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1. The regulation of CDK activity by cyclins

Author

Basu, Souradeep, Nurse, Paul, and Freemont, Paul

Abstract

In eukaryotes, the two major cell cycle events of DNA replication and chromosome segregation are directed by Cyclin Dependent Kinases (CDKs) in combination with G1/S cyclins (S-CDK) and G2/M cyclins (M-CDK), respectively. It is still unclear what differentiates S-CDK activity from M-CDK activity, and how much functional redundancy exists between cyclin-CDK complexes. Here the fission yeast G1/S cyclin-CDK complex, Cig2-Cdc2, is used to study S-CDK. It is shown that S-CDK is capable of achieving high levels of CDK activity, but is incapable of executing mitosis. However, deletion of Protein Phosphatase 1 (PP1) allows for mitotic progression, and is therefore responsible for restricting S-CDK from executing mitosis. Substrates at the yeast centrosome equivalent, the spindle pole body (SPB), are phosphorylated poorly by S-CDK. Consistent with this idea, removal of PP1 at the SPB alone allows S-CDK to drive mitosis. Phosphoproteomic analysis then shows that S-CDK and M-CDK have subtly different in vivo CDK substrate preferences, but that the majority of substrates experience S-CDK and M-CDK activity equally. Using a CDK mutant that does not need cyclin binding for activity, evidence is presented suggesting that generic CDK activity without cyclins is sufficient for S-phase, but that cyclin-associated CDK activity is required for mitosis. In pursuit of why cyclins are essential for mitosis, the substrate docking region of the mitotic cyclin Cdc13 is mutated. The mutation of this region does not affect Cdc13-dependent S-phase progression, but cells fail to execute mitosis. Mutant Cdc13 is unable to localise correctly to the interphase SPB, and phosphoproteomic analysis suggests that this defect causes reduced CDK substrate phosphorylation at the SPB, preventing mitosis. These data are consistent with the idea that cyclins regulate CDK localisation at mitosis to influence CDK substrate selection, and suggests that correctly regulated CDK activity across cellular compartments is needed to execute mitosis.

Published
2021
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3. Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

