology (VAMSyB)." Metabolic Engineering 66 (July 2021): 41–50. http://dx.doi.org/10.1016/j.ymben.2021.04.003.

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15

Tigges, Marcel, and Martin Fussenegger. "Recent advances in mammalian synthetic biology—design of synthetic transgene control networks." Current Opinion in Biotechnology 20, no. 4 (August 2009): 449–60. http://dx.doi.org/10.1016/j.copbio.2009.07.009.

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16

Kopniczky, Margarita B., Caoimhe Canavan, David W. McClymont, Michael A. Crone, Lorna Suckling, Bruno Goetzmann, Velia Siciliano, James T. MacDonald, Kirsten Jensen, and Paul S. Freemont. "Cell-Free Protein Synthesis as a Prototyping Platform for Mammalian Synthetic Biology." ACS Synthetic Biology 9, no. 1 (January 3, 2020): 144–56. http://dx.doi.org/10.1021/acssynbio.9b00437.

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17

Saito, Hirohide, and Yohei Yokobayashi. "Editorial overview: Mammalian synthetic biology: from devices to multicellular systems." Current Opinion in Chemical Biology 52 (October 2019): A1—A2. http://dx.doi.org/10.1016/j.cbpa.2019.07.010.

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18

Fletcher, Liz, Susan Rosser, and Alistair Elfick. "Exploring Synthetic and Systems Biology at the University of Edinburgh." Biochemical Society Transactions 44, no. 3 (June 9, 2016): 692–95. http://dx.doi.org/10.1042/bst20160006.

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The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

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19

Ye, Haifeng, and Martin Fussenegger. "Synthetic therapeutic gene circuits in mammalian cells." FEBS Letters 588, no. 15 (May 17, 2014): 2537–44. http://dx.doi.org/10.1016/j.febslet.2014.05.003.

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20

Lu, Yanyan, Feng-Xia Liang, and Xiaozhong Wang. "A Synthetic Biology Approach Identifies the Mammalian UPR RNA Ligase RtcB." Molecular Cell 55, no. 5 (September 2014): 758–70. http://dx.doi.org/10.1016/j.molcel.2014.06.032.

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21

Lienert, Florian, Jason J. Lohmueller, Abhishek Garg, and Pamela A. Silver. "Synthetic biology in mammalian cells: next generation research tools and therapeutics." Nature Reviews Molecular Cell Biology 15, no. 2 (January 17, 2014): 95–107. http://dx.doi.org/10.1038/nrm3738.

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22

Mansouri, Maysam, Tobias Strittmatter, and Martin Fussenegger. "Light-Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology." Advanced Science 6, no. 1 (September 30, 2018): 1800952. http://dx.doi.org/10.1002/advs.201800952.

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23

Shakiba, Nika, Ross D. Jones, Ron Weiss, and Domitilla Del Vecchio. "Context-aware synthetic biology by controller design: Engineering the mammalian cell." Cell Systems 12, no. 6 (June 2021): 561–92. http://dx.doi.org/10.1016/j.cels.2021.05.011.

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24

Shimoga, Vinay, Jacob T. White, Yi Li, Eduardo Sontag, and Leonidas Bleris. "Synthetic mammalian transgene negative autoregulation." Molecular Systems Biology 9, no. 1 (January 2013): 670. http://dx.doi.org/10.1038/msb.2013.27.

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25

Bojar, Daniel, and Martin Fussenegger. "The Role of Protein Engineering in Biomedical Applications of Mammalian Synthetic Biology." Small 16, no. 27 (October 7, 2019): 1903093. http://dx.doi.org/10.1002/smll.201903093.

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26

Ho, Patrick, and Yvonne Y. Chen. "Mammalian synthetic biology in the age of genome editing and personalized medicine." Current Opinion in Chemical Biology 40 (October 2017): 57–64. http://dx.doi.org/10.1016/j.cbpa.2017.06.003.

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27

Weber, Wilfried, and Martin Fussenegger. "Engineering of Synthetic Mammalian Gene Networks." Chemistry & Biology 16, no. 3 (March 2009): 287–97. http://dx.doi.org/10.1016/j.chembiol.2009.02.005.

