Genomes and Genes

Species

Tuomas P J Knowles

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. Łapińska U, Saar K, Yates E, Herling T, Müller T, Challa P, et al. Gradient-free determination of isoelectric points of proteins on chip. Phys Chem Chem Phys. 2017;19:23060-23067 pubmed publisher
    ..The ability to conduct measurements in free solution thus provides the basis for the rapid determination of isoelectric points of proteins under a wide variety of solution conditions and in small volumes. ..
  2. Michaels T, Sarić A, Habchi J, Chia S, Meisl G, Vendruscolo M, et al. Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation. Annu Rev Phys Chem. 2018;69:273-298 pubmed publisher
  3. Meisl G, Rajah L, Cohen S, Pfammatter M, Sarić A, Hellstrand E, et al. Scaling behaviour and rate-determining steps in filamentous self-assembly. Chem Sci. 2017;8:7087-7097 pubmed publisher
    ..The approach is general and will be applicable to any future extensions of the reaction network of filamentous self-assembly. ..
  4. Meisl G, Yang X, Dobson C, Linse S, Knowles T. Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the A?42 peptide and its variants. Chem Sci. 2017;8:4352-4362 pubmed publisher
    ..More generally, this universal reaction network connects previously separate systems, such as charge mutants of the A?42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of A?42...
  5. Herling T, García G, Michaels T, Grentz W, Dean J, Shimanovich U, et al. Force generation by the growth of amyloid aggregates. Proc Natl Acad Sci U S A. 2015;112:9524-9 pubmed publisher
    ..These findings highlight the potential of amyloid structures as active materials and shed light on the criteria for regulation and reversibility that guide molecular evolution of functional polymers. ..
  6. Ruggeri F, Sneideris T, Vendruscolo M, Knowles T. Atomic force microscopy for single molecule characterisation of protein aggregation. Arch Biochem Biophys. 2019;664:134-148 pubmed publisher
  7. Andreasen M, Meisl G, Taylor J, Michaels T, Levin A, Otzen D, et al. Physical Determinants of Amyloid Assembly in Biofilm Formation. MBio. 2019;10: pubmed publisher
    ..Our results suggest that fibril formation may be a rate-limiting step in biofilm formation, which in turn has implications on the protein self-assembly reaction as a target for potential antibiotic drugs. ..
  8. Perni M, Casford S, Aprile F, Nollen E, Knowles T, Vendruscolo M, et al. Automated Behavioral Analysis of Large C. elegans Populations Using a Wide Field-of-view Tracking Platform. J Vis Exp. 2018;: pubmed publisher
  9. Toprakcioglu Z, Challa P, Levin A, Knowles T. Observation of molecular self-assembly events in massively parallel microdroplet arrays. Lab Chip. 2018;18:3303-3309 pubmed publisher