Author

Aitken, Jim, Allen, Zoe, Ambler, Rachel, Ambrose, Karen, Ashton, Emma, Avola, Alida, Balakrishnan, Samutheswari, Barns-Jenkins, Caitlin, Barr, Genevieve, Barrell, Sam, Basu, Souradeep, Beale, Rupert, Beesley, Clare, Bhardwaj, Nisha, Bibi, Shahnaz, Bineva-Todd, Ganka, Biswas, Dhruva, Blackman, Michael J., Bonnet, Dominique, Bowker, Faye, Broncel, Malgorzata, Brooks, Claire, Buck, Michael D., Buckton, Andrew, Budd, Timothy, Burrell, Alana, Busby, Louise, Bussi, Claudio, Butterworth, Simon, Byott, Matthew, Byrne, Fiona, Byrne, Richard, Caidan, Simon, Campbell, Joanna, Canton, Johnathan, Cardoso, Ana, Carter, Nick, Carvalho, Luiz, Carzaniga, Raffaella, Chandler, Natalie, Chen, Qu, Cherepanov, Peter, Churchward, Laura, Clark, Graham, Clayton, Bobbi, Cobolli Gigli, Clementina, Collins, Zena, Cottrell, Sally, Crawford, Margaret, Cubitt, Laura, Cullup, Tom, Davies, Heledd, Davis, Patrick, Davison, Dara, Dearing, Vicky, Debaisieux, Solene, Diaz-Romero, Monica, Dibbs, Alison, Diring, Jessica, Driscoll, Paul C., D'Avola, Annalisa, Earl, Christopher, Edwards, Amelia, Ekin, Chris, Evangelopoulos, Dimitrios, Faraway, Rupert, Fearns, Antony, Ferron, Aaron, Fidanis, Efthymios, Fitz, Dan, Fleming, James, Frampton, Daniel, Frederico, Bruno, Gaiba, Alessandra, Gait, Anthony, Gamblin, Steve, Gärtner, Kathleen, Gaul, Liam, Golding, Helen M., Goldman, Jacki, Goldstone, Robert, Gomez Dominguez, Belen, Gong, Hui, Grant, Paul R., Greco, Maria, Grobler, Mariana, Guedan, Anabel, Gutierrez, Maximiliano G., Hackett, Fiona, Hall, Ross, Halldorsson, Steinar, Harris, Suzanne, Hashim, Sugera, Hatipoglu, Emine, Healy, Lyn, Heaney, Judith, Herbst, Susanne, Hewitt, Graeme, Higgins, Theresa, Hindmarsh, Steve, Hirani, Rajnika, Hope, Joshua, Horton, Elizabeth, Hoskins, Beth, Howell, Michael, Howitt, Louise, Hoyle, Jacqueline, Htun, Mint R., Hubank, Michael, Huerga Encabo, Hector, Hughes, Deborah, Hughes, Jane, Huseynova, Almaz, Hwang, Ming-Shih, Instrell, Rachael, Jackson, Deborah, Jamal-Hanjani, Mariam, Jenkins, Lucy, Jiang, Ming, Johnson, Mark, Jones, Leigh, Kanu, Nnennaya, Kassiotis, George, Kelly, Gavin, Kiely, Louise, Teixeira, Anastacio King Spert, Kirk, Stuart, Kjaer, Svend, Knuepfer, Ellen, Komarov, Nikita, Kotzampaltiris, Paul, Kousis, Konstantinos, Krylova, Tammy, Kucharska, Ania, Labrum, Robyn, Lambe, Catherine, Lappin, Michelle, Lee, Stacey-Ann, Levett, Andrew, Levett, Lisa, Levi, Marcel, Liu, Hon Wing, Loughlin, Sam, Lu, Wei-Ting, MacRae, James I., Madoo, Akshay, Marczak, Julie A., Martensson, Mimmi, Martinez, Thomas, Marzook, Bishara, Matthews, John, Matz, Joachim M., McCall, Samuel, McCoy, Laura E., McKay, Fiona, McNamara, Edel C., Minutti, Carlos M., Mistry, Gita, Molina-Arcas, Miriam, Montaner, Beatriz, Montgomery, Kylie, Moore, Catherine, Moore, David, Moraiti, Anastasia, Moreira-Teixeira, Lucia, Mukherjee, Joyita, Naceur-Lombardelli, Cristina, Nelson, Aileen, Nicod, Jerome, Nightingale, Luke, Nofal, Stephanie, Nurse, Paul, Nutan, Savita, Oedekoven, Caroline, O'Garra, Anne, O'Leary, Jean D., Olsen, Jessica, O'Neill, Olga, O'Reilly, Nicola, Suarez, Paula Ordonez, Osborne, Neil, Pabari, Amar, Pajak, Aleksandra, Papayannopoulos, Venizelos, Paraskevopoulou, Stavroula M, Patel, Namita, Patel, Yogen, Paun, Oana, Peat, Nigel, Peces-Barba Castano, Laura, Caballero, Ana Perez, Perez-Lloret, Jimena, Perrault, Magali S., Perrin, Abigail, Poh, Roy, Poirier, Enzo Z., Polke, James M., Pollitt, Marc, Prieto-Godino, Lucia, Proust, Alize, Puvirajasinghe, Clinda, Queval, Christophe, Ramachandran, Vijaya, Ramaprasad, Abhinay, Ratcliffe, Peter, Reed, Laura, Reis e Sousa, Caetano, Richardson, Kayleigh, Ridewood, Sophie, Roberts, Fiona, Roberts, Rowenna, Rodgers, Angela, Romero Clavijo, Pablo, Rosa, Annachiara, Rossi, Alice, Roustan, Chloe, Rowan, Andrew, Sahai, Erik, Sait, Aaron, Sala, Katarzyna, Sanchez, Emilie, Sanderson, Theo, Santucci, Pierre, Sardar, Fatima, Sateriale, Adam, Saunders, Jill A., Sawyer, Chelsea, Schlott, Anja, Schweighoffer, Edina, Segura-Bayona, Sandra, Shah Punatar, Rajvee, Shahmanesh, Maryam, Shaw, Joe, Silva Dos Santos, Mariana, Silvestre, Margaux, Singer, Matthew, Snell, Daniel M., Song, Ok-Ryul, Spyer, Moira J., Steel, Louisa, Strange, Amy, Sullivan, Adrienne E., Tan, Michele S.Y., Tautz-Davis, Zoe H., Taylor, Effie, Taylor, Gunes, Taylor, Harriet B., Taylor-Beadling, Alison, Teixeira Subtil, Fernanda, Terré Torras, Berta, Toolan-Kerr, Patrick, Torelli, Francesca, Toteva, Tea, Treeck, Moritz, Trojer, Hadija, Tsai, Ming-Han C., Turner, James M.A., Turner, Melanie, Ule, Jernej, Ulferts, Rachel, Vanloo, Sharon P., Veeriah, Selvaraju, Venkatesan, Subramanian, Vousden, Karen, Wack, Andreas, Walder, Claire, Walker, Philip A., Wang, Yiran, Ward, Sophia, Wenman, Catharina, Williams, Luke, Williams, Matthew J., Keong Wong, Wai, Wright, Joshua, Wu, Mary, Wynne, Lauren, Xiang, Zheng, Yap, Melvyn, Zagalak, Julian A., Zecchin, Davide, Zillwood, Rachel, Carthiyaniamma, Santhakumari, DeTisi, Jane, Dick, Julie, Hill, Andrea, Kipper, Karin, Kullar, Birinder, Norris, Sarah, Rugg-Gunn, Fergus, Salvatierra, Rebecca, Shaya, Gabriel, Sloan, Astrid, Singh, Priyanka, Varley, James, Whatley, Ben, Balestrini, Simona, Koepp, Matthias J., Gandhi, Sonia, Rickman, Hannah M., Shin, Gee Yen, Houlihan, Catherine F., Anders-Cannon, Jonny, Silvennoinen, Katri, Xiao, Fenglai, Zagaglia, Sara, Hudgell, Kirsty, Ziomek, Mariusz, Haimes, Paul, Sampson, Adam, Parker, Annie, Helen Cross, J., Pardington, Rosemarie, Nastouli, Eleni, Swanton, Charles, Sander, Josemir W., and Sisodiya, Sanjay M.

Published
2021
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4. Structural Insights into the Broad-Spectrum Antiviral Target Endoplasmic Reticulum Alpha-Glucosidase II

Author

Caputo, Alessandro T., Alonzi, Dominic S., Kiappes, John L., Struwe, Weston B., Cross, Alice, Basu, Souradeep, Darlot, Benoit, Roversi, Pietro, Zitzmann, Nicole, COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, REZAEI, NIMA, Series Editor, Hilgenfeld, Rolf, editor, and Vasudevan, Subhash G., editor

Published
2018
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7. Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint

Author

Roversi, Pietro, Marti, Lucia, Caputo, Alessandro T., Alonzi, Dominic S., Hill, Johan C., Dent, Kyle C., Kumar, Abhinav, Levasseur, Mikail D., Lia, Andrea, Waksman, Thomas, Basu, Souradeep, Albrecht, Yentli Soto, Qian, Kristin, McIvor, James Patrick, Lipp, Colette B., Siliqi, Dritan, Vasiljević, Snežana, Mohammed, Shabaz, Lukacik, Petra, Walsh, Martin A., Santino, Angelo, and Zitzmann, Nicole

