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1. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Author

Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova, Lidia M. Duncan, Alessandro M. Carabelli, Julia C. Kenyon, Andrew M. Lever, Anna De Marco, Christian Saliba, Katja Culap, Elisabetta Cameroni, Nicholas J. Matheson, Luca Piccoli, Davide Corti, Leo C. James, David L. Robertson, Dalan Bailey, Ravindra K. Gupta, Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally Corden, Ian Johnston, David Bonsall, Colin P. Smith, Ali R. Awan, Giselda Bucca, M. Estee Torok, Kordo Saeed, Jacqui A. Prieto, David K. Jackson, William L. Hamilton, Luke B. Snell, Catherine Moore, Ewan M. Harrison, Sonia Goncalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Rich Livett, Samuel Moses, Roberto Amato, Sam Nicholls, Matthew Bull, Darren L. Smith, Jeff Barrett, David M. Aanensen, Martin D. Curran, Surendra Parmar, Dinesh Aggarwal, James G. Shepherd, Matthew D. Parker, Sharon Glaysher, Matthew Bashton, Anthony P. Underwood, Nicole Pacchiarini, Katie F. Loveson, Kate E. Templeton, Cordelia F. Langford, John Sillitoe, Thushan I. de Silva, Dennis Wang, Dominic Kwiatkowski, Andrew Rambaut, Justin O’Grady, Simon Cottrell, Matthew T.G. Holden, Emma C. Thomson, Husam Osman, Monique Andersson, Anoop J. Chauhan, Mohammed O. Hassan-Ibrahim, Mara Lawniczak, Alex Alderton, Meera Chand, Chrystala Constantinidou, Meera Unnikrishnan, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Inigo Martincorena, Erik M. Volz, Andrew J. Page, Oliver G. Pybus, Andrew R. Bassett, Cristina V. Ariani, Michael H. Spencer Chapman, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yusri Taha, Martin P. McHugh, Rebecca Dewar, Aminu S. Jahun, Claire McMurray, Sarojini Pandey, James P. McKenna, Andrew Nelson, Gregory R. Young, Clare M. McCann, Scott Elliott, Hannah Lowe, Ben Temperton, Sunando Roy, Anna Price, Sara Rey, Matthew Wyles, Stefan Rooke, Sharif Shaaban, Mariateresa de Cesare, Laura Letchford, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Myra Hosmillo, Áine O’Toole, Andrew R. Hesketh, Richard Stark, Louis du Plessis, Chris Ruis, Helen Adams, Yann Bourgeois, Stephen L. Michell, Dimitris Gramatopoulos, Jonathan Edgeworth, Judith Breuer, John A. Todd, Christophe Fraser, David Buck, Michaela John, Gemma L. Kay, Steve Palmer, Sharon J. Peacock, David Heyburn, Danni Weldon, Esther Robinson, Alan McNally, Peter Muir, Ian B. Vipond, John Boyes, Venkat Sivaprakasam, Tranprit Salluja, Samir Dervisevic, Emma J. Meader, Naomi R. Park, Karen Oliver, Aaron R. Jeffries, Sascha Ott, Ana da Silva Filipe, David A. Simpson, Chris Williams, Jane A.H. Masoli, Bridget A. Knight, Christopher R. Jones, Cherian Koshy, Amy Ash, Anna Casey, Andrew Bosworth, Liz Ratcliffe, Li Xu-McCrae, Hannah M. Pymont, Stephanie Hutchings, Lisa Berry, Katie Jones, Fenella Halstead, Thomas Davis, Christopher Holmes, Miren Iturriza-Gomara, Anita O. Lucaci, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Kathryn Ann Harris, Julianne Rose Brown, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Steven Liggett, Clive Graham, Emma Swindells, Jennifer Collins, Gary Eltringham, Sharon Campbell, Patrick C. McClure, Gemma Clark, Tim J. Sloan, Carl Jones, Jessica Lynch, Ben