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32 results on '"Elliott, Thomas S."'

4. Design and synthesis of chemical probes for the plekstrin homology domain

Author

Elliott, Thomas S. and Conway, Stuart

Subjects
572, Inositol, Inositol phosphates, Phosphatidylinositol, Protein kinase B, QP752.P52E6, Phosphoinositides--Derivatives--Synthesis, Inositol, Inositol phosphates, Protein kinases, Molecular probes
Abstract

The phosphatidylinositol polyphosphates play a fundamental role in intracellular signalling. Of particular importance is phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P₃], which acts by recruiting effector proteins to the cell membrane. PtdIns(3,4,5)P₃ interacts with its protein targets through selective binding domains that include the pleckstrin homology (PH) domain. The PH-domain-containing kinase, protein kinase B (PKB/Akt), which interacts with PtdIns(3,4,5)P₃, is upregulated in ~15 human malignancies. Significantly, inhibition of the PtdIns(3,4,5)P₃-PKB interaction has proved viable as a point of therapeutic intervention. There is currently a lack of small molecule probes that selectively interact with a given PH domain. Consequently, it is impossible to dissect the cellular function of PH-domain-containing proteins at a molecular level. To address this problem, we have designed and synthesised a number of derivatives of the PtdIns(3,4,5)P₃ inositol head-group – Ins(1,3,4,5)P₄. Replacement of the 5-position phosphate with a range of phosphate bioisosteres afforded compounds that displayed no binding affinity for the PH-domain of general receptor for phosphoinositides 1 (GRP1). However, it was shown that the 5-position sulfamate analogue displayed selectivity for the PH-domain of PKB. The methylphosphate biosiostere at the 1-position displayed binding for both the GRP1 PH-domain as well as the PKB PH-domain. These results demonstrate that subtle modification of the Ins(1,3,4,5)P₄ structure allows the synthesis of compounds that interact selectively with a given PH domain. We will now use these results for the synthesis of a second generation of compounds with improved PH-domain affinity and selectivity.

Published
2010

5. Total synthesis of Escherichia coli with a recoded genome

Author

Fredens, Julius, Wang, Kaihang, de la Torre, Daniel, Funke, Louise F. H., Robertson, Wesley E., Christova, Yonka, Chia, Tiongsun, Schmied, Wolfgang H., Dunkelmann, Daniel L., Beránek, Václav, Uttamapinant, Chayasith, Llamazares, Andres Gonzalez, Elliott, Thomas S., and Chin, Jason W.

Published
2019
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7. Cell-of-origin-specific proteomics of extracellular vesicles

Author

Kehrloesser, Sebastian, Cast, Oliver, Elliott, Thomas S, Ernst, Russell J, Machel, Anne C, Chen, Jia-Xuan, Chin, Jason W, Miller, Martin L, Cast, Oliver [0000-0002-5880-7726], Miller, Martin L [0000-0003-3161-8690], and Apollo - University of Cambridge Repository

Subjects
proteomics, extracellular vesicles, cell-specific labeling, intercellular signaling
Abstract

The ability to assign cellular origin to low-abundance secreted factors in extracellular vesicles (EVs) would greatly facilitate the analysis of paracrine-mediated signaling. Here, we report a method, named selective isolation of extracellular vesicles (SIEVE), which uses cell type-specific proteome labeling via stochastic orthogonal recoding of translation (SORT) to install bioorthogonal reactive groups into the proteins derived from the cells targeted for labeling. We establish the native purification of intact EVs from a target cell, via a bioorthogonal tetrazine ligation, leading to copurification of the largely unlabeled EV proteome from the same cell. SIEVE enables capture of EV proteins at levels comparable with those obtained by antibody-based methods, which capture all EVs regardless of cellular origin, and at levels 20× higher than direct capture of SORT-labeled proteins. Using proteomic analysis, we analyze nonlabeled cargo proteins of EVs and show that the enhanced sensitivity of SIEVE allows for unbiased and comprehensive analysis of EV proteins from subpopulations of cells as well as for cell-specific EV proteomics in complex coculture systems. SIEVE can be applied with high efficiency in a diverse range of existing model systems for cell-cell communication and has direct applications for cell-of-origin EV analysis and for protein biomarker discovery.