Published
2017

12. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease

Author

Canal, Berta, primary, McClure, Allison W., additional, Curran, Joseph F., additional, Wu, Mary, additional, Ulferts, Rachel, additional, Weissmann, Florian, additional, Zeng, Jingkun, additional, Bertolin, Agustina P., additional, Milligan, Jennifer C., additional, Basu, Souradeep, additional, Drury, Lucy S., additional, Deegan, Tom D., additional, Fujisawa, Ryo, additional, Roberts, Emma L., additional, Basier, Clovis, additional, Labib, Karim, additional, Beale, Rupert, additional, Howell, Michael, additional, and Diffley, John F.X., additional

Published
2021
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13. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase

Author

Basu, Souradeep, primary, Mak, Tiffany, additional, Ulferts, Rachel, additional, Wu, Mary, additional, Deegan, Tom, additional, Fujisawa, Ryo, additional, Tan, Kang Wei, additional, Lim, Chew Theng, additional, Basier, Clovis, additional, Canal, Berta, additional, Curran, Joseph F., additional, Drury, Lucy S., additional, McClure, Allison W., additional, Roberts, Emma L., additional, Weissmann, Florian, additional, Zeisner, Theresa U., additional, Beale, Rupert, additional, Cowling, Victoria H., additional, Howell, Michael, additional, Labib, Karim, additional, and Diffley, John F.X., additional

Published
2021
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16. Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase

Author

Basu, Souradeep, primary, Mak, Tiffany, additional, Ulferts, Rachel, additional, Wu, Mary, additional, Deegan, Tom, additional, Fujisawa, Ryo, additional, Tan, Kang Wei, additional, Lim, Chew Theng, additional, Basier, Clovis, additional, Canal, Berta, additional, Curran, Joseph F., additional, Drury, Lucy, additional, McClure, Allison W., additional, Roberts, Emma L., additional, Weissmann, Florian, additional, Zeisner, Theresa U., additional, Beale, Rupert, additional, Cowling, Victoria H., additional, Howell, Michael, additional, Labib, Karim, additional, and Diffley, John F.X., additional

Published
2021
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17. Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