Warne, Steven Leonard, Jillian Durham, Thomas Williams, Sam T. Haldenby, Nathaniel Storey, Nabil-Fareed Alikhan, Nadine Holmes, Christopher Moore, Matthew Carlile, Malorie Perry, Noel Craine, Ronan A. Lyons, Angela H. Beckett, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, Robert Davies, Beth Blane, Sophia T. Girgis, Mathew A. Beale, Katherine L. Bellis, Matthew J. Dorman, Eleanor Drury, Leanne Kane, Sally Kay, Samantha McGuigan, Rachel Nelson, Liam Prestwood, Shavanthi Rajatileka, Rahul Batra, Rachel J. Williams, Mark Kristiansen, Angie Green, Anita Justice, Adhyana I.K. Mahanama, Buddhini Samaraweera, Nazreen F. Hadjirin, Joshua Quick, Radoslaw Poplawski, Leanne M. Kermack, Nicola Reynolds, Grant Hall, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Robin J. Moll, Alicia Thornton, Richard Myers, Joanne Stockton, Charlotte A. Williams, Wen C. Yew, Alexander J. Trotter, Amy Trebes, George MacIntyre-Cockett, Alec Birchley, Alexander Adams, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Ember Hilvers, Hannah Jones, Hibo Asad, Jason Coombes, Johnathan M. Evans, Laia Fina, Lauren Gilbert, Lee Graham, Michelle Cronin, Sara Kumziene-Summerhayes, Sarah Taylor, Sophie Jones, Danielle C. Groves, Peijun Zhang, Marta Gallis, Stavroula F. Louka, Igor Starinskij, Chris Jackson, Marina Gourtovaia, Gerry Tonkin-Hill, Kevin Lewis, Jaime M. Tovar-Corona, Keith James, Laura Baxter, Mohammad T. Alam, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Olivia Boyd, Lily Geidelberg, Alex E. Zarebski, Jayna Raghwani, Moritz U.G. Kraemer, Joel Southgate, Benjamin B. Lindsey, Timothy M. Freeman, Jon-Paul Keatley, Joshua B. Singer, Leonardo de Oliveira Martins, Corin A. Yeats, Khalil Abudahab, Ben E.W. Taylor, Mirko Menegazzo, John Danesh, Wendy Hogsden, Sahar Eldirdiri, Anita Kenyon, Jenifer Mason, Trevor I. Robinson, Alison Holmes, James Price, John A. Hartley, Tanya Curran, Alison E. Mather, Giri Shankar, Rachel Jones, Robin Howe, Sian Morgan, Elizabeth Wastenge, Michael R. Chapman, Siddharth Mookerjee, Rachael Stanley, Wendy Smith, Timothy Peto, David Eyre, Derrick Crook, Gabrielle Vernet, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Declan T. Bradley, Tim Wyatt, Charlotte Beaver, Luke Foulser, Sophie Palmer, Carol M. Churcher, Ellena Brooks, Kim S. Smith, Katerina Galai, Georgina M. McManus, Frances Bolt, Francesc Coll, Lizzie Meadows, Stephen W. Attwood, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Garry P. Scarlett, Sarah Jeremiah, Nikki Smith, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Michelle Wantoch, Dorota Jamrozy, Stephanie Lo, Minal Patel, Verity Hill, Claire M. Bewshea, Sian Ellard, Cressida Auckland, Ian Harrison, Chloe Bishop, Vicki Chalker, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Richard Hopes, Patawee Asamaphan, Marc O. Niebel, Rory N. Gunson, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Holli Carden, Nicholas W. Machin, Kathryn A. Jackson, Shazaad S.Y. Ahmad, Ryan P. George, Lance Turtle, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Adela Alcolea-Medina, Themoula Charalampous, Amita Patel, Lisa J. Levett, Judith Heaney, Aileen Rowan, Graham P. Taylor, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adam P. Westhorpe, Riaz Jannoo, Helen L. Lowe, Angeliki