Search

Your search keyword '"Guilliams, Tim"' showing total 27 results
Start Over Author "Guilliams, Tim"
27 results on '"Guilliams, Tim"'

5. Pathways for Academic Impact: Biased Towards Commercialisation?

Author

Guilliams, Tim

Abstract

Given the current economic climate it is important to maximise academic impact on society. Measures of academic impact have been dominated by the commercialisation of academic discoveries, thereby failing to capture the complete spectrum of academic activities that lead to societal impact. In fact, universities do not appear to act as a significant source of intellectual property and technology for private companies. It is therefore questionable to use commercialisation of academic discoveries as the main metric to measure impact. Thisarticle highlights the importance of a broader view when assessing knowledge exchange between universities and other sectors and the measurement of academic impact on society, hoping to move beyond commercialisation.

Published
2018
Full Text
View/download PDF

6. Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Author

El Turk, Farah, De Genst, Erwin, Guilliams, Tim, Fauvet, Bruno, Hejjaoui, Mirva, Di Trani, Justin, Chiki, Anass, Mittermaier, Anthony, Vendruscolo, Michele, Lashuel, Hilal A, Dobson, Christopher M, Vendruscolo, Michele [0000-0002-3616-1610], and Apollo - University of Cambridge Repository

Subjects
Binding Sites, single-domain antibody (sdAb, nuclear magnetic resonance (NMR), phosphorylation, Parkinson's disease, Brain, Parkinson Disease, Single-Domain Antibodies, nervous system diseases, isothermal titration calorimetry, nuclear magnetic resonance, α-synuclein, Parkinson’s disease, nanobody), Serine, alpha-Synuclein, surface plasmon resonance (SPR), Humans, Tyrosine, Autopsy, protein misfolding, isothermal titration calorimetry (ITC), Protein Processing, Post-Translational, surface plasmon resonance, Protein Binding
Abstract

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major modulators of its structure, function, degradation and toxicity. Among these PTMs, phosphorylation near the C-terminus at S129 has emerged as a dominant pathogenic modification as it is consistently observed to occur within the brain and cerebrospinal fluid (CSF) of post-mortem PD patients, and its level appears to correlate with disease progression. Phosphorylation at the neighboring tyrosine residue Y125 has also been shown to protect against α-synuclein toxicity in a Drosophila model of PD. In the present study we address the potential roles of C-terminal phosphorylation in modulating the interaction of α-synuclein with other protein partners, using a single domain antibody fragment (NbSyn87) that binds to the C-terminal region of α-synuclein with nanomolar affinity. The results reveal that phosphorylation at S129 has negligible effect on the binding affinity of NbSyn87 to α-synuclein while phosphorylation at Y125, only four residues away, decreases the binding affinity by a factor of 400. These findings show that, despite the fact that α-synuclein is intrinsically disordered in solution, selective phosphorylation can modulate significantly its interactions with other molecules, and suggest how this particular form of modification could play a key role in regulating the normal and aberrant function of α-synuclein.

Published
2018

8. Drug repurposing: progress, challenges and recommendations

Author

Pushpakom, Sudeep, primary, Iorio, Francesco, additional, Eyers, Patrick A., additional, Escott, K. Jane, additional, Hopper, Shirley, additional, Wells, Andrew, additional, Doig, Andrew, additional, Guilliams, Tim, additional, Latimer, Joanna, additional, McNamee, Christine, additional, Norris, Alan, additional, Sanseau, Philippe, additional, Cavalla, David, additional, and Pirmohamed, Munir, additional

Published
2018
Full Text
View/download PDF

10. Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Author

El Turk, Farah, primary, De Genst, Erwin, additional, Guilliams, Tim, additional, Fauvet, Bruno, additional, Hejjaoui, Mirva, additional, Di Trani, Justin, additional, Chiki, Anass, additional, Mittermaier, Anthony, additional, Vendruscolo, Michele, additional, Lashuel, Hilal A., additional, and Dobson, Christopher M., additional

