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13. Voices of biotech leaders

Author

Bill Gates, Jeantine Lunshof, Hakim Yadi, Luhan Yang, Tomas de Wouters, Sajith Wickramasekara, Xavier Duportet, Michelle Mc Murray Heath, Heather Dewey-Hagborg, Emily M LeProust, Jake Sherkow, Eddie Martucci, George M. Church, Arturo Elizondo, Teresa Tarragó, Neri Oxman, Leah V. Sibener, J. Craig Venter, Aviv Regev, Abasi Ene-Obong, Katrine Bosley, Francesco Gatto, Sebastian Giwa, Veronika Oudova, Sharon F. Terry, Silvia Gold, Spin Wang, Priscilla Chan, Jason Mellad, Christopher Thomas Scott, Charlotte Casebourn, Janice Chen, Sarah Richardson, Michael Chen, Bowen Zhao, Jeremy Farrar, Jernej Godec, and John Cumbers

Subjects
business.industry, Political science, Biomedical Engineering, MEDLINE, Molecular Medicine, Bioengineering, business, Applied Microbiology and Biotechnology, Selection (genetic algorithm), Biotechnology
Abstract

Nature Biotechnology asks a selection of leaders from across biotech to look at the future of the sector and make some predictions for the coming years.

Published
2021

18. The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding

Author

Richardson, Tomas T., Harran, Omar, and Murray, Heath

Subjects
DNA replication -- Observations, Genetic research, Nucleotides -- Properties, Genetic regulation -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

DNA replication is tightly controlled to ensure accurate inheritance of genetic information. In all organisms, initiator proteins possessing AAA+ (ATPases associated with various cellular activities) domains bind replication origins to license new rounds of DNA synthesis (1). In bacteria the master initiator protein, DnaA, is highly conserved and has two crucial DNA binding activities (2). DnaA monomers recognize the replication origin (oriC) by binding double-stranded DNA sequences (DnaA-boxes); subsequently, DnaA filaments assemble and promote duplex unwinding by engaging and stretching a single DNA strand (3-5). While the specificity for duplex DnaA-boxes by DnaA has been appreciated for over 30 years, the sequence specificity for single-strand DNA binding has remained unknown. Here we identify a new indispensable bacterial replication origin element composed of a repeating trinucleotide motif that we term the DnaA-trio. We show that the function of the DnaA-trio is to stabilize DnaA filaments on a single DNA strand, thus providing essential precision to this binding mechanism. Bioinformatic analysis detects DnaA-trios in replication origins throughout the bacterial kingdom, indicating that this element is part of the core oriC structure. The discovery and characterization of the novel DnaA-trio extends our fundamental understanding of bacterial DNA replication initiation, and because of the conserved structure of AAA+ initiator proteins these findings raise the possibility of specific recognition motifs within replication origins of higher organisms., |\ The master bacterial DNA replication initiator, DnaA, is a highly conserved multifunctional protein that utilizes distinct domains to achieve its two key DNA binding activities. DnaA recognizes double-stranded (ds)DNA [...]

Published
2016

24. Assessment of available online educational resources for patients with atrial fibrillation (Preprint)

Author

Melissa Emma Middeldorp, Ellen Lyrtzis, Kyle Murray Heath, Tanya Hall, Kadhim Kadhim, and Prashanthan Sanders

Abstract

BACKGROUND A diagnosis of atrial fibrillation (AF) often leads patients to search online for information, which can expose them to information of varied quality. OBJECTIVE We conducted a qualitative systematic review of websites for patients that contain information regarding AF. METHODS The following terms were searched on 3 search engines (Google, Yahoo and Bing): AF for patients, What is AF, AF patient information, AF educational resources. Inclusion criteria were websites with a focus on comprehensive AF information, containing information about treatment options, and written in English. We excluded websites requiring membership subscription, linked to abstracts or manuscripts, or developed by private clinics. We used the Patient Education Materials Assessment Tool (PEMAT-P/PEMAT-AV) for printable/audio-visual material to assess understandability and actionability (score range 0-100). Those with PEMAT scores of >70 meaning acceptable understandability and actionability, underwent DISCERN score to assess information content quality and reliability (score range 0-80). RESULTS The search yielded a total 720 websites which underwent full review. After excluding duplicates and those not meeting the inclusion criteria, 48 underwent full scoring. Mean overall PEMAT-P score was 68.5±17.2. Mean PEMAT-AV score was 61.1±9.4. Of the websites that scored >70% PEMAT-P, 20 (42%) underwent DISCERN scoring. Mean DISCERN score was 54.7±4.5. CONCLUSIONS There is a wide variation in the understandably, actionability and quality of websites that provide information to patients with most websites not providing patient level materials. Knowledge of quality websites could provide an important adjunct for improving individuals’ knowledge about their condition