Karamani, Leah Ensell, Wendy Chatterton, Monika Pusok, Ashok Dadrah, Amanda Symmonds, Graciela Sluga, Zoltan Molnar, Paul Baker, Stephen Bonner, Sarah Essex, Edward Barton, Debra Padgett, Garren Scott, Jane Greenaway, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Veena Raviprakash, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Jonathan Moore, Susanne Stonehouse, Louise Smith, Rose K. Davidson, Luke Bedford, Lindsay Coupland, Victoria Wright, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Nichola Duckworth, Sarah Walsh, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Stephen Kidd, Rebecca Williams, Laura Gifford, Kelly Bicknell, Sarah Wyllie, Allyson Lloyd, Robert Impey, Cassandra S. Malone, Benjamin J. Cogger, Nick Levene, Lynn Monaghan, Alexander J. Keeley, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Emma Betteridge, Ben W. Farr, Scott Goodwin, Michael A. Quail, Carol Scott, Lesley Shirley, Scott A.J. Thurston, Diana Rajan, Iraad F. Bronner, Louise Aigrain, Nicholas M. Redshaw, Stefanie V. Lensing, Shane McCarthy, Alex Makunin, Carlos E. Balcazar, Michael D. Gallagher, Kathleen A. Williamson, Thomas D. Stanton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine M. Sambles, David J. Studholme, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Hassan Hartman, Nikos Manesis, Vineet Patel, Juan Ledesma, Katherine A. Twohig, Elias Allara, Clare Pearson, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Paul E. Brown, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Katherine L. Smollett, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Seema Nickbakhsh, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J. Webster, Chloe L. Fisher, Adrian W. Signell, Gilberto Betancor, Harry D. Wilson, Gaia Nebbia, Flavia Flaviani, Alberto C. Cerda, Tammy V. Merrill, Rebekah E. Wilson, Marius Cotic, Nadua Bayzid, Thomas Thompson, Erwan Acheson, Steven Rushton, Sarah O’Brien, David J. Baker, Steven Rudder, Alp Aydin, Fei Sang, Johnny Debebe, Sarah Francois, Tetyana I. Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, Angela Marchbank, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Mari Morgan, Robert Beer, Safiah Afifi, Trudy Workman, William Fuller, Catherine Bresner, Adrienn Angyal, Luke R. Green, Paul J. Parsons, Rachel M. Tucker, Rebecca Brown, Max Whiteley, James Bonfield, Christoph Puethe, Andrew Whitwham, Jennifier Liddle, Will Rowe, Igor Siveroni, Thanh Le-Viet, Amy Gaskin, Rob Johnson, Irina Abnizova, Mozam Ali, Laura Allen, Ralph Anderson, Cristina Ariani, Siobhan Austin-Guest, Sendu Bala, Jeffrey Barrett, Andrew Bassett, Kristina Battleday, James Beal, Mathew Beale, Sam Bellany, Tristram Bellerby, Katie Bellis, Duncan Berger, Matt Berriman, Paul Bevan, Simon Binley, Jason Bishop, Kirsty Blackburn, Nick Boughton, Sam Bowker, Timothy Brendler-Spaeth, Iraad Bronner, Tanya Brooklyn, Sarah Kay Buddenborg, Robert Bush, Catarina Caetano, Alex Cagan, Nicola Carter, Joanna Cartwright, Tiago Carvalho Monteiro, Liz Chapman, Tracey-Jane Chillingworth, Peter Clapham, Richard Clark, Adrian Clarke, Catriona Clarke, Daryl Cole, Elizabeth Cook, Maria Coppola, Linda Cornell, Clare Cornwell, Craig Corton, Abby Crackett, Alison Cranage, Harriet Craven, Sarah Craw, Mark Crawford, Tim Cutts, Monika