Published
2018
Full Text
View/download PDF

12. Nanobodies raised against monomeric ɑ-synuclein inhibit fibril formation and destabilize toxic oligomeric species

Author

Iljina, Marija, primary, Hong, Liu, additional, Horrocks, Mathew H., additional, Ludtmann, Marthe H., additional, Choi, Minee L., additional, Hughes, Craig D., additional, Ruggeri, Francesco S., additional, Guilliams, Tim, additional, Buell, Alexander K., additional, Lee, Ji-Eun, additional, Gandhi, Sonia, additional, Lee, Steven F., additional, Bryant, Clare E., additional, Vendruscolo, Michele, additional, Knowles, Tuomas P. J., additional, Dobson, Christopher M., additional, De Genst, Erwin, additional, and Klenerman, David, additional

Published
2017
Full Text
View/download PDF

13. Understanding and predicting disease relationships through similarity fusion.

Author

Oerton, Erin, Bender, Andreas, Roberts, Ian, Lewis, Patrick S H, and Guilliams, Tim

Subjects
EPIDEMICS, FUSION (Phase transformation), POLYMER melting, THAWING, PHENOTYPIC plasticity
Abstract

Motivation Combining disease relationships across multiple biological levels could aid our understanding of common processes taking place in disease, potentially indicating opportunities for drug sharing. Here, we propose a similarity fusion approach which accounts for differences in information content between different data types, allowing combination of each data type in a balanced manner. Results We apply this method to six different types of biological data (ontological, phenotypic, literature co-occurrence, genetic association, gene expression and drug indication data) for 84 diseases to create a 'disease map': a network of diseases connected at one or more biological levels. As well as reconstructing known disease relationships, 15% of links in the disease map are novel links spanning traditional ontological classes, such as between psoriasis and inflammatory bowel disease. 62% of links in the disease map represent drug-sharing relationships, illustrating the relevance of the similarity fusion approach to the identification of potential therapeutic relationships. Availability and implementation Freely available under the MIT license at https://github.com/e-oerton/disease-similarity-fusion Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

15. Drug repurposing: progress, challenges and recommendations

Author

Pushpakom, Sudeep, Iorio, Francesco, Eyers, Patrick A., Escott, K. Jane, Hopper, Shirley, Wells, Andrew, Doig, Andrew, Guilliams, Tim, Latimer, Joanna, McNamee, Christine, Norris, Alan, Sanseau, Philippe, Cavalla, David, and Pirmohamed, Munir

Abstract

Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.

Published
2019
Full Text
View/download PDF

16. Nanobodies raised against monomeric α-synuclein inhibit fibril formation and destabilize toxic oligomeric species.

Author

Iljina, Marija, Liu Hong, Horrocks, Mathew H., Ludtmann, Marthe H., Choi, Minee L., Hughes, Craig D., Ruggeri, Francesco S., Guilliams, Tim, Buell, Alexander K., Ji-Eun Lee, Gandhi, Sonia, Lee, Steven F., Bryant, Clare E., Vendruscolo, Michele, Knowles, Tuomas P. J., Dobson, Christopher M., De Genst, Erwin, and Klenerman, David

Subjects
AMYLOID, NEURODEGENERATION, IMMUNOGLOBULINS, SINGLE molecules, FLUORESCENCE, SYNUCLEINS, OLIGOMERS
Abstract

Background: The aggregation of the protein α-synuclein (αS) underlies a range of increasingly common neurodegenerative disorders including Parkinson's disease. One widely explored therapeutic strategy for these conditions is the use of antibodies to target aggregated αS, although a detailed molecular-level mechanism of the action of such species remains elusive. Here, we characterize αS aggregation in vitro in the presence of two αS-specific single-domain antibodies (nanobodies), NbSyn2 and NbSyn87, which bind to the highly accessible C-terminal region of αS. Results: We show that both nanobodies inhibit the formation of αS fibrils. Furthermore, using single-molecule fluorescence techniques, we demonstrate that nanobody binding promotes a rapid conformational conversion from more stable oligomers to less stable oligomers of αS, leading to a dramatic reduction in oligomer-induced cellular toxicity. Conclusions: The results indicate a novel mechanism by which diseases associated with protein aggregation can be inhibited, and suggest that NbSyn2 and NbSyn87 could have significant therapeutic potential. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