Author

Balestrini, Simona, primary, Koepp, Matthias J., additional, Gandhi, Sonia, additional, Rickman, Hannah M., additional, Shin, Gee Yen, additional, Houlihan, Catherine F., additional, Anders-Cannon, Jonny, additional, Silvennoinen, Katri, additional, Xiao, Fenglai, additional, Zagaglia, Sara, additional, Hudgell, Kirsty, additional, Ziomek, Mariusz, additional, Haimes, Paul, additional, Sampson, Adam, additional, Parker, Annie, additional, Helen Cross, J., additional, Pardington, Rosemarie, additional, Nastouli, Eleni, additional, Swanton, Charles, additional, Sander, Josemir W., additional, Sisodiya, Sanjay M., additional, Aitken, Jim, additional, Allen, Zoe, additional, Ambler, Rachel, additional, Ambrose, Karen, additional, Ashton, Emma, additional, Avola, Alida, additional, Balakrishnan, Samutheswari, additional, Barns-Jenkins, Caitlin, additional, Barr, Genevieve, additional, Barrell, Sam, additional, Basu, Souradeep, additional, Beale, Rupert, additional, Beesley, Clare, additional, Bhardwaj, Nisha, additional, Bibi, Shahnaz, additional, Bineva-Todd, Ganka, additional, Biswas, Dhruva, additional, Blackman, Michael J., additional, Bonnet, Dominique, additional, Bowker, Faye, additional, Broncel, Malgorzata, additional, Brooks, Claire, additional, Buck, Michael D., additional, Buckton, Andrew, additional, Budd, Timothy, additional, Burrell, Alana, additional, Busby, Louise, additional, Bussi, Claudio, additional, Butterworth, Simon, additional, Byott, Matthew, additional, Byrne, Fiona, additional, Byrne, Richard, additional, Caidan, Simon, additional, Campbell, Joanna, additional, Canton, Johnathan, additional, Cardoso, Ana, additional, Carter, Nick, additional, Carvalho, Luiz, additional, Carzaniga, Raffaella, additional, Chandler, Natalie, additional, Chen, Qu, additional, Cherepanov, Peter, additional, Churchward, Laura, additional, Clark, Graham, additional, Clayton, Bobbi, additional, Cobolli Gigli, Clementina, additional, Collins, Zena, additional, Cottrell, Sally, additional, Crawford, Margaret, additional, Cubitt, Laura, additional, Cullup, Tom, additional, Davies, Heledd, additional, Davis, Patrick, additional, Davison, Dara, additional, Dearing, Vicky, additional, Debaisieux, Solene, additional, Diaz-Romero, Monica, additional, Dibbs, Alison, additional, Diring, Jessica, additional, Driscoll, Paul C., additional, D'Avola, Annalisa, additional, Earl, Christopher, additional, Edwards, Amelia, additional, Ekin, Chris, additional, Evangelopoulos, Dimitrios, additional, Faraway, Rupert, additional, Fearns, Antony, additional, Ferron, Aaron, additional, Fidanis, Efthymios, additional, Fitz, Dan, additional, Fleming, James, additional, Frampton, Daniel, additional, Frederico, Bruno, additional, Gaiba, Alessandra, additional, Gait, Anthony, additional, Gamblin, Steve, additional, Gärtner, Kathleen, additional, Gaul, Liam, additional, Golding, Helen M., additional, Goldman, Jacki, additional, Goldstone, Robert, additional, Gomez Dominguez, Belen, additional, Gong, Hui, additional, Grant, Paul R., additional, Greco, Maria, additional, Grobler, Mariana, additional, Guedan, Anabel, additional, Gutierrez, Maximiliano G., additional, Hackett, Fiona, additional, Hall, Ross, additional, Halldorsson, Steinar, additional, Harris, Suzanne, additional, Hashim, Sugera, additional, Hatipoglu, Emine, additional, Healy, Lyn, additional, Heaney, Judith, additional, Herbst, Susanne, additional, Hewitt, Graeme, additional, Higgins, Theresa, additional, Hindmarsh, Steve, additional, Hirani, Rajnika, additional, Hope, Joshua, additional, Horton, Elizabeth, additional, Hoskins, Beth, additional, Howell, Michael, additional, Howitt, Louise, additional, Hoyle, Jacqueline, additional, Htun, Mint R., additional, Hubank, Michael, additional, Huerga Encabo, Hector, additional, Hughes, Deborah, additional, Hughes, Jane, additional, Huseynova, Almaz, additional, Hwang, Ming-Shih, additional, Instrell, Rachael, additional, Jackson, Deborah, additional, Jamal-Hanjani, Mariam, additional, Jenkins, Lucy, additional, Jiang, Ming, additional, Johnson, Mark, additional, Jones, Leigh, additional, Kanu, Nnennaya, additional, Kassiotis, George, additional, Kelly, Gavin, additional, Kiely, Louise, additional, Teixeira, Anastacio King Spert, additional, Kirk, Stuart, additional, Kjaer, Svend, additional, Knuepfer, Ellen, additional, Komarov, Nikita, additional, Kotzampaltiris, Paul, additional, Kousis, Konstantinos, additional, Krylova, Tammy, additional, Kucharska, Ania, additional, Labrum, Robyn, additional, Lambe, Catherine, additional, Lappin, Michelle, additional, Lee, Stacey-Ann, additional, Levett, Andrew, additional, Levett, Lisa, additional, Levi, Marcel, additional, Liu, Hon Wing, additional, Loughlin, Sam, additional, Lu, Wei-Ting, additional, MacRae, James I., additional, Madoo, Akshay, additional, Marczak, Julie A., additional, Martensson, Mimmi, additional, Martinez, Thomas, additional, Marzook, Bishara, additional, Matthews, John, additional, Matz, Joachim M., additional, McCall, Samuel, additional, McCoy, Laura E., additional, McKay, Fiona, additional, McNamara, Edel C., additional, Minutti, Carlos M., additional, Mistry, Gita, additional, Molina-Arcas, Miriam, additional, Montaner, Beatriz, additional, Montgomery, Kylie, additional, Moore, Catherine, additional, Moore, David, additional, Moraiti, Anastasia, additional, Moreira-Teixeira, Lucia, additional, Mukherjee, Joyita, additional, Naceur-Lombardelli, Cristina, additional, Nelson, Aileen, additional, Nicod, Jerome, additional, Nightingale, Luke, additional, Nofal, Stephanie, additional, Nurse, Paul, additional, Nutan, Savita, additional, Oedekoven, Caroline, additional, O'Garra, Anne, additional, O'Leary, Jean D., additional, Olsen, Jessica, additional, O'Neill, Olga, additional, O'Reilly, Nicola, additional, Suarez, Paula Ordonez, additional, Osborne, Neil, additional, Pabari, Amar, additional, Pajak, Aleksandra, additional, Papayannopoulos, Venizelos, additional, Paraskevopoulou, Stavroula M, additional, Patel, Namita, additional, Patel, Yogen, additional, Paun, Oana, additional, Peat, Nigel, additional, Peces-Barba Castano, Laura, additional, Caballero, Ana Perez, additional, Perez-Lloret, Jimena, additional, Perrault, Magali S., additional, Perrin, Abigail, additional, Poh, Roy, additional, Poirier, Enzo Z., additional, Polke, James M., additional, Pollitt, Marc, additional, Prieto-Godino, Lucia, additional, Proust, Alize, additional, Puvirajasinghe, Clinda, additional, Queval, Christophe, additional, Ramachandran, Vijaya, additional, Ramaprasad, Abhinay, additional, Ratcliffe, Peter, additional, Reed, Laura, additional, Reis e Sousa, Caetano, additional, Richardson, Kayleigh, additional, Ridewood, Sophie, additional, Roberts, Fiona, additional, Roberts, Rowenna, additional, Rodgers, Angela, additional, Romero Clavijo, Pablo, additional, Rosa, Annachiara, additional, Rossi, Alice, additional, Roustan, Chloe, additional, Rowan, Andrew, additional, Sahai, Erik, additional, Sait, Aaron, additional, Sala, Katarzyna, additional, Sanchez, Emilie, additional, Sanderson, Theo, additional, Santucci, Pierre, additional, Sardar, Fatima, additional, Sateriale, Adam, additional, Saunders, Jill A., additional, Sawyer, Chelsea, additional, Schlott, Anja, additional, Schweighoffer, Edina, additional, Segura-Bayona, Sandra, additional, Shah Punatar, Rajvee, additional, Shahmanesh, Maryam, additional, Shaw, Joe, additional, Silva Dos Santos, Mariana, additional, Silvestre, Margaux, additional, Singer, Matthew, additional, Snell, Daniel M., additional, Song, Ok-Ryul, additional, Spyer, Moira J., additional, Steel, Louisa, additional, Strange, Amy, additional, Sullivan, Adrienne E., additional, Tan, Michele S.Y., additional, Tautz-Davis, Zoe H., additional, Taylor, Effie, additional, Taylor, Gunes, additional, Taylor, Harriet B., additional, Taylor-Beadling, Alison, additional, Teixeira Subtil, Fernanda, additional, Terré Torras, Berta, additional, Toolan-Kerr, Patrick, additional, Torelli, Francesca, additional, Toteva, Tea, additional, Treeck, Moritz, additional, Trojer, Hadija, additional, Tsai, Ming-Han C., additional, Turner, James M.A., additional, Turner, Melanie, additional, Ule, Jernej, additional, Ulferts, Rachel, additional, Vanloo, Sharon P., additional, Veeriah, Selvaraju, additional, Venkatesan, Subramanian, additional, Vousden, Karen, additional, Wack, Andreas, additional, Walder, Claire, additional, Walker, Philip A., additional, Wang, Yiran, additional, Ward, Sophia, additional, Wenman, Catharina, additional, Williams, Luke, additional, Williams, Matthew J., additional, Keong Wong, Wai, additional, Wright, Joshua, additional, Wu, Mary, additional, Wynne, Lauren, additional, Xiang, Zheng, additional, Yap, Melvyn, additional, Zagalak, Julian A., additional, Zecchin, Davide, additional, Zillwood, Rachel, additional, Carthiyaniamma, Santhakumari, additional, DeTisi, Jane, additional, Dick, Julie, additional, Hill, Andrea, additional, Kipper, Karin, additional, Kullar, Birinder, additional, Norris, Sarah, additional, Rugg-Gunn, Fergus, additional, Salvatierra, Rebecca, additional, Shaya, Gabriel, additional, Sloan, Astrid, additional, Singh, Priyanka, additional, Varley, James, additional, and Whatley, Ben, additional