Published
2021

38. Dynamic Control of the DNA Replication Initiation Protein DnaA by Soj/ParA

Author

Murray, Heath and Errington, Jeff

Subjects
DNA replication, DNA, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.07.044 Byline: Heath Murray (1), Jeff Errington (1) Keywords: CELLBIO; CELLCYCLE; MICROBIO Abstract: Regulation of DNA replication and segregation is essential for all cells. Orthologs of the plasmid partitioning genes parA, parB, and parS are present in bacterial genomes throughout the prokaryotic evolutionary tree and are required for accurate chromosome segregation. However, the mechanism(s) by which parABS genes ensure proper DNA segregation have remained unclear. Here we report that the ParA ortholog in B. subtilis (Soj) controls the activity of the DNA replication initiator protein DnaA. Subcellular localization of several Soj mutants indicates that Soj acts as a spatially regulated molecular switch, capable of either inhibiting or activating DnaA. We show that the classical effect of Soj inhibiting sporulation is an indirect consequence of its action on DnaA through activation of the Sda DNA replication checkpoint. These results suggest that the pleiotropy manifested by chromosomal parABS mutations could be the indirect effects of a primary activity regulating DNA replication initiation. Author Affiliation: (1) Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK Article History: Received 3 March 2008; Revised 25 May 2008; Accepted 31 July 2008 Article Note: (miscellaneous) Published: October 2, 2008

Published
2008

39. Crystal structure of NucB, a biofilm-degrading endonuclease

Author

Baslé, Arnaud, Hewitt, Lorraine, Koh, Alan, Lamb, Heather K, Thompson, Paul, Burgess, J Grant, Hall, Michael J, Hawkins, Alastair R, Murray, Heath, and Lewis, Richard J

Subjects
Models, Molecular, Deoxyribonucleases, Bacterial Proteins, Structural Biology, Protein Conformation, Biofilms, Bacillus licheniformis, DNA, Crystallography, X-Ray
Abstract

Bacterial biofilms are a complex architecture of cells that grow on moist interfaces, and are held together by a molecular glue of extracellular proteins, sugars and nucleic acids. Biofilms are particularly problematic in human healthcare as they can coat medical implants and are thus a potential source of disease. The enzymatic dispersal of biofilms is increasingly being developed as a new strategy to treat this problem. Here, we have characterized NucB, a biofilm-dispersing nuclease from a marine strain of Bacillus licheniformis, and present its crystal structure together with the biochemistry and a mutational analysis required to confirm its active site. Taken together, these data support the categorization of NucB into a unique subfamily of the ββα metal-dependent non-specific endonucleases. Understanding the structure and function of NucB will facilitate its future development into an anti-biofilm therapeutic agent.

Published
2017

42. Publisher Correction: Voices of biotech leaders

Author

Bill Gates, Charlotte Casebourn, Xavier Duportet, Sarah Richardson, Jake Sherkow, J. Craig Venter, Luhan Yang, Sajith Wickramasekara, Janice Chen, Aviv Regev, Sharon F. Terry, Tomas de Wouters, Abasi Ene-Obong, Heather Dewey-Hagborg, Jason Mellad, Eddie Martucci, Christopher Thomas Scott, Bowen Zhao, Arturo Elizondo, Francesco Gatto, Neri Oxman, Michael Chen, Veronika Oudova, Katrine Bosley, Emily M LeProust, Leah V. Sibener, Jernej Godec, Michelle Mc Murray Heath, Sebastian Giwa, John Cumbers, Hakim Yadi, Jeantine E. Lunshof, Jeremy Farrar, Silvia Gold, Spin Wang, Priscilla Chan, George M. Church, and Teresa Tarragó

Subjects
Published Erratum, Political science, Biomedical Engineering, MEDLINE, Molecular Medicine, Library science, Bioengineering, Applied Microbiology and Biotechnology, Biotechnology
Published
2021

49. Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ

Author

Gallay, Clement, primary, Sanselicio, Stefano, additional, Anderson, Mary E., additional, Soh, Young Min, additional, Liu, Xue, additional, Stamsås, Gro A., additional, Pelliciari, Simone, additional, van Raaphorst, Renske, additional, Dénéréaz, Julien, additional, Kjos, Morten, additional, Murray, Heath, additional, Gruber, Stephan, additional, Grossman, Alan D., additional, and Veening, Jan-Willem, additional

Published
2019
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