17. Identifying the Science and Technology Dimensions of Emerging Public Policy Issues through Horizon Scanning

Author

Parker, Miles, primary, Acland, Andrew, additional, Armstrong, Harry J., additional, Bellingham, Jim R., additional, Bland, Jessica, additional, Bodmer, Helen C., additional, Burall, Simon, additional, Castell, Sarah, additional, Chilvers, Jason, additional, Cleevely, David D., additional, Cope, David, additional, Costanzo, Lucia, additional, Dolan, James A., additional, Doubleday, Robert, additional, Feng, Wai Yi, additional, Godfray, H. Charles J., additional, Good, David A., additional, Grant, Jonathan, additional, Green, Nick, additional, Groen, Arnoud J., additional, Guilliams, Tim T., additional, Gupta, Sunjai, additional, Hall, Amanda C., additional, Heathfield, Adam, additional, Hotopp, Ulrike, additional, Kass, Gary, additional, Leeder, Tim, additional, Lickorish, Fiona A., additional, Lueshi, Leila M., additional, Magee, Chris, additional, Mata, Tiago, additional, McBride, Tony, additional, McCarthy, Natasha, additional, Mercer, Alan, additional, Neilson, Ross, additional, Ouchikh, Jackie, additional, Oughton, Edward J., additional, Oxenham, David, additional, Pallett, Helen, additional, Palmer, James, additional, Patmore, Jeff, additional, Petts, Judith, additional, Pinkerton, Jan, additional, Ploszek, Richard, additional, Pratt, Alan, additional, Rocks, Sophie A., additional, Stansfield, Neil, additional, Surkovic, Elizabeth, additional, Tyler, Christopher P., additional, Watkinson, Andrew R., additional, Wentworth, Jonny, additional, Willis, Rebecca, additional, Wollner, Patrick K. A., additional, Worts, Kim, additional, and Sutherland, William J., additional

Published
2014
Full Text
View/download PDF

19. This title is unavailable for guests, please login to see more information.

Author

Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. CTS-541 Neuroinmunología de Enfermedades Inflamatorias, Autoinmunes y Neurodegenerativas, Roodveldt, Cintia, Labrador Garrido, Adahir, González Rey, Elena, Lachaud, Christian, Guilliams, Tim, Fernández Montesinos, Rafael, Benítez Rondan, Alicia, Robledo, Gema, Hmadcha, Abdelkrim, Delgado, Mario, Dobson, Christopher M., Pozo, D., Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. CTS-541 Neuroinmunología de Enfermedades Inflamatorias, Autoinmunes y Neurodegenerativas, Roodveldt, Cintia, Labrador Garrido, Adahir, González Rey, Elena, Lachaud, Christian, Guilliams, Tim, Fernández Montesinos, Rafael, Benítez Rondan, Alicia, Robledo, Gema, Hmadcha, Abdelkrim, Delgado, Mario, Dobson, Christopher M., and Pozo, D.

Published
2013

20. Preconditioning of Microglia by α-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation

Author

Roodveldt, Cintia, primary, Labrador-Garrido, Adahir, additional, Gonzalez-Rey, Elena, additional, Lachaud, Christian C., additional, Guilliams, Tim, additional, Fernandez-Montesinos, Rafael, additional, Benitez-Rondan, Alicia, additional, Robledo, Gema, additional, Hmadcha, Abdelkrim, additional, Delgado, Mario, additional, Dobson, Christopher M., additional, and Pozo, David, additional

Published
2013
Full Text
View/download PDF

21. Nanobodies Raised against Monomeric α-Synuclein Distinguish between Fibrils at Different Maturation Stages

Author

Guilliams, Tim, primary, El-Turk, Farah, additional, Buell, Alexander K., additional, O'Day, Elizabeth M., additional, Aprile, Francesco A., additional, Esbjörner, Elin K., additional, Vendruscolo, Michele, additional, Cremades, Nunilo, additional, Pardon, Els, additional, Wyns, Lode, additional, Welland, Mark E., additional, Steyaert, Jan, additional, Christodoulou, John, additional, Dobson, Christopher M., additional, and De Genst, Erwin, additional