Dabrowska, Matt Davies, Joseph Dawson, Callum Day, Aiden Densem, Thomas Dibling, Cat Dockree, David Dodd, Sunil Dogga, Matthew Dorman, Gordon Dougan, Martin Dougherty, Alexander Dove, Lucy Drummond, Monika Dudek, Laura Durrant, Elizabeth Easthope, Sabine Eckert, Pete Ellis, Ben Farr, Michael Fenton, Marcella Ferrero, Neil Flack, Howerd Fordham, Grace Forsythe, Matt Francis, Audrey Fraser, Adam Freeman, Anastasia Galvin, Maria Garcia-Casado, Alex Gedny, Sophia Girgis, James Glover, Oliver Gould, Andy Gray, Emma Gray, Coline Griffiths, Yong Gu, Florence Guerin, Will Hamilton, Hannah Hanks, Ewan Harrison, Alexandria Harrott, Edward Harry, Julia Harvison, Paul Heath, Anastasia Hernandez-Koutoucheva, Rhiannon Hobbs, Dave Holland, Sarah Holmes, Gary Hornett, Nicholas Hough, Liz Huckle, Lena Hughes-Hallet, Adam Hunter, Stephen Inglis, Sameena Iqbal, Adam Jackson, David Jackson, Carlos Jimenez Verdejo, Matthew Jones, Kalyan Kallepally, Keely Kay, Jon Keatley, Alan Keith, Alison King, Lucy Kitchin, Matt Kleanthous, Martina Klimekova, Petra Korlevic, Ksenia Krasheninnkova, Greg Lane, Cordelia Langford, Adam Laverack, Katharine Law, Stefanie Lensing, Amanah Lewis-Wade, Jennifer Liddle, Quan Lin, Sarah Lindsay, Sally Linsdell, Rhona Long, Jamie Lovell, Jon Lovell, James Mack, Mark Maddison, Aleksei Makunin, Irfan Mamun, Jenny Mansfield, Neil Marriott, Matt Martin, Matthew Mayho, Jo McClintock, Sandra McHugh, Liz MapcMinn, Carl Meadows, Emily Mobley, Robin Moll, Maria Morra, Leanne Morrow, Kathryn Murie, Sian Nash, Claire Nathwani, Plamena Naydenova, Alexandra Neaverson, Ed Nerou, Jon Nicholson, Tabea Nimz, Guillaume G. Noell, Sarah O’Meara, Valeriu Ohan, Charles Olney, Doug Ormond, Agnes Oszlanczi, Yoke Fei Pang, Barbora Pardubska, Naomi Park, Aaron Parmar, Gaurang Patel, Maggie Payne, Sharon Peacock, Arabella Petersen, Deborah Plowman, Tom Preston, Michael Quail, Richard Rance, Suzannah Rawlings, Nicholas Redshaw, Joe Reynolds, Mark Reynolds, Simon Rice, Matt Richardson, Connor Roberts, Katrina Robinson, Melanie Robinson, David Robinson, Hazel Rogers, Eduardo Martin Rojo, Daljit Roopra, Mark Rose, Luke Rudd, Ramin Sadri, Nicholas Salmon, David Saul, Frank Schwach, Phil Seekings, Alison Simms, Matt Sinnott, Shanthi Sivadasan, Bart Siwek, Dale Sizer, Kenneth Skeldon, Jason Skelton, Joanna Slater-Tunstill, Lisa Sloper, Nathalie Smerdon, Chris Smith, Christen Smith, James Smith, Katie Smith, Michelle Smith, Sean Smith, Tina Smith, Leighton Sneade, Carmen Diaz Soria, Catarina Sousa, Emily Souster, Andrew Sparkes, Michael Spencer-Chapman, Janet Squares, Robert Stanley, Claire Steed, Tim Stickland, Ian Still, Mike Stratton, Michelle Strickland, Allen Swann, Agnieszka Swiatkowska, Neil Sycamore, Emma Swift, Edward Symons, Suzanne Szluha, Emma Taluy, Nunu Tao, Katy Taylor, Sam Taylor, Stacey Thompson, Mark Thompson, Mark Thomson, Nicholas Thomson, Scott Thurston, Dee Toombs, Benjamin Topping, Jaime Tovar-Corona, Daniel Ungureanu, James Uphill, Jana Urbanova, Philip Jansen Van, Valerie Vancollie, Paul Voak, Danielle Walker, Matthew Walker, Matt Waller, Gary Ward, Charlie Weatherhogg, Niki Webb, Alan Wells, Eloise Wells, Luke Westwood, Theo Whipp, Thomas Whiteley, Georgia Whitton, Sara Widaa, Mia Williams, Mark Wilson, and Sean Wright