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28

Bonfá, Giuliano, Juan Blazquez-Roman, Rita Tarnai, and Velia Siciliano. "Precision Tools in Immuno-Oncology: Synthetic Gene Circuits for Cancer Immunotherapy." Vaccines 8, no. 4 (December 3, 2020): 732. http://dx.doi.org/10.3390/vaccines8040732.

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Engineered mammalian cells for medical purposes are becoming a clinically relevant reality thanks to advances in synthetic biology that allow enhanced reliability and safety of cell-based therapies. However, their application is still hampered by challenges including time-consuming design-and-test cycle iterations and costs. For example, in the field of cancer immunotherapy, CAR-T cells targeting CD19 have already been clinically approved to treat several types of leukemia, but their use in the context of solid tumors is still quite inefficient, with additional issues related to the adequate quality control for clinical use. These limitations can be overtaken by innovative bioengineering approaches currently in development. Here we present an overview of recent synthetic biology strategies for mammalian cell therapies, with a special focus on the genetic engineering improvements on CAR-T cells, discussing scenarios for the next generation of genetic circuits for cancer immunotherapy.

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29

Longo, Diane M., Alexander Hoffmann, Lev S. Tsimring, and Jeff Hasty. "Coherent activation of a synthetic mammalian gene network." Systems and Synthetic Biology 4, no. 1 (September 11, 2009): 15–23. http://dx.doi.org/10.1007/s11693-009-9044-5.

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30

Li, Yi, William Cockburn, John Kilpatrick, and Garry C. Whitelam. "Cytoplasmic Expression of a Soluble Synthetic Mammalian." Molecular Biotechnology 16, no. 3 (2000): 211–20. http://dx.doi.org/10.1385/mb:16:3:211.

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31

Santorelli, Marco, Daniela Perna, Akihiro Isomura, Immacolata Garzilli, Francesco Annunziata, Lorena Postiglione, Barbara Tumaini, Ryoichiro Kageyama, and Diego di Bernardo. "Reconstitution of an Ultradian Oscillator in Mammalian Cells by a Synthetic Biology Approach." ACS Synthetic Biology 7, no. 5 (May 4, 2018): 1447–55. http://dx.doi.org/10.1021/acssynbio.8b00083.

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32

Kojima, Ryosuke, and Martin Fussenegger. "Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will." ChemBioChem 20, no. 8 (March 21, 2019): 994–1002. http://dx.doi.org/10.1002/cbic.201800682.

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33

Angelici, Bartolomeo, Erik Mailand, Benjamin Haefliger, and Yaakov Benenson. "Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells." Cell Reports 16, no. 9 (August 2016): 2525–37. http://dx.doi.org/10.1016/j.celrep.2016.07.061.

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34

Tomoda, Kiichiro, and Cody Kime. "Synthetic embryology: Early mammalian embryo modeling systems from cell cultures." Development, Growth & Differentiation 63, no. 2 (February 2021): 116–26. http://dx.doi.org/10.1111/dgd.12713.

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35

Metzger, Jakob J., Mijo Simunovic, and Ali H. Brivanlou. "Synthetic embryology: controlling geometry to model early mammalian development." Current Opinion in Genetics & Development 52 (October 2018): 86–91. http://dx.doi.org/10.1016/j.gde.2018.06.006.

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36

Balmus, Gabriel, Ana C. Barros, Paul W. G. Wijnhoven, Chloé Lescale, Hélène Lenden Hasse, Katharina Boroviak, Carlos le Sage, et al. "Synthetic lethality between PAXX and XLF in mammalian development." Genes & Development 30, no. 19 (October 1, 2016): 2152–57. http://dx.doi.org/10.1101/gad.290510.116.

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37

Weber, Wilfried, Marco Schuetz, Nicolas Dénervaud, and Martin Fussenegger. "A synthetic metabolite-based mammalian inter-cell signaling system." Molecular BioSystems 5, no. 7 (2009): 757. http://dx.doi.org/10.1039/b902070p.

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38

Wightman, Raymond, and C. J. Luo. "From mammalian tissue engineering to 3D plant cell culture." Biochemist 38, no. 4 (August 1, 2016): 32–35. http://dx.doi.org/10.1042/bio03804032.

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Recent advances applying mammalian tissue engineering to in vitro plant cell culture have successfully cultured single plant cells in a 3D microstructure, leading to the discovery of plant cell behaviours that were previously not envisaged. Animal and plant cells share a number of properties that rely on a hierarchical microenvironment for creating complex tissues. Both mammalian tissue engineering and 3D plant culture employ tailored scaffolds that alter a cell's behaviour from the initial culture used for seeding. For humans, these techniques are revolutionizing healthcare strategies, particularly in regenerative medicine and cancer studies. For plants, we predict applications both in fundamental research to study morphogenesis and for synthetic biology in the agri-biotech sector.

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39

Yang, Ye, Michael A. Lampson, and Ben E. Black. "Centromere identity and function put to use: construction and transfer of mammalian artificial chromosomes to animal models." Essays in Biochemistry 64, no. 2 (June 5, 2020): 185–92. http://dx.doi.org/10.1042/ebc20190071.

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Abstract Mammalian artificial chromosomes (MACs) are widely used as gene expression vectors and have various advantages over conventional expression vectors. We review and discuss breakthroughs in MAC construction, initiation of functional centromeres allowing their faithful inheritance, and transfer from cell culture to animal model systems. These advances have contributed to advancements in synthetic biology, biomedical research, and applications in industry and in the clinic.

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40

Lanza, Amanda M., Joseph K. Cheng, and Hal S. Alper. "Emerging synthetic biology tools for engineering mammalian cell systems and expediting cell line development." Current Opinion in Chemical Engineering 1, no. 4 (November 2012): 403–10. http://dx.doi.org/10.1016/j.coche.2012.09.005.

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41

Li, Chuanyin, Tianting Han, Rong Guo, Peng Chen, Chao Peng, Gali Prag, and Ronggui Hu. "An Integrative Synthetic Biology Approach to Interrogating Cellular Ubiquitin and Ufm Signaling." International Journal of Molecular Sciences 21, no. 12 (June 14, 2020): 4231. http://dx.doi.org/10.3390/ijms21124231.

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Global identification of substrates for PTMs (post-translational modifications) represents a critical but yet dauntingly challenging task in understanding biology and disease pathology. Here we presented a synthetic biology approach, namely ‘YESS’, which coupled Y2H (yeast two hybrid) interactome screening with PTMs reactions reconstituted in bacteria for substrates identification and validation, followed by the functional validation in mammalian cells. Specifically, the sequence-independent Gateway® cloning technique was adopted to afford simultaneous transfer of multiple hit ORFs (open reading frames) between the YESS sub-systems. In proof-of-evidence applications of YESS, novel substrates were identified for UBE3A and UFL1, the E3 ligases for ubiquitination and ufmylation, respectively. Therefore, the YESS approach could serve as a potentially powerful tool to study cellular signaling mediated by different PTMs.

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42

Nickoloff, J. A., and R. J. Reynolds. "Transcription stimulates homologous recombination in mammalian cells." Molecular and Cellular Biology 10, no. 9 (September 1990): 4837–45. http://dx.doi.org/10.1128/mcb.10.9.4837-4845.1990.

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Transcription stimulates homologous recombination in Saccharomyces cerevisiae and has been implicated in the control of recombinational events during the development of mammalian immune systems. Here, we describe a plasmid-based system in which an inducible promoter from the mouse mammary tumor virus is located upstream of heteroallelic neomycin genes carried on two plasmids. Pairs of plasmids are introduced into Chinese hamster ovary cells by electroporation, and recombination is monitored by scoring colonies resistant to the aminoglycoside G418. When transcription is induced with dexamethasone, a synthetic glucocorticoid hormone, and double-strand breaks are introduced at mutation sites, recombination is stimulated sixfold over noninduced levels. Inducing transcription in circular substrates or in substrates cleaved at sites distant from the mutations has no detectable effect on recombination between neomycin genes. Results are presented that are consistent with the observed stimulation of recombination occurring before plasmids integrate into the cellular DNA. Our results are discussed in relation to molecular models for extrachromosomal recombination in mammalian cells.