Published
2021
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18. Scalable and robust SARS-CoV-2 testing in an academic center

Author

Aitken, Jim, Ambrose, Karen, Barrell, Sam, Beale, Rupert, Bineva-Todd, Ganka, Biswas, Dhruva, Byrne, Richard, Caidan, Simon, Cherepanov, Peter, Churchward, Laura, Clark, Graham, Crawford, Margaret, Cubitt, Laura, Dearing, Vicky, Earl, Christopher, Edwards, Amelia, Ekin, Chris, Fidanis, Efthymios, Gaiba, Alessandra, Gamblin, Steve, Gandhi, Sonia, Goldman, Jacki, Goldstone, Robert, Grant, Paul R., Greco, Maria, Heaney, Judith, Hindmarsh, Steve, Houlihan, Catherine F., Howell, Michael, Hubank, Michael, Hughes, Deborah, Instrell, Rachael, Jackson, Deborah, Jamal-Hanjani, Mariam, Jiang, Ming, Johnson, Mark, Jones, Leigh, Kanu, Nnennaya, Kassiotis, George, Kirk, Stuart, Kjaer, Svend, Levett, Andrew, Levett, Lisa, Levi, Marcel, Lu, Wei-Ting, MacRae, James I., Matthews, John, McCoy, Laura E., Moore, Catherine, Moore, David, Nastouli, Eleni, Nicod, Jerome, Nightingale, Luke, Olsen, Jessica, O’Reilly, Nicola, Pabari, Amar, Papayannopoulos, Venizelos, Patel, Namita, Peat, Nigel, Pollitt, Marc, Ratcliffe, Peter, Reis e Sousa, Caetano, Rosa, Annachiara, Rosenthal, Rachel, Roustan, Chloe, Rowan, Andrew, Shin, Gee Yen, Snell, Daniel M., Song, Ok-Ryul, Spyer, Moira J., Strange, Amy, Swanton, Charles, Turner, James M. A., Turner, Melanie, Wack, Andreas, Walker, Philip A., Ward, Sophia, Wong, Wai Keong, Wright, Joshua, Wu, Mary, Allen, Zoe, Ambler, Rachel, Ashton, Emma, Avola, Alida, Balakrishnan, Samutheswari, Barns-Jenkins, Caitlin, Barr, Genevieve, Basu, Souradeep, Beesley, Clare, Bhardwaj, Nisha, Bibi, Shahnaz, Blackman, Michael J., Bonnet, Dominique, Bowker, Faye, Broncel, Malgorzata, Brooks, Claire, Buck, Michael D., Buckton, Andrew, Budd, Timothy, Burrell, Alana, Busby, Louise, Bussi, Claudio, Butterworth, Simon, Byrne, Fiona, Campbell, Joanna, Canton, Johnathan, Cardoso, Ana, Carter, Nick, Carvalho, Luiz, Carzaniga, Raffaella, Chandler, Natalie, Chen, Qu, Clayton, Bobbi, Gigli, Clementina Cobolli, Collins, Zena, Cottrell, Sally, Cullup, Tom, Davies, Heledd, Davis, Patrick, Davison, Dara, Debaisieux, Solene, Diaz-Romero, Monica, Dibbs, Alison, Diring, Jessica, Driscoll, Paul C., D’Avola, Annalisa, Evangelopoulos, Dimitrios, Faraway, Rupert, Fearns, Antony, Ferron, Aaron, Dan Fitz, Fleming, James, Frederico, Bruno, Gait, Anthony, Gaul, Liam, Golding, Helen M., Gomez Dominguez, Belen, Gong, Hui, Grobler, Mariana, Guedan, Anabel, Gutierrez, Maximiliano G., Hackett, Fiona, Hall, Ross, Halldorsson, Steinar, Harris, Suzanne, Hashim, Sugera, Healy, Lyn, Herbst, Susanne, Hewitt, Graeme, Higgins, Theresa, Hirani, Rajnika, Hope, Joshua, Horton, Elizabeth, Hoskins, Beth, Howitt, Louise, Hoyle, Jacqueline, Htun, Mint R., Huerga Encabo, Hector, Hughes, Jane, Huseynova, Almaz, Hwang, Ming-Shih, Jenkins, Lucy, Kiely, Louise, King Spert Teixeira, Anastacio, Knuepfer, Ellen, Komarov, Nikita, Kotzampaltiris, Paul, Kousis, Konstantinos, Krylova, Tammy, Kucharska, Ania, Labrum, Robyn, Lambe, Catherine, Lappin, Michelle, Lee, Stacey-Ann, Liu, Hon Wing, Loughlin, Sam, Madoo, Akshay, Marczak, Julie A., Martensson, Mimmi, Martinez, Thomas, Marzook, Bishara, Matz, Joachim M., McCall, Samuel, McKay, Fiona, McNamara, Edel C., Minutti, Carlos M., Mistry, Gita, Molina-Arcas, Miriam, Montaner, Beatriz, Montgomery, Kylie, Moraiti, Anastasia, Moreira-Teixeira, Lucia, Mukherjee, Joyita, Naceur-Lombardelli, Cristina, Nelson, Aileen, Nofal, Stephanie, Nurse, Paul, Nutan, Savita, Oedekoven, Caroline, O’Garra, Anne, O’Leary, Jean D., O’Neill, Olga, Suarez, Paula Ordonez, Osborne, Neil, Pajak, Aleksandra, Patel, Yogen, Paun, Oana, Peces-Barba Castano, Laura, Perez Caballero, Ana, Perez-Lloret, Jimena, Perrault, Magali S., Perrin, Abigail, Poh, Roy, Poirier, Enzo Z., Polke, James M., Prieto-Godino, Lucia, Proust, Alize, Puvirajasinghe, Clinda, Queval, Christophe, Ramachandran, Vijaya, Ramaprasad, Abhinay, Reed, Laura, Richardson, Kayleigh, Ridewood, Sophie, Roberts, Fiona, Roberts, Rowenna, Rodgers, Angela, Clavijo, Pablo Romero, Rossi, Alice, Sahai, Erik, Sait, Aaron, Sala, Katarzyna, Sanderson, Theo, Santucci, Pierre, Sardar, Fatima, Sateriale, Adam, Saunders, Jill A., Sawyer, Chelsea, Schlott, Anja, Schweighoffer, Edina, Segura-Bayona, Sandra, Shah Punatar, Rajvee, Shaw, Joe, Silva Dos Santos, Mariana, Silvestre, Margaux, Singer, Matthew, Steel, Louisa, Sullivan, Adrienne E., Tan, Michele S. Y., Tautz-Davis, Zoe H., Taylor, Effie, Taylor, Gunes, Taylor, Harriet B., Taylor-Beadling, Alison, Teixeira Subtil, Fernanda, Terré Torras, Berta, Toolan-Kerr, Patrick, Torelli, Francesca, Toteva, Tea, Treeck, Moritz, Trojer, Hadija, Tsai, Ming-Han C., Ule, Jernej, Ulferts, Rachel, Vanloo, Sharon P., Veeriah, Selvaraju, Venkatesan, Subramanian, Vousden, Karen, Walder, Claire, Wang, Yiran, Wenman, Catharina, Williams, Luke, Williams, Matthew J., Wynne, Lauren, Xiang, Zheng, Yap, Melvyn, Zagalak, Julian A., Zecchin, Davide, and Zillwood, Rachel