Subjects
SARS-CoV-2, COVID-19, antibody escape, neutralizing antibodies, infectivity, spike mutation, Biology (General), QH301-705.5
Abstract

Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Published
2021
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2. Supplementary Table 3 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

XLSX file, 608K, Ranked gene list PNET vs. REST.

Published
2023
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3. Supplementary Figure 4 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 828K, Tumour incidence in primary and grafted tumours depend on the initial genetic mutation.

Published
2023
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4. Supplementary Table 2 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

XLSX file, 381K, PNET specific genes.

Published
2023
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5. Supplementary Table 4 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

XLSX file, 115K, Oligodendroglioma-specific genes.

Published
2023
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6. Supplementary Table 1 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

XLSX file, 433K, 2500 2-fold differentially expressed in vitro vs in vivo genes.

Published
2023
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7. Supplementary Methods and Figure Legends from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file - 112K

Published
2023
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8. Supplementary Figure 2 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 871K, Expression patterns of tumours generated in a p53/Rb background.

Published
2023
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9. Supplementary Figure 5 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 1105K, Derivation and testing of a human oligodendroglial gene signature.

Published
2023
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10. Supplementary Figure 1 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 1557K, Expression patterns of tumours generated in a p53/PTEN/Rb background.

Published
2023
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11. Supplementary Figure 7 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 736K, Derivation of a human ATRT-specific gene set.

Published
2023
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12. Supplementary Figure 6 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 929K, Derivation and testing of a human sPNET-specific gene signature.

Published
2023
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13. Supplementary Figure 3 from Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation In Vitro

Author

Sebastian Brandner, Richard G. Grundy, Denise Sheer, Kerra Pearce, Pablo Garcia Reitboeck, Thomas S. Jacques, Hazel Rogers, Angela Richard-Loendt, Matthew Ellis, Ruth Tatevossian, Tim Forshew, and Nico V. Henriquez

Abstract

PDF file, 824K, Restricted tumourigenesis in a Rb/Pten background.

Published
2023
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14. Derivation of organoids from frozen tumour material v1

Author

Hazel Rogers, Laura Letchford, Sara Vieira, Maria Garcia-Casado, Mya Fekry-Troll, Charlotte Beaver, Rachel Nelson, Hayley Francies, and Mathew Garnett

Subjects
Chemistry, Organoid, Mathematical physics
Abstract

This protocol describes the cryopreservation and subsequent derivation of organoid models from tumour tissue. It has been developed by the organoid derivation team within the Cellular Generation and Phenotyping Group at the Wellcome Sanger Institute. We have used the process to derive organoids from colon and pancreas tumours. In our experience success rates were very low for derivation from frozen oesophageal tumour tissue. The team has extensive experience in organoid derivation and have successfully banked over 100 models.

Published
2020
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15. Cryopreservation of organoid cultures v1

Author

Emily Souster, Hazel Rogers, Laura Letchford, Sara Vieira, Maria Garcia-Casado, Mya Fekry-Troll, Charlotte Beaver, Rachel Nelson, Hayley Francies, and Mathew Garnett

Subjects
Organoid, Biology, Cryopreservation, Cell biology
Abstract

This protocol defines the procedure for cryopreservation of organoid cultures. It has been developed by the organoid derivation team within the Cellular Generation and Phenotyping Group at the Wellcome Sanger Institute. The team has extensive experience passaging and expanding organoid models. The method described has mainly been used for cancer organoids derived from colon, pancreas and oesophageal tumours.

Published
2020
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16. Thawingan organoid cryovial v1

Author

Emily Souster, Hazel Rogers, Laura Letchford, Sara Vieira, Maria Garcia-Casado, Mya Fekry-Troll, Charlotte Beaver, Rachel Nelson, Hayley Francies, and Mathew Garnett

Subjects
Chemistry, Organoid, Cell biology
Abstract

This SOP defines the procedure for thawing a frozen cryovial of organoids into 1 well of a 6 well plate for further culture. It has been developed by the organoid derivation team within the Cellular Generation and Phenotyping Group at the Wellcome Sanger Institute. The team has extensive experience passaging and expanding organoid models. The method described has mainly been used for cancer organoids with successful propagation of organoids derived from colon, pancreas and oesophageal tumours.

Published
2020
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17. Derivation of organoids from primary tumour tissue v1

Author

Hazel Rogers, Laura Letchford, Sara Vieira, Maria Garcia-Casado, Mya Fekry-Troll, Charlotte Beaver, Rachel Nelson, Hayley Francies, and Mathew Garnett

Subjects
Tumour tissue, Pathology, medicine.medical_specialty, Primary (chemistry), Organoid, medicine, Derivation, Biology
Abstract

This protocol describes the derivation of organoid models from primary tumour tissue. It has been developed by the organoid derivation team within the Cellular Generation and Phenotyping Group at the Wellcome Sanger Institute. We have used the process to derive organoids from colon, pancreas and oesophageal tumours. The team has extensive experience in organoid derivation and have successfully banked over 100 models.

Published
2020
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18. Passaging cancer organoid cultures v1

Author

Hazel Rogers, Laura Letchford, Sara Vieira, Maria Garcia-Casado, Mya Fekry-Troll, Charlotte Beaver, Rachel Nelson, Hayley Francies, and Mathew Garnett

Subjects
Cancer research, Organoid, medicine, Cancer, Biology, medicine.disease
Abstract

This protocol describes the passaging of organoid cultures. It has been developed by the organoid derivation team within the Cellular Generation and Phenotyping Group at the Wellcome Sanger Institute. The team has extensive experience passaging and expanding organoid models. The method described has mainly been used for the passaging cancer organoids with successful propagation of organoids derived from colon, pancreas and oesophageal tumours.