Published
2013
Full Text
View/download PDF

24. Structure and Properties of a Complex of α-Synuclein and a Single-Domain Camelid Antibody

Author

De Genst, Erwin J., primary, Guilliams, Tim, additional, Wellens, Joke, additional, O'Day, Elizabeth M., additional, Waudby, Christopher A., additional, Meehan, Sarah, additional, Dumoulin, Mireille, additional, Hsu, Shang-Te Danny, additional, Cremades, Nunilo, additional, Verschueren, Koen H.G., additional, Pardon, Els, additional, Wyns, Lode, additional, Steyaert, Jan, additional, Christodoulou, John, additional, and Dobson, Christopher M., additional

Published
2010
Full Text
View/download PDF

25. The use or generation of biomedical data and existing medicines to discover and establish new treatments for patients with rare diseases - recommendations of the IRDiRC Data Mining and Repurposing Task Force.

Author

Southall, Noel T, Natarajan, Madhusudan, Lau, Lilian Pek Lian, Jonker, Anneliene Hechtelt, Deprez, Benoît, Guilliams, Tim, Hunter, Lawrence, Rademaker, Carin MA, Hivert, Virginie, Ardigò, Diego, on behalf of the IRDiRC Data Mining and Repurposing Task Force, Cavalla, David, Colvis, Christine, Hettne, Kristina, 't-Hoen, Peter-Bram, Kant, Caroline, Krischer, Jeffrey, Marin, Frédéric, Quintana, Jordi, and Rademaker, Carin MA

Subjects
RARE diseases, DATA mining, TASK forces, INDIVIDUALIZED medicine, DOSAGE forms of drugs, SYSTEM integration, CARDIAC pacing, PROGRESSION-free survival
Abstract

The number of available therapies for rare diseases remains low, as fewer than 6% of rare diseases have an approved treatment option. The International Rare Diseases Research Consortium (IRDiRC) set up the multi-stakeholder Data Mining and Repurposing (DMR) Task Force to examine the potential of applying biomedical data mining strategies to identify new opportunities to use existing pharmaceutical compounds in new ways and to accelerate the pace of drug development for rare disease patients. In reviewing past successes of data mining for drug repurposing, and planning for future biomedical research capacity, the DMR Task Force identified four strategic infrastructure investment areas to focus on in order to accelerate rare disease research productivity and drug development: (1) improving the capture and sharing of self-reported patient data, (2) better integration of existing research data, (3) increasing experimental testing capacity, and (4) sharing of rare disease research and development expertise. Additionally, the DMR Task Force also recommended a number of strategies to increase data mining and repurposing opportunities for rare diseases research as well as the development of individualized and precision medicine strategies. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

26. Additional file 2: of Nanobodies raised against monomeric É -synuclein inhibit fibril formation and destabilize toxic oligomeric species

Author

Iljina, Marija, Hong, Liu, Horrocks, Mathew, Ludtmann, Marthe, Minee Choi, Hughes, Craig, Ruggeri, Francesco, Guilliams, Tim, Buell, Alexander, Lee, Ji-Eun, Gandhi, Sonia, Lee, Steven, Bryant, Clare, Vendruscolo, Michele, Knowles, Tuomas, Dobson, Christopher, Genst, Erwin De, and Klenerman, David

Subjects
3. Good health
Abstract

Supplementary Information. (PDF 462 kb)

27. Additional file 2: of Nanobodies raised against monomeric É -synuclein inhibit fibril formation and destabilize toxic oligomeric species

Author

Iljina, Marija, Hong, Liu, Horrocks, Mathew, Ludtmann, Marthe, Minee Choi, Hughes, Craig, Ruggeri, Francesco, Guilliams, Tim, Buell, Alexander, Lee, Ji-Eun, Gandhi, Sonia, Lee, Steven, Bryant, Clare, Vendruscolo, Michele, Knowles, Tuomas, Dobson, Christopher, Genst, Erwin De, and Klenerman, David

Subjects
3. Good health
Abstract

Supplementary Information. (PDF 462 kb)

Catalog

Books, media, physical & digital resources
See catalog results