Search

Your search keyword '"Wilkins, Laura"' showing total 18 results
Start Over Author "Wilkins, Laura"
18 results on '"Wilkins, Laura"'

2. Bioorthogonal nanomaterials to probe adhesive protein function

Author

Wilkins, Laura Elizabeth

Subjects
540, QD Chemistry, QP Physiology
Abstract

Tools to understand the mechanisms of protein binding to cell surface proteins are of interest to enable the manipulation of such proteins, such as for therapy and drug delivery. In particular, bioorthogonal techniques are of interest as they can be used to probe protein structure and function in their native environment with minimal structural perturbation, as described in Chapter 1. This work seeks to develop such bioorthogonally-designed materials (polymers and nanoparticles) in order to study adhesive proteins. In Chapter 2, using controlled radical polymerisation and "click"-like chemistries, doubly-functionalised glycopolymers with sequential variation in carbohydrate density, side chain length and secondary functionality were synthesized to probe the binding activity of an adhesive pathogenic toxin (Vibrio cholerae toxin subunit B). This revealed a new approach whereby sterically large secondary units enabled selectivity towards a toxin to be introduced. In chapter 3, a small (< 5 nm diameter) gold nanoparticle (AuNP) scaffold was used as the basis for the development of a dendrimeric ice binding protein (antifreeze protein type III). Two different bioorthogonal immobilization strategies were developed to probe AFP capture to NP surfaces. Optimum AFP activity was observed only for covalent SNAP-tag conjugates. Furthermore, this was critically compared to a fullysynthetic AFP mimic; poly(vinyl alcohol) coated gold nanoparticles. Chapter 4 reports a detailed investigation into the function of adhesive protein fibres from an insect pathogen, using the nanoparticle tools developed here. Recombinant his-tagged fibres were immobilized and evaluated for whole-cell binding to a range of cell lines, and also lipid and glycan arrays. Furthermore, proteomics used to identify insect and mammalian cell protein targets. This resulted in the first ever description of Pvc13 tail fibre protein function, which may help elucidate its pathogenicity and a potential application in drug delivery. In summary, novel nanomaterials were developed in order to probe adhesive protein structure and function. These materials must be delicately designed to avoid an impact on native protein function, and to exploit the material properties to their full effect.