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Crick COVID-19 Consortium, Biomedical Engineering, Bioengineering, CORONAVIRUS, medicine.disease_cause, Applied Microbiology and Biotechnology, medicine, Medical Laboratory Science, Humans, Royaume uni, Coronavirus, Reino unido, Science & Technology, business.industry, Clinical Laboratory Techniques, Reverse Transcriptase Polymerase Chain Reaction, Academies and Institutes, Virology, United Kingdom, Europe, Biotechnology & Applied Microbiology, Molecular Medicine, business, Coronavirus Infections, Life Sciences & Biomedicine, Biotechnology, PNEUMONIA OUTBREAK
Published
2020

19. The regulation of CDK activity by cyclins

Author

Basu, Souradeep, Nurse, Paul, Freemont, Paul, Cancer Research UK, Medical Research Council (Great Britain), Wellcome Trust (London, England), Wellcome Trust Grant to Paul Nurse, and The Lord Leonard and Lady Estelle Wolfson Foundation

Abstract

In eukaryotes, the two major cell cycle events of DNA replication and chromosome segregation are directed by Cyclin Dependent Kinases (CDKs) in combination with G1/S cyclins (S-CDK) and G2/M cyclins (M-CDK), respectively. It is still unclear what differentiates S-CDK activity from M-CDK activity, and how much functional redundancy exists between cyclin-CDK complexes. Here the fission yeast G1/S cyclin-CDK complex, Cig2-Cdc2, is used to study S-CDK. It is shown that S-CDK is capable of achieving high levels of CDK activity, but is incapable of executing mitosis. However, deletion of Protein Phosphatase 1 (PP1) allows for mitotic progression, and is therefore responsible for restricting S-CDK from executing mitosis. Substrates at the yeast centrosome equivalent, the spindle pole body (SPB), are phosphorylated poorly by S-CDK. Consistent with this idea, removal of PP1 at the SPB alone allows S-CDK to drive mitosis. Phosphoproteomic analysis then shows that S-CDK and M-CDK have subtly different in vivo CDK substrate preferences, but that the majority of substrates experience S-CDK and M-CDK activity equally. Using a CDK mutant that does not need cyclin binding for activity, evidence is presented suggesting that generic CDK activity without cyclins is sufficient for S-phase, but that cyclin-associated CDK activity is required for mitosis. In pursuit of why cyclins are essential for mitosis, the substrate docking region of the mitotic cyclin Cdc13 is mutated. The mutation of this region does not affect Cdc13-dependent S-phase progression, but cells fail to execute mitosis. Mutant Cdc13 is unable to localise correctly to the interphase SPB, and phosphoproteomic analysis suggests that this defect causes reduced CDK substrate phosphorylation at the SPB, preventing mitosis. These data are consistent with the idea that cyclins regulate CDK localisation at mitosis to influence CDK substrate selection, and suggests that correctly regulated CDK activity across cellular compartments is needed to execute mitosis. Open Access

Published
2020
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21. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers

Author

Houlihan, Catherine F, primary, Vora, Nina, additional, Byrne, Thomas, additional, Lewer, Dan, additional, Kelly, Gavin, additional, Heaney, Judith, additional, Gandhi, Sonia, additional, Spyer, Moira J, additional, Beale, Rupert, additional, Cherepanov, Peter, additional, Moore, David, additional, Gilson, Richard, additional, Gamblin, Steve, additional, Kassiotis, George, additional, McCoy, Laura E, additional, Swanton, Charles, additional, Hayward, Andrew, additional, Nastouli, Eleni, additional, Aitken, Jim, additional, Allen, Zoe, additional, Ambler, Rachel, additional, Ambrose, Karen, additional, Ashton, Emma, additional, Avola, Alida, additional, Balakrishnan, Samutheswari, additional, Barns-Jenkins, Caitlin, additional, Barr, Genevieve, additional, Barrell, Sam, additional, Basu, Souradeep, additional, Beesley, Clare, additional, Bhardwaj, Nisha, additional, Bibi, Shahnaz, additional, Bineva-Todd, Ganka, additional, Biswas, Dhruva, additional, Blackman, Michael J, additional, Bonnet, Dominique, additional, Bowker, Faye, additional, Broncel, Malgorzata, additional, Brooks, Claire, additional, Buck, Michael D, additional, Buckton, Andrew, additional, Budd, Timothy, additional, Burrell, Alana, additional, Busby, Louise, additional, Bussi, Claudio, additional, Butterworth, Simon, additional, Byrne, Fiona, additional, Byrne, Richard, additional, Caidan, Simon, additional, Campbell, Joanna, additional, Canton, Johnathan, additional, Cardoso, Ana, additional, Carter, Nick, additional, Carvalho, Luiz, additional, Carzaniga, Raffaella, additional, Chandler, Natalie, additional, Chen, Qu, additional, Churchward, Laura, additional, Clark, Graham, additional, Clayton, Bobbi, additional, Cobolli Gigli, Clementina, additional, Collins, Zena, additional, Cottrell, Sally, additional, Crawford, Margaret, additional, Cubitt, Laura, additional, Cullup, Tom, additional, Davies, Heledd, additional, Davis, Patrick, additional, Davison, Dara, additional, D'Avola, Annalisa, additional, Dearing, Vicky, additional, Debaisieux, Solene, additional, Diaz-Romero, Monica, additional, Dibbs, Alison, additional, Diring, Jessica, additional, Driscoll, Paul C, additional, Earl, Christopher, additional, Edwards, Amelia, additional, Ekin, Chris, additional, Evangelopoulos, Dimitrios, additional, Faraway, Rupert, additional, Fearns, Antony, additional, Ferron, Aaron, additional, Fidanis, Efthymios, additional, Fitz, Dan, additional, Fleming, James, additional, Frederico, Bruno, additional, Gaiba, Alessandra, additional, Gait, Anthony, additional, Gaul, Liam, additional, Golding, Helen M, additional, Goldman, Jacki, additional, Goldstone, Robert, additional, Gomez Dominguez, Belen, additional, Gong, Hui, additional, Grant, Paul R, additional, Greco, Maria, additional, Grobler, Mariana, additional, Guedan, Anabel, additional, Gutierrez, Maximiliano G, additional, Hackett, Fiona, additional, Hall, Ross, additional, Halldorsson, Steinar, additional, Harris, Suzanne, additional, Hashim, Sugera, additional, Healy, Lyn, additional, Herbst, Susanne, additional, Hewitt, Graeme, additional, Higgins, Theresa, additional, Hindmarsh, Steve, additional, Hirani, Rajnika, additional, Hope, Joshua, additional, Horton, Elizabeth, additional, Hoskins, Beth, additional, Houlihan, Catherine F, additional, Howell, Michael, additional, Howitt, Louise, additional, Hoyle, Jacqueline, additional, Htun, Mint R, additional, Hubank, Michael, additional, Huerga Encabo, Hector, additional, Hughes, Deborah, additional, Hughes, Jane, additional, Huseynova, Almaz, additional, Hwang, Ming-Shih, additional, Instrell, Rachael, additional, Jackson, Deborah, additional, Jamal-Hanjani, Mariam, additional, Jenkins, Lucy, additional, Jiang, Ming, additional, Johnson, Mark, additional, Jones, Leigh, additional, Kanu, Nnennaya, additional, Kiely, Louise, additional, King Spert Teixeira, Anastacio, additional, Kirk, Stuart, additional, Kjaer, Svend, additional, Knuepfer, Ellen, additional, Komarov, Nikita, additional, Kotzampaltiris, Paul, additional, Kousis, Konstantinos, additional, Krylova, Tammy, additional, Kucharska, Ania, additional, Labrum, Robyn, additional, Lambe, Catherine, additional, Lappin, Michelle, additional, Lee, Stacey-Ann, additional, Levett, Andrew, additional, Levett, Lisa, additional, Levi, Marcel, additional, Liu, Hon-Wing, additional, Loughlin, Sam, additional, Lu, Wei-Ting, additional, MacRae, James I, additional, Madoo, Akshay, additional, Marczak, Julie A, additional, Martensson, Mimmi, additional, Martinez, Thomas, additional, Marzook, Bishara, additional, Matthews, John, additional, Matz, Joachim M, additional, McCall, Samuel, additional, McKay, Fiona, additional, McNamara, Edel C, additional, Minutti, Carlos M, additional, Mistry, Gita, additional, Molina-Arcas, Miriam, additional, Montaner, Beatriz, additional, Montgomery, Kylie, additional, Moore, Catherine, additional, Moraiti, Anastasia, additional, Moreira-Teixeira, Lucia, additional, Mukherjee, Joyita, additional, Naceur-Lombardelli, Cristina, additional, Nelson, Aileen, additional, Nicod, Jerome, additional, Nightingale, Luke, additional, Nofal, Stephanie, additional, Nurse, Paul, additional, Nutan, Savita, additional, Oedekoven, Caroline, additional, O'Garra, Anne, additional, O'Leary, Jean D, additional, Olsen, Jessica, additional, O'Neill, Olga, additional, Ordonez Suarez, Paula, additional, O'Reilly, Nicola, additional, Osborne, Neil, additional, Pabari, Amar, additional, Pajak, Aleksandra, additional, Papayannopoulos, Venizelos, additional, Patel, Namita, additional, Patel, Yogen, additional, Paun, Oana, additional, Peat, Nigel, additional, Peces-Barba Castano, Laura, additional, Perez Caballero, Ana, additional, Perez-Lloret, Jimena, additional, Perrault, Magali S, additional, Perrin, Abigail, additional, Poh, Roy, additional, Poirier, Enzo Z, additional, Polke, James M, additional, Pollitt, Marc, additional, Prieto-Godino, Lucia, additional, Proust, Alize, additional, Shah Punatar, Rajvee, additional, Puvirajasinghe, Clinda, additional, Queval, Christophe, additional, Ramachandran, Vijaya, additional, Ramaprasad, Abhinay, additional, Ratcliffe, Peter, additional, Reed, Laura, additional, Reis e Sousa, Caetano, additional, Richardson, Kayleigh, additional, Ridewood, Sophie, additional, Roberts, Rowenna, additional, Rodgers, Angela, additional, Romero Clavijo, Pablo, additional, Rosa, Annachiara, additional, Rossi, Alice, additional, Roustan, Chloe, additional, Rowan, Andrew, additional, Sahai, Erik, additional, Sait, Aaron, additional, Sala, Katarzyna, additional, Sanderson, Theo, additional, Santucci, Pierre, additional, Sardar, Fatima, additional, Sateriale, Adam, additional, Saunders, Jill A, additional, Sawyer, Chelsea, additional, Schlott, Anja, additional, Schweighoffer, Edina, additional, Segura-Bayona, Sandra, additional, Shaw, Joe, additional, Shin, Gee Yen, additional, Silva Dos Santos, Mariana, additional, Silvestre, Margaux, additional, Singer, Matthew, additional, Snell, Daniel M, additional, Song, Ok-Ryul, additional, Steel, Louisa, additional, Strange, Amy, additional, Sullivan, Adrienne E, additional, Tan, Michele SY, additional, Tautz-Davis, Zoe H, additional, Taylor, Effie, additional, Taylor, Gunes, additional, Taylor, Harriet B, additional, Taylor-Beadling, Alison, additional, Teixeira Subtil, Fernanda, additional, Terré Torras, Berta, additional, Toolan-Kerr, Patrick, additional, Torelli, Francesca, additional, Toteva, Tea, additional, Treeck, Moritz, additional, Trojer, Hadija, additional, Tsai, Ming-Han C, additional, Turner, James MA, additional, Turner, Melanie, additional, Ule, Jernej, additional, Ulferts, Rachel, additional, Vanloo, Sharon P, additional, Veeriah, Selvaraju, additional, Venkatesan, Subramanian, additional, Vousden, Karen, additional, Wack, Andreas, additional, Walder, Claire, additional, Walker, Philip A, additional, Wang, Yiran, additional, Ward, Sophia, additional, Wenman, Catharina, additional, Wiliams, Luke, additional, Williams, Matthew J, additional, Wong, Wai Keong, additional, Wright, Joshua, additional, Wu, Mary, additional, Wynne, Lauren, additional, Xiang, Zheng, additional, Yap, Melvyn, additional, Zagalak, Julian A, additional, Zecchin, Davide, additional, Zillwood, Rachel, additional, Matthews, Rebecca, additional, Severn, Abigail, additional, Adam, Sajida, additional, Enfield, Louise, additional, McBride, Angela, additional, Gärtner, Kathleen, additional, Edwards, Sarah, additional, Lorencatto, Fabiana, additional, Michie, Susan, additional, Manley, Ed, additional, Shahmanesh, Maryam, additional, Lukha, Hinal, additional, Prymas, Paulina, additional, McBain, Hazel, additional, Shortman, Robert, additional, Wood, Leigh, additional, Davies, Claudia, additional, Williams, Bethany, additional, Ng, Kevin W, additional, Cornish, Georgina H, additional, Faulkner, Nikhil, additional, Riddell, Andrew, additional, Hobson, Philip, additional, Agua-Doce, Ana, additional, Bartolovic, Kerol, additional, Russell, Emma, additional, Carr, Lotte, additional, Sanchez, Emilie, additional, Frampton, Daniel, additional, Byott, Matthew, additional, Paraskevopoulou, Stavroula M, additional, Crayton, Elise, additional, Meyer, Carly, additional, Gkouleli, Triantafylia, additional, Stoltenberg, Andrea, additional, Ranieri, Veronica, additional, Byrne, Tom, additional, Roberts, Fiona, additional, and Hatipoglu, Emine, additional