More Information

Publications28

  1. Bortolini C, Kartanas T, Copic D, Condado Morales I, Zhang Y, Challa P, et al. Resolving protein mixtures using microfluidic diffusional sizing combined with synchrotron radiation circular dichroism. Lab Chip. 2018;19:50-58 pubmed publisher
  2. Welsh T, Shen Y, Levin A, Knowles T. Mechanobiology of Protein Droplets: Force Arises from Disorder. Cell. 2018;175:1457-1459 pubmed publisher
    ..2018). These results show that growing condensates are able to exert mechanical forces resulting in chromatin rearrangement, establishing a new role for liquid-liquid phase separation in the mechanobiology of the cell. ..
  3. Ruggeri F, Charmet J, Kartanas T, Peter Q, Chia S, Habchi J, et al. Microfluidic deposition for resolving single-molecule protein architecture and heterogeneity. Nat Commun. 2018;9:3890 pubmed publisher
  4. Ruggeri F, Marcott C, Dinarelli S, Longo G, Girasole M, Dietler G, et al. Identification of Oxidative Stress in Red Blood Cells with Nanoscale Chemical Resolution by Infrared Nanospectroscopy. Int J Mol Sci. 2018;19: pubmed publisher
    ..Using this approach, we demonstrate that we can identify localized sites of oxidative stress and membrane peroxidation on individual RBC, before the occurrence of neat morphological changes in the cellular shape. ..
  5. Arosio P, Vendruscolo M, Dobson C, Knowles T. Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol Sci. 2014;35:127-35 pubmed publisher
  6. Cohen S, Cukalevski R, Michaels T, Sarić A, Törnquist M, Vendruscolo M, et al. Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide. Nat Chem. 2018;10:523-531 pubmed publisher
  7. Knowles T, Buehler M. Nanomechanics of functional and pathological amyloid materials. Nat Nanotechnol. 2011;6:469-79 pubmed publisher
  8. Wright M, Aprile F, Arosio P, Vendruscolo M, Dobson C, Knowles T. Biophysical approaches for the study of interactions between molecular chaperones and protein aggregates. Chem Commun (Camb). 2015;51:14425-34 pubmed publisher
  9. Herling T, Levin A, Saar K, Dobson C, Knowles T. Microfluidic approaches for probing amyloid assembly and behaviour. Lab Chip. 2018;18:999-1016 pubmed publisher
    ..Finally, we highlight the salient features of microfluidic experiments that facilitate probing complex biological systems, and discuss their use in the exploration of amyloids as a class of functional material. ..
  10. Charmet J, Arosio P, Knowles T. Microfluidics for Protein Biophysics. J Mol Biol. 2018;430:565-580 pubmed publisher
  11. Perni M, Challa P, Kirkegaard J, Limbocker R, Koopman M, Hardenberg M, et al. Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery. J Neurosci Methods. 2018;306:57-67 pubmed publisher
    ..We anticipate that this approach will further extend the scope and utility of C. elegans as a model organism. ..
  12. Zhang Y, Buell A, Muller T, De Genst E, Benesch J, Dobson C, et al. Protein Aggregate-Ligand Binding Assays Based on Microfluidic Diffusional Separation. Chembiochem. 2016;17:1920-1924 pubmed publisher
    ..This method yields rapid binding information from only microlitres of sample, and is therefore a powerful technique for identifying and characterising molecular species with potential therapeutic or diagnostic application. ..
  13. Herling T, O Connell D, Bauer M, Persson J, Weininger U, Knowles T, et al. A Microfluidic Platform for Real-Time Detection and Quantification of Protein-Ligand Interactions. Biophys J. 2016;110:1957-66 pubmed publisher
    ..These findings demonstrate the potential of quantitative microfluidic techniques to characterize binding equilibria between biomolecules under native solution conditions. ..
  14. Arosio P, Cedervall T, Knowles T, Linse S. Analysis of the length distribution of amyloid fibrils by centrifugal sedimentation. Anal Biochem. 2016;504:7-13 pubmed publisher
    ..The results, which have been validated by cryogenic transmission electron microscopy (cryo-TEM) analysis, highlight the important role that fibril-fibril assembly can play in the deposition of aggregation-prone peptides. ..
  15. Saar K, Yates E, Müller T, Saunier S, Dobson C, Knowles T. Automated Ex Situ Assays of Amyloid Formation on a Microfluidic Platform. Biophys J. 2016;110:555-560 pubmed publisher
  16. Saar K, Zhang Y, Muller T, Kumar C, Devenish S, Lynn A, et al. On-chip label-free protein analysis with downstream electrodes for direct removal of electrolysis products. Lab Chip. 2017;18:162-170 pubmed publisher
  17. Guttenplan A, Young L, Matak Vinkovic D, Kaminski C, Knowles T, Itzhaki L. Nanoscale click-reactive scaffolds from peptide self-assembly. J Nanobiotechnology. 2017;15:70 pubmed publisher
  18. Michaels T, Bellaiche M, Hagan M, Knowles T. Kinetic constraints on self-assembly into closed supramolecular structures. Sci Rep. 2017;7:12295 pubmed publisher
  19. Herling T, Arosio P, Müller T, Linse S, Knowles T. A microfluidic platform for quantitative measurements of effective protein charges and single ion binding in solution. Phys Chem Chem Phys. 2015;17:12161-7 pubmed publisher
    ..Our findings highlight the difference between the dry sequence charge and the effective charge of proteins in solution, and open up a route towards rapid and quantitative charge measurements in small volumes in the condensed phase. ..