Published
2018

7. The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers

Author

Lumley, Sheila F, Wei, Jia, O’Donnell, Denise, Stoesser, Nicole E, Matthews, Philippa C, Howarth, Alison, Hatch, Stephanie B, Marsden, Brian D, Cox, Stuart, James, Tim, Peck, Liam J, Ritter, Thomas G, de Toledo, Zoe, Cornall, Richard J, Jones, E Yvonne, Stuart, David I, Screaton, Gavin, Ebner, Daniel, Hoosdally, Sarah, Crook, Derrick W, Conlon, Christopher P, Pouwels, Koen B, Walker, A Sarah, Peto, Tim E A, Walker, Timothy M, Jeffery, Katie, Eyre, David W, Abbott, Molly, Abhari, Roxanna, Abuelgasim, Hibatullah, Ahmed-Firani, Tariq, Alhussni, Ahmed, Argles, Isobel, Ashworth, Rebecca, Back, Francesca, Black, Susannah, Brennan, Isabelle, Cansdale, Lottie, Chakravorty, Triya, Choudhury, Zahra, Clay, Helen, Conway-Jones, Rebecca, Curtis, Aisling, Cutteridge, Joseph, Danbury, Hannah, Davies, Hettie, Denly, Lucy, Dequaire, Julie, Dimitrov, Stoyan, Dunlop, Ella, Dunn, Polly, East, Cameron, Eastwood, Ben, Edwardes, Chantal, Evans, Meirian, Fields, Charlotte, Flaherty, Sarah, Foord, Thomas, Freer, Rosie, Fuchs, Hannah, Grassam-Rowe, Alexander, Greenan-Barrett, Lewis, Gunnell, James, Harries, Callum, Harris, Edward, Hatton, Elizabeth, Hennessy, Conor, Holland, Christian, Holloway, Ben, Howgego, Gregory, Barnham, Isaac Jarratt, Johnson, Síle, Johnson, Thomas, Johnstone, Daniela, Jurdon, Rebecca, Kelly, Gabriella, Kerneis, Sven, Khulusi, Beinn, Killen, Annabel, Kourdov, Stefan, Kumarendran, Mary, Laurenson-Schafer, Hannah, Lawrence, Ruby, Lee, Charlotte, Livingstone, Angus, Lynch, Rosie, Madsen, Tara, Manji, Ali, Marsh, James, Mason, Chris, Mccance, Angus, Mcgivern, Euan, Mckinlay, Ailsa, Mighiu, Alexandra, Millar, Lancelot, Mohamed, Yethrib, Motohashi, Kenzo, Myat, San, Nezhentsev, Andrey, O’Byrne, Katherine, Okuwoga, Temitope, Oliver, Madeleine, Pattenden, Saxon, Perera, Vimukthi, Petit, Yva, Pickles, Florence, Pikoula, Maria, Randhawa, Govind, Ravi, Krupa, Reed, Lara, Rigler, Caitlin, Robinson, Charlotte, Rothwell, Evie, Santos-Paulo, Stephanie, Savva, Constantinos, Scharmeli, Alice, Scott, Samuel, Shabir, Zamin, Sharma, Ishta, Sheehan, Remarez, Shibu, Afrah, Somanathan, Arun, Sussmes, Samuel, Sweeney, Owen, Swift, Emily, Tadikamalla, Gayatri, Tamblyn, Morwenna, Taylor, Adan, Naudé, Rebecca Te Water, Thomas, Sarah, Thompson, Connor, Till, Lottie, Toward, Ross, Virgo, Charis, Vorley, Imogen, Waite, Seren, Ward, Harry, Ward, Jocelyn, Watson, Adam, Watson, Lily, Wedlich, Matthew, Wilkins, Laura, Wilson, Jack, Wilson, Joseph, Wong, William, Young, Rebecca, Doherty, George, Kavanagh, James, Chau, Kevin K, Fowler, Philip W, Swann, Jeremy, Volk, Denis, Yang-Turner, Fan, Skelly, Donal, Karpe, Fredrik, Neville, Matt J, Ferreira, Lucas Martins, Christott, Thomas, Rodger, Gillian, Pickford, Hayleah, Cameron, Sarah, Tamblin-Hopper, Phoebe, Amini, Ali, Andersson, Monique, Anson, Karen, Aston, Lisa, Axten, David, Barot, Simran, Bellinger, Trisha, Bialek, Adrian, Bodo, Noemi, Brent, Andrew, Campbell, Mark, Cox, Vanessa, Cronin, Tammy, Davies, Timothy, Deales, Alessio, Downs, Louise, Drennan, Philip, Dudareva, Maria, Gates, Laura, Gates, Michelle, Georgiou, Dominique, Gergely, Bernadett, Holland, Louise, Jones, Nicola, Jones, Sarah, Kerr, Sharon, Lawson, Elaine, Looms, Stacy, Luciw, Michael, Martins, Diva, Mcknight, Mary, Mentzer, Alexander, Millard, Rebecca, Mitchell, Tracey, Morgan, Lisa, Morrow, Jordan, Mortimore, Emma, Mullins, Harriet, Nevard, Heather, O’Donnell, Anne-Marie, Patel, Kaisha, Peto, Leon, Philips, Jane, Ponting, Jessica, Ray, Roshni, Robles, Maria, Rughani, Sonam, Sande, Nellia, Shaw, Robert, Simons, Emma-Jane, Sims, Elizabeth, Smit, Kyla, Smith, Lucianne, Szczurkowska, Justyna, Thompson, Zoe, Turford, Rachel, Vilca, Kim, Vogt, Alexander, Warren, Fiona, Warren, Laura, Wharton, Vicki, Whitty, Alison, Woodley, Heather, Wozniak, Barbara, Young, Bernadette, Justice, Anita, Jesuthasan, Gerald, Wareing, Susan, Fadzillah, Nurul Huda Mohamad, Cann, Kathryn, Kirton, Richard, Sutton, Claire, Salvagno, Claudia, D’Amato, Gabriella, Pill, Gemma, Butcher, Lisa, Rylance-Knight, Lydia, Tabirao, Merline, Moroney, Ruth, Wright, Sarah, and Group, Oxford University Hospitals Staff Testing