Published
2020
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19. Feedback from winds and supernovae in massive stellar clusters – I. Hydrodynamics

Author

Julian M. Pittard and Hazel Rogers

Subjects
Physics, Solar mass, Wind power, business.industry, Molecular cloud, FOS: Physical sciences, Astronomy, Astronomy and Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, Radius, Astrophysics - Astrophysics of Galaxies, Supernova, Stars, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), Cluster (physics), Astrophysics::Solar and Stellar Astrophysics, Astrophysics::Earth and Planetary Astrophysics, business, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics, Mechanical energy
Abstract

We use 3D hydrodynamical models to investigate the effects of massive star feedback from winds and supernovae on inhomogeneous molecular material left over from the formation of a massive stellar cluster. We simulate the interaction of the mechanical energy input from a cluster with 3 O-stars into a giant molecular cloud (GMC) clump containing 3240 solar masses of molecular material within a 4 pc radius. The cluster wind blows out of the molecular clump along low-density channels, into which denser clump material is entrained. We find that the densest molecular regions are surprisingly resistant to ablation by the cluster wind, in part due to shielding by other dense regions closer to the cluster. Nonetheless, molecular material is gradually removed by the cluster wind during which mass-loading factors in excess of several 100 are obtained. Because the clump is very porous, 60-75 per cent of the injected wind energy escapes the simulation domain, with the difference being radiated. After 4.4 Myr, the massive stars in our simulation begin to explode as supernovae. The highly structured environment into which the SN energy is released allows even weaker coupling to the remaining dense material and practically all of the SN energy reaches the wider environment. The molecular material is almost completely dispersed and destroyed after 6 Myr. The escape fraction of ionizing radiation is estimated to be about 50 per cent during the first 4 Myr of the cluster's life. A similar model with a larger and more massive GMC clump reveals the same general picture, though more time is needed for it to be destroyed., Comment: 16 pages, 18 figures, accepted for publication in MNRAS

Published
2013
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21. EPND-03. RNA-SEQ GENE EXPRESSION ANALYSIS OF 106 FORMALIN-FIXED PARAFFIN-EMBEDDED PAEDIATRIC EPENDYMOMAS

Author

Timothy Ritzmann, Hazel Rogers, Andrew M Donson, Rebecca Chapman, Lisa Storer, Jennifer Ward, Alex Virasami, Thomas S Jacques, Simon ML Paine, Nicholas Foreman, and Richard G Grundy

Subjects
Ependymoma, Cancer Research, Formalin fixed paraffin embedded, business.industry, Supratentorial Neoplasm, RNA, RNA-Seq, Biology, medicine.disease, Genome, Molecular biology, Abstracts, Text mining, Oncology, Gene expression, medicine, Neurology (clinical), business
Abstract

BACKGROUND: Although ependymoma is the second most common malignant childhood brain tumour, obtaining frozen samples from extended cohorts is challenging. A large proportion of research tissue is stored in formalin-fixed, paraffin-embedded (FFPE) blocks, some many decades old. Use of these for RNA sequencing would facilitate biological studies of this enigmatic tumour. AIMS: 106 historical ependymomas were analysed to investigate the feasibility and challenges of using FFPE samples for RNA-seq and whether previously described gene expression patterns from frozen material would be replicated. METHODS: Ethics approval and consent were obtained. Pathologist confirmed ependymoma samples were collected from UK centres. 14 cases had matched frozen samples. RNA was extracted using the Qiagen FFPE Allprep kit and 1000ng per sample underwent whole transcriptome library preparation. Sequencing had a target depth of 50 million paired-end reads. Following quality control, samples were aligned using TopHat2. Differential expression analysis (DEA) was performed using EdgeR. RESULTS: Libraries were produced from all samples. The proportion of FFPE reads aligning to the genome was less than for frozen equivalents (54.2%) and showed higher inter-sample variation. Interestingly, samples with lower alignment to the genome had more reads aligning to bacterial sequences, suggesting potential contamination of the blocks. FFPE had more adapter read through when compared to the frozen samples. Clustering demonstrated 4 groups; poor quality samples, supratentorial tumours and two posterior fossa (PF) tumour groups. DEA of the PF groups showed good concordance with PFA and PFB gene expression patterns. CONCLUSIONS: RNA sequencing of historical FFPE ependymomas replicates subgroups. The benefit of investigating a wider range of samples has to be weighed against some compromise on quality. Researchers must be aware of the potential for bacterial contamination. Greater sequencing depth and more samples in addition to care over storage may help ameliorate quality issues.