Published
2023

14. Sense codon reassignment enables viral resistance and encoded polymer synthesis

Author

Robertson, Wesley E., primary, Funke, Louise F. H., additional, de la Torre, Daniel, additional, Fredens, Julius, additional, Elliott, Thomas S., additional, Spinck, Martin, additional, Christova, Yonka, additional, Cervettini, Daniele, additional, Böge, Franz L., additional, Liu, Kim C., additional, Buse, Salvador, additional, Maslen, Sarah, additional, Salmond, George P. C., additional, and Chin, Jason W., additional

Published
2021
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19. Labeling and identifying cell-specific proteomes in the mouse brain

Author

Krogager, Toke P, primary, Ernst, Russell J, additional, Elliott, Thomas S, additional, Calo, Laura, additional, Beránek, Václav, additional, Ciabatti, Ernesto, additional, Spillantini, Maria Grazia, additional, Tripodi, Marco, additional, Hastings, Michael H, additional, and Chin, Jason W, additional

Published
2017
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22. Genetic code expansion in the mouse brain

Author

Ernst, Russell J, primary, Krogager, Toke P, additional, Maywood, Elizabeth S, additional, Zanchi, Roberto, additional, Beránek, Václav, additional, Elliott, Thomas S, additional, Barry, Nicholas P, additional, Hastings, Michael H, additional, and Chin, Jason W, additional

Published
2016
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23. Labeling and identifying cell-specific proteomes in the mouse brain.

Author

Krogager, Toke P, Ernst, Russell J, Elliott, Thomas S, Calo, Laura, Beránek, Václav, Ciabatti, Ernesto, Spillantini, Maria Grazia, Tripodi, Marco, Hastings, Michael H, and Chin, Jason W

Abstract

We develop an approach to tag proteomes synthesized by specific cell types in dissociated cortex, brain slices, and the brains of live mice. By viral-mediated expression of an orthogonal pyrrolysyl-tRNA synthetase-tRNAXXX pair in a cell type of interest and providing a non-canonical amino acid with a chemical handle, we selectively label neuronal or glial proteomes. The method enables the identification of proteins from spatially and genetically defined regions of the brain. [ABSTRACT FROM AUTHOR]

Published
2018
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24. Total synthesis of Escherichia coliwith a recoded genome

Author

Fredens, Julius, Wang, Kaihang, de la Torre, Daniel, Funke, Louise F. H., Robertson, Wesley E., Christova, Yonka, Chia, Tiongsun, Schmied, Wolfgang H., Dunkelmann, Daniel L., Beránek, Václav, Uttamapinant, Chayasith, Llamazares, Andres Gonzalez, Elliott, Thomas S., and Chin, Jason W.

Abstract

Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon—out of up to 6 synonyms—to encode each amino acid. Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coliwith a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme—with simple corrections at just seven positions—to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA.

Published
2019
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25. Proteome labeling and protein identification in specific tissues and at specific developmental stages in an animal

Author

Elliott, Thomas S, primary, Townsley, Fiona M, additional, Bianco, Ambra, additional, Ernst, Russell J, additional, Sachdeva, Amit, additional, Elsässer, Simon J, additional, Davis, Lloyd, additional, Lang, Kathrin, additional, Pisa, Rudolf, additional, Greiss, Sebastian, additional, Lilley, Kathryn S, additional, and Chin, Jason W, additional

Published
2014
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28. Selective decontamination of the digestive tract reduces Gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation

Author

Bion, Julian F., primary, Badger, Ian, additional, Crosby, Heather A., additional, Hutchings, Paul, additional, Kong, Kim-Leung, additional, Baker, Jim, additional, Hutton, Peter, additional, McMaster, Paul, additional, Buckels, John A., additional, and Elliott, Thomas S. J., additional

Published
1994
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29. Labeling and identifying cell-specific proteomes in the mouse brain

Author

Krogager, Toke P, Ernst, Russell J, Elliott, Thomas S, Calo, Laura, Beránek, Václav, Ciabatti, Ernesto, Spillantini, Maria Grazia, Tripodi, Marco, Hastings, Michael H, and Chin, Jason W

Subjects
Amino Acyl-tRNA Synthetases, Neurons, Mice, Proteome, RNA, Transfer, Animals, Brain, Amino Acids, Neuroglia, Gene Expression Regulation, Enzymologic, 3. Good health
Abstract