Subjects
0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Health Personnel, Population, Antibodies, Viral, Immunoglobulin G, Serology, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Internal medicine, Correspondence, Credible interval, Major Article, Seroprevalence, Medicine, Humans, 030212 general & internal medicine, education, Survival analysis, Antibody, education.field_of_study, biology, business.industry, SARS-CoV-2, COVID-19, Bayes Theorem, Waning, Titer, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00290, Reinfection, Antibody Formation, biology.protein, Longitudinal, business
Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. Results Anti-spike IgG levels remained stably detected after a positive result, for example, in 94% (95% credibility interval [CrI] 91–96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% CrI 19–31) days post first polymerase chain reaction (PCR)-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titer, the mean estimated antibody half-life was 85 (95% CrI 81–90) days. Higher maximum observed anti-nucleocapsid titers were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity, and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. Conclusions SARS-CoV-2 anti-nucleocapsid antibodies wane within months and fall faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.

Published
2021

12. Multivalent Antimicrobial Polymer Nanoparticles Target Mycobacteria and Gram-Negative Bacteria by Distinct Mechanisms

Author

Richards, Sarah-Jane, Isufi, Klea, Wilkins, Laura E., Lipecki, Julia, Fullam, Elizabeth, and Gibson, Matthew I.

Abstract

Because of the emergence of antimicrobial resistance to traditional small-molecule drugs, cationic antimicrobial polymers are appealing targets. Mycobacterium tuberculosisis a particular problem, with multi- and total drug resistance spreading and more than a billion latent infections globally. This study reports nanoparticles bearing variable densities of poly(dimethylaminoethyl methacrylate) and the unexpected and distinct mechanisms of action this multivalent presentation imparts against Escherichia coliversus Mycobacterium smegmatis(model of M. tuberculosis), leading to killing or growth inhibition, respectively. A convergent “grafting to” synthetic strategy was used to assemble a 50-member nanoparticle library, and using a high-throughput screen identified that only the smallest (2 nm) particles were stable in both saline and complex cell media. Compared with the linear polymers, the nanoparticles displayed two- and eight-fold enhancements in antimicrobial activity against M. smegmatisand E. coli, respectively. Mechanistic studies demonstrated that the antimicrobial particles were bactericidal against E. colidue to rapid disruption of the cell membranes. Conversely, against M. smegmatisthe particles did not lyse the cell membrane but rather had a bacteriostatic effect. These results demonstrate that to develop new polymeric antituberculars the widely assumed, broad spectrum, membrane-disrupting mechanism of polycations must be re-evaluated. It is clear that synthetic nanomaterials can engage in more complex interactions with mycobacteria, which we hypothesize is due to the unique cell envelope at the surface of these bacteria.

Published
2024
Full Text
View/download PDF

16. Multivalent Presentation of Ice Recrystallization Inhibiting Polymers on Nanoparticles Retains Activity

Author

Stubbs, Christopher, Wilkins, Laura E., Fayter, Alice E. R, Walker, Marc, and Gibson, Matthew I.

Abstract

Poly(vinyl alcohol) (PVA) has emerged as the most potent mimic of antifreeze (glyco)proteins ice recrystallization inhibition (IRI) activity, despite its lack of structural similarities and flexible, rather than rigid, backbone. The precise spacing of hydroxyl groups is hypothesized to enable PVA to recognize the prism planes of ice but not the basal plane, due to hydroxyl pattern matching of the ice surface giving rise to the macroscopic activity. Here, well-defined PVA derived from reversible addition–fragmentation chain-transfer (RAFT) polymerization is immobilized onto gold nanoparticles to enable the impact of nanoscale assembly and confinement on the observed IRI activity. Unlike previous reports using star-branched or bottle-brush PVAs, the nanoparticle–PVA retains all IRI activity compared to polymers in solution. Evidence is presented to show that this is due to the low grafting densities on the particle surface meaning the chains are free to explore the ice faces, rather than being constrained as in star-branched polymers. These results demonstrate a route to develop more functional IRI’s and inclusion of metallic particle cores for imaging and associated applications in cryobiology.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results