Published
2017
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22. Feedback from Winds and Supernovae in Massive Stellar Clusters - II. X-Ray Emission

Author

Julian M. Pittard and Hazel Rogers

Subjects
Physics, Molecular cloud, Astrophysics::High Energy Astrophysical Phenomena, Astronomy, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Spectral line, Interstellar medium, Supernova, Stars, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Cluster (physics), Astrophysics::Solar and Stellar Astrophysics, Red supergiant, Astrophysics::Earth and Planetary Astrophysics, Blast wave, Astrophysics::Galaxy Astrophysics, Solar and Stellar Astrophysics (astro-ph.SR)
Abstract

The X-ray emission from a simulated massive stellar cluster is investigated. The emission is calculated from a 3D hydrodynamical model which incorporates the mechanical feedback from the stellar winds of 3 O-stars embedded in a giant molecular cloud clump containing 3240 M$_{\odot}$ of molecular material within a 4 pc radius. A simple prescription for the evolution of the stars is used, with the first supernova explosion at t=4.4 Myrs. We find that the presence of the GMC clump causes short-lived attenuation effects on the X-ray emission of the cluster. However, once most of the material has been ablated away by the winds the remaining dense clumps do not have a noticable effect on the attenuation compared with the assumed interstellar medium column. We determine the evolution of the cluster X-ray luminosity, L$_X$, and spectra, and generate synthetic images. The intrinsic X-ray luminosity drops from nearly 10$^{34}$ ergs s$^{-1}$ while the winds are `bottled up', to a near constant value of 1.7$\times 10^{32}\rm ergs s^{-1}$ between t=1-4 Myrs. L$_X$ reduces slightly during each star's red supergiant stage due to the depressurization of the hot gas. However, L$_X$ increases to $\approx 10^{34}\rm\,ergs s^{-1}$ during each star's Wolf-Rayet stage. The X-ray luminosity is enhanced by 2-3 orders of magnitude to $\sim 10^{37}\rm ergs s^{-1}$ for at least 4600 yrs after each supernova, at which time the blast wave leaves the grid and the X-ray luminosity drops. The X-ray luminosity of our simulation is generally considerably fainter than predicted from spherically-symmetric bubble models, due to the leakage of hot gas material through gaps in the outer shell. This process reduces the pressure within our simulation and thus the X-ray emission. However, the X-ray luminosities and temperatures which we obtain are comparable to similarly powerful massive young clusters.

Published
2014
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23. Stellar wind and supernova feedback from massive stars

Author

Hazel Rogers and Julian M. Pittard

Subjects
Physics, Astrophysics::High Energy Astrophysical Phenomena, Astronomy, Astronomy and Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, Near-Earth supernova, Stars, Supernova, Space and Planetary Science, Cluster (physics), Astrophysics::Solar and Stellar Astrophysics, Astrophysics::Earth and Planetary Astrophysics, Molecular materials, Astrophysics::Galaxy Astrophysics
Abstract

We have constructed three-dimensional hydrodynamical models to simulate the impact of massive star feedback, via winds and SNe, on inhomogeneous molecular material left over from the formation of a massive stellar cluster. We are studying the timescales for the molecular material to be removed from the environment of a massive stellar cluster and the mass and energy fluxes into the wider environment.

Published
2012
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24. Black Hole Masses and Accretion Rates in Nearby AGN

Author

Olivia Jones, Jonathan Digby-North, Mark Whittaker, Sam Rushforth, Hazel Rogers, and Stuart Lumsden

Subjects
Physics, Black hole, Supermassive black hole, Active galactic nucleus, Intermediate polar, Space and Planetary Science, Intermediate-mass black hole, Astronomy, Astronomy and Astrophysics, Quasar, Spin-flip, Accretion (astrophysics)
Abstract

We present results from a survey of the properties of the central black holes in nearby AGN. This shows that AGN radiating near Eddington are on average less massive now than at z ~ 1.

Published
2009
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