研究领域

Physical/Biological

We study the physical and chemical aspects of the behaviour of biopolymers and other soft systems. Much of our work has been focused on the physical aspects underlying the self-assembly of protein molecules. Self-organisation is the driving force generating complex matter in nature, and the process by which the machinery providing functionality in living systems is assembled. The goal of our research is to understand the physical and chemical factors which control the structures and dynamics of biomolecular assemblies, and the connections between the nanoscale characteristics of the component molecules and the physical properties of large-scale assemblies and their behaviour on a mesoscopic to macroscopic scale. The techniques used in our laboratory include biosensors, optical lithography, microfluidic devices and scanning probe microscopy and spectroscopy. We work both with natural and synthetic polymers and our interests range from fundamental chemical physics to technological applications in material science and molecular medicine.

近期论文

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Trodusquemine enhances A beta(42) aggregation but suppresses its toxicity by displacing oligomers from cell membranes R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson – Nature communications (2019) 10, 225 (DOI: 10.1038/s41467-018-07699-5) Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer's disease progression.S De, DR Whiten, FS Ruggeri, C Hughes, M Rodrigues, DI Sideris, CG Taylor, FA Aprile, S Muyldermans, TPJ Knowles, M Vendruscolo, C Bryant, K Blennow, I Skoog, S Kern, H Zetterberg, D Klenerman – Acta Neuropathologica Communications (2019) 7, 120 (DOI: 10.1186/s40478-019-0777-4) Scalable integration of nano-, and microfluidics with hybrid two-photon lithography O Vanderpoorten, Q Peter, PK Challa, UF Keyser, J Baumberg, CF Kaminski, TPJ Knowles – Microsystems and Nanoengineering (2019) 5, 40 (DOI: 10.1038/s41378-019-0080-3) Nucleation and Growth of Amino-acid and Peptide Supramolecular Polymers through Liquid-liquid Phase Separation X Yan, C Yuan, A Levin, W Chen, R Xing, Q Zou, TW Herling, PK Challa, TPJ Knowles – Angewandte Chemie (International ed. in English) (2019) (DOI: 10.1002/anie.201911782) Modulating the Mechanical Performance of Macroscale Fibers through Shear-Induced Alignment and Assembly of Protein Nanofibrils.A Kamada, A Levin, Z Toprakcioglu, Y Shen, V Lutz-Bueno, KN Baumann, P Mohammadi, MB Linder, R Mezzenga, TPJ Knowles – Small (2019) e1904190 (DOI: 10.1002/smll.201904190) RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether.Y-C Liao, MS Fernandopulle, G Wang, H Choi, L Hao, CM Drerup, R Patel, S Qamar, J Nixon-Abell, Y Shen, W Meadows, M Vendruscolo, TPJ Knowles, M Nelson, MA Czekalska, G Musteikyte, MA Gachechiladze, CA Stephens, HA Pasolli, LR Forrest, P St George-Hyslop, J Lippincott-Schwartz, ME Ward – Cell (2019) 179, 147 (DOI: 10.1016/j.cell.2019.08.050) Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy FS Ruggeri, T Šneideris, S Chia, M Vendruscolo, TPJ Knowles – JoVE (2019) (DOI: 10.3791/60108) Enhancement of the Anti-Aggregation Activity of a Molecular Chaperone Using a Rationally Designed Post-Translational Modification PR Lindstedt, FA Aprile, MJ Matos, M Perni, JB Bertoldo, B Bernardim, Q Peter, G Jiménez-Osés, TPJ Knowles, CM Dobson, F Corzana, M Vendruscolo, GJL Bernardes – ACS Cent Sci (2019) 5, 1417 (DOI: 10.1021/acscentsci.9b00467) Small molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease G Heller, F Aprile, T Michaels, R Limbocker, M Perni, FS Ruggeri, B Mannini, T Löhr, M Bonomi, A De Simone, I Felli, R Pierattelli, T Knowles, C Dobson, M Vendruscolo (2019) (DOI: 10.1101/729392) Analysis of alpha B-crystallin polydispersity in solution through native microfluidic electrophoresis MA Wright, FS Ruggeri, KL Saar, PK Challa, JLP Benesch, TPJ Knowles – Analyst (2019) 144, 4413 (DOI: 10.1039/c9an00382g) Rapid two-dimensional characterisation of proteins insolution KL Saar, Q Peter, T Müller, PK Challa, TW Herling, TPJ Knowles – Microsyst Nanoeng (2019) 5, 33 (DOI: 10.1038/s41378-019-0072-3) Universality of filamentous aggregation phenomena TCT Michaels, AJ Dear, TPJ Knowles – Physical Review E (2019) 99, 062415 (DOI: 10.1103/physreve.99.062415) Analysis of αB-crystallin polydispersity in solution through native microfluidic electrophoresis.MA Wright, FS Ruggeri, KL Saar, PK Challa, JLP Benesch, TPJ Knowles – The Analyst (2019) 144, 4413 (DOI: 10.1039/c9an00382g) Programmable On-Chip Artificial Cell Producing Post-Translationally Modified Ubiquitinated Protein S Zilberzwige-Tal, A Levin, Z Toprakcioglu, TPJ Knowles, E Gazit, J Elbaz – Small (Weinheim an der Bergstrasse, Germany) (2019) 15, 1901780 (DOI: 10.1002/smll.201901780) Different soluble aggregates of A beta 42 can give rise to cellular toxicity through different mechanisms S De, DC Wirthensohn, P Flagmeier, C Hughes, FA Aprile, FS Ruggeri, DR Whiten, D Emin, Z Xia, JA Varela, P Sormanni, F Kundel, TPJ Knowles, CM Dobson, C Bryant, M Vendruscolo, D Klenerman – Nat Commun (2019) 10, 1541 (DOI: 10.1038/s41467-019-09477-3) Secondary nucleation and elongation occur at different sites on Alzheimer's amyloid-beta aggregates T Scheidt, U Łapińska, JR Kumita, DR Whiten, D Klenerman, MR Wilson, SIA Cohen, S Linse, M Vendruscolo, CM Dobson, TPJ Knowles, P Arosio – Science advances (2019) 5, eaau3112 (DOI: 10.1126/sciadv.aau3112) The Amyloid Phenomenon and Its Significance in Biology and Medicine.CM Dobson, TPJ Knowles, M