We develop an approach to tag proteomes synthesized by specific cell types in dissociated cortex, brain slices, and the brains of live mice. By viral-mediated expression of an orthogonal pyrrolysyl-tRNA synthetase-tRNAXXX pair in a cell type of interest and providing a non-canonical amino acid with a chemical handle, we selectively label neuronal or glial proteomes. The method enables the identification of proteins from spatially and genetically defined regions of the brain., Michael J Fox Foundation (MJFF) (unknown), Parkinson's UK (None), Cure Parkinson's Trust (unknown)

31. Clinical evaluation of a chlorhexidine intravascular catheter gel dressing on short-term central venous catheters.

Author

Karpanen TJ, Casey AL, Whitehouse T, Nightingale P, Das I, and Elliott TS

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Bandages adverse effects, Chlorhexidine administration & dosage, Chlorhexidine adverse effects, Critical Care, Endovascular Procedures adverse effects, Female, Humans, Male, Middle Aged, Prospective Studies, Skin microbiology, Sutures microbiology, Young Adult, Catheter-Related Infections prevention & control, Catheterization, Central Venous adverse effects, Central Venous Catheters microbiology, Chlorhexidine analogs & derivatives
Abstract

Background: A major source of microbial colonization of short-term central venous catheters (CVC) is the patients' endogenous skin microorganisms located at the CVC insertion site. The aim of this study was to determine if a transparent film dressing incorporating a 2% (weight/weight) chlorhexidine gluconate (CHG) gel decreases CVC and insertion site microbial colonization compared with a nonantimicrobial dressing in adult patients in critical care., Methods: On CVC removal, samples for microbiological investigation were taken from both the skin surrounding the CVC insertion site and also from sutures securing the CVC. The sutures and intradermal and tip sections of the CVC were also collected for microbiological investigation. Microorganisms recovered from the samples were subsequently tested for susceptibility to CHG., Results: There was a significant reduction in the number of microorganisms recovered from the CVC insertion site, suture site, sutures, and catheter surface in the CHG dressing group (n = 136) compared with the nonantimicrobial dressing group (n = 137). There was no significant difference in susceptibility to CHG between the microorganisms isolated from the CHG and standard dressing study patients., Conclusion: A film dressing incorporating a CHG gel pad significantly reduced the number of microorganisms at the CVC insertion and suture sites with concomitant reduced catheter colonization., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Published
2016
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32. Role of troponin I in active infective endocarditis.

Author

Watkin RW, Lang S, Smith JM, Elliott TS, and Littler WA

Subjects
Acute Disease, Adult, Aged, Aortic Valve microbiology, C-Reactive Protein metabolism, Eikenella corrodens, Endocarditis, Bacterial microbiology, Enterobacteriaceae Infections microbiology, Female, Gram-Negative Bacterial Infections metabolism, Gram-Negative Bacterial Infections microbiology, Gram-Negative Bacterial Infections physiopathology, Heart Valve Diseases metabolism, Heart Valve Diseases microbiology, Heart Valve Diseases physiopathology, Humans, Male, Middle Aged, Mitral Valve microbiology, Staphylococcal Infections microbiology, Streptococcal Infections microbiology, Troponin I metabolism, Endocarditis, Bacterial metabolism, Endocarditis, Bacterial physiopathology, Enterobacteriaceae Infections metabolism, Enterobacteriaceae Infections physiopathology, Staphylococcal Infections metabolism, Staphylococcal Infections physiopathology, Streptococcal Infections metabolism, Streptococcal Infections physiopathology, Troponin I physiology
Abstract

Infective endocarditis (IE) remains a disease associated with high morbidity and mortality rates. In this pilot study, the role of troponin I in IE was assessed. Myocardial involvement distal to the site of infection in IE has been previously described. Elevated troponin was demonstrated in 11 of 15 patients diagnosed with the condition. Patients diagnosed with staphylococcal endocarditis were more likely to have elevated troponin (3 of 3 patients). Patients with elevated troponin I were not more likely to need valve replacement. Troponin I levels did not predict perivalvular extension. It is hypothesized that elevated troponin I is a reflection of myocardial involvement.

Published
2004
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