Published
2020
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25. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/ nsp10 exoribonuclease.

Author

Canal, Berta, McClure, Allison W., Curran, Joseph F., Wu, Mary, Ulferts, Rachel, Weissmann, Florian, Jingkun Zeng, Bertolin, Agustina P., Milligan, Jennifer C., Basu, Souradeep, Drury, Lucy S., Deegan, Tom D., Fujisawa, Ryo, Roberts, Emma L., Basier, Clovis, Labib, Karim, Beale, Rupert, Howell, Michael, and Diffley, John F. X.

Subjects
SARS-CoV-2, SMALL molecules, COVID-19 treatment, COVID-19, VIRAL genomes
Abstract

SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is an urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with highthroughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19. [ABSTRACT FROM AUTHOR]

Published
2021
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27. Trimethoxyphenyl (TMP) as a Useful Auxiliary for in situ Formation and Reaction of Aryl(TMP)iodonium Salts: Synthesis of Diaryl Ethers.

Author

Gallagher, Rory T., Basu, Souradeep, and Stuart, David R.

Subjects
*IODONIUM salts, *ETHER synthesis, *PHENOL, *ARYLATION, *CHEMOSELECTIVITY, *ARYL iodides, *ORGANOLITHIUM compounds
Abstract

Herein, we describe a synthetic approach for arylation that exploits the in situ formation and reaction of an unsymmetrical diaryliodonium salt. In this way, aryl iodides are used as reagents in a metal‐free reaction with phenols, and a trimethoxyphenyl (TMP) group is used as a "dummy" group to facilitate transfer of a wide range of aryl moieties. The scope of aryl electrophiles and phenol nucleophiles is broad (>30 examples) and the yields are high (52–95%, 80% avg.). One‐pot coupling reactions avoid the synthesis of diaryliodonium salts and provide opportunities for sequential reactions and novel chemoselectivity. [ABSTRACT FROM AUTHOR]

Published
2020
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