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43

Ritter, D., J. Chao, P. Needleman, E. Tetens, and J. E. Greenwald. "Localization, synthetic regulation, and biology of renal atriopeptin-like prohormone." American Journal of Physiology-Renal Physiology 263, no. 3 (September 1, 1992): F503—F509. http://dx.doi.org/10.1152/ajprenal.1992.263.3.f503.

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We recently demonstrated the synthesis and secretion of an atriopeptin (AP)-like prohormone in rat neonatal and adult cortical kidney cell cultures. However, these cultures contained proximal as well as distal tubular epithelial cells; thus characterization of the peptide synthetic cell was not possible. Also, by immunohistochemical techniques, we localized this AP-like prohormone to the distal cortical nephron in adult rat kidney. In this study, we examined further details of the kidney cortical cell type that expresses and secretes this AP-like peptide in adult renal cortical cell cultures, its regulation by adenylate cyclase via adenosine 3',5'-cyclic monophosphate (cAMP) generation, and its ability to stimulate guanylate cyclase. Tubular fragments were derived from cortical tissue of adult Sprague-Dawley rats and separated into four fractions on Percoll density gradient. Cell cultures generated from fraction 3 secreted 5- to 10-fold the amount of this renal peptide compared with fractions 2 and 4. Further cell culture characterization was performed by agonist-stimulated cAMP formation, kallikrein localization, and prostaglandin E2 formation. From these analyses, it was determined that tissue band 3 was enriched for distal cortical connecting tubules. To further evaluate whether mammalian distal nephron synthesizes an AP-like protein, we determined that two immortalized mouse cell lines, derived from either the distal convoluted tubule or cortical collecting tubule, synthesized a radiolabeled AP after being pulsed with [35S]-methionine.(ABSTRACT TRUNCATED AT 250 WORDS)

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44

Patel, V. P., and H. F. Lodish. "The fibronectin receptor on mammalian erythroid precursor cells: characterization and developmental regulation." Journal of Cell Biology 102, no. 2 (February 1, 1986): 449–56. http://dx.doi.org/10.1083/jcb.102.2.449.

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The plasma membrane of murine erythro-leukemia (MEL) cells contains a 140-kD protein that binds specifically to fibronectin. A 125I-labeled 140-kD protein from surface-labeled uninduced MEL cells was specifically bound by an affinity matrix that contained the 115-kD cell binding fragment of fibronectin, and specifically eluted by a synthetic peptide that has cell attachment-promoting activity. The loss of this protein during erythroid differentiation was correlated with loss of cellular adhesion to fibronectin. Both MEL cells and reticulocytes attached to the same site on fibronectin as do fibroblasts since adhesion of erythroid cells to fibronectin was specifically blocked by a monoclonal antibody directed against the cell-binding fragment of fibronectin and by a synthetic peptide containing the Arg-Gly-Asp-Ser sequence found in the cell-binding fragment of fibronectin. Erythroid cells attached specifically to surfaces coated either with the 115-kD cell-binding fragment of fibronectin or with the synthetic peptide-albumin complex. Thus, the erythroid 140-kD protein exhibits several properties in common with those described for the fibronectin receptor of fibroblasts. We propose that loss or modification of this protein at the cell surface is responsible for the loss of cellular adhesion to fibronectin during erythroid differentiation.

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45

Zeisig, Bernd B., and Chi Wai Eric So. "Therapeutic Opportunities of Targeting Canonical and Noncanonical PcG/TrxG Functions in Acute Myeloid Leukemia." Annual Review of Genomics and Human Genetics 22, no. 1 (August 31, 2021): 103–25. http://dx.doi.org/10.1146/annurev-genom-111120-102443.

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Transcriptional deregulation is a key driver of acute myeloid leukemia (AML), a heterogeneous blood cancer with poor survival rates. Polycomb group (PcG) and Trithorax group (TrxG) genes, originally identified in Drosophila melanogaster several decades ago as master regulators of cellular identity and epigenetic memory, not only are important in mammalian development but also play a key role in AML disease biology. In addition to their classical canonical antagonistic transcriptional functions, noncanonical synergistic and nontranscriptional functions of PcG and TrxG are emerging. Here, we review the biochemical properties of major mammalian PcG and TrxG complexes and their roles in AML disease biology, including disease maintenance as well as drug resistance. We summarize current efforts on targeting PcG and TrxG for treatment of AML and propose rational synthetic lethality and drug-induced antagonistic pleiotropy options involving PcG and TrxG as potential new therapeutic avenues for treatment of AML.

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46

Tycko, Josh, Mike V. Van, Michael B. Elowitz, and Lacramioara Bintu. "Advancing towards a global mammalian gene regulation model through single-cell analysis and synthetic biology." Current Opinion in Biomedical Engineering 4 (December 2017): 174–93. http://dx.doi.org/10.1016/j.cobme.2017.10.011.

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47

Didion, B. A., and R. Bleher. "261 LABELING SEX-SPECIFIC DNA SEQUENCES IN MAMMALIAN SPERM." Reproduction, Fertility and Development 20, no. 1 (2008): 210. http://dx.doi.org/10.1071/rdv20n1ab261.

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While flow cytometric separation of X- andY-chromosome- bearing sperm has advanced to the point of acceptance in the commercial production of sex-preselected cattle, it is important to continue researching this area to improve efficiencies. For example, the difference in DNA sequence between the X- andY-chromosomes has merit as a foundation for an alternative sperm sexing approach that could enable the complete separation and use of an entire ejaculate. We used synthetic DNA mimics conjugated to a fluorescent dye for in situ detection of Y-chromosomes in metaphase preparations of porcine somatic cells and spermatozoa. Peptide nucleic acids (PNA) are synthetic compounds with higher affinity and stability than conventional DNA probes and are used as specific hybridization probes to complementary DNA. The application of PNA probes was demonstrated previously in telomere analysis studies, and we confirmed their efficacy using a CY3-(CCCTAA)3 PNA to probe bull and boar sperm telomeric sequences. Using male porcine somatic cells and theY-chromosome as a template, we arranged for the synthesis of a CY3-conjugated PNA to bind 13-15 base pairs of unique, Y-chromosome sequence. By testing different labeling conditions, we found that brief incubation of metaphase chromosomes with the PNA produced a localized signal on theY-chromosome. No signals were present when chromosomes of porcine female somatic cells were incubated with the PNA probes. Because chromosomes occupy non-random territories in all cell nuclei including those in sperm, we expected to find centrally located signals in 50% of fixed boar sperm when these were treated with the same PNA as used for the somatic cells. We found the signals present in 161 of 302 (53.3%) sperm to consist of a single, centrally located, round fluorescent dot in the sperm head. Further research is required to establish the uptake of PNA in live sperm toward evaluation of this approach for sperm sexing.

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48

Nuell, M. J., D. A. Stewart, L. Walker, V. Friedman, C. M. Wood, G. A. Owens, J. R. Smith, E. L. Schneider, R. Dell' Orco, and C. K. Lumpkin. "Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells." Molecular and Cellular Biology 11, no. 3 (March 1991): 1372–81. http://dx.doi.org/10.1128/mcb.11.3.1372-1381.1991.

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Genes that act inside the cell to negatively regulate proliferation are of great interest because of their implications for such processes as development and cancer, but these genes have been difficult to clone. This report details the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts and HeLa cells. Microinjection of an antisense oligonucleotide stimulates entry into S phase. By sequence comparison, the prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that is vital for normal development.

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49

Randall, K., M. Lever, B. A. Peddie, and S. T. Chambers. "Accumulation of natural and synthetic betaines by a mammalian renal cell line." Biochemistry and Cell Biology 74, no. 2 (March 1, 1996): 283–87. http://dx.doi.org/10.1139/o96-030.

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Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2–5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of omer betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because α-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.Key words: MDCK cells, betaine accumulation, osmolytes, betaine analogues.

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Li, Qiuye, Fei Wang, Xiangzhu Xiao, Chae Kim, Jen Bohon, Janna Kiselar, Jiri G. Safar, Jiyan Ma, and Witold K. Surewicz. "Structural attributes of mammalian prion infectivity: Insights from studies with synthetic prions." Journal of Biological Chemistry 293, no. 48 (October 1, 2018): 18494–503. http://dx.doi.org/10.1074/jbc.ra118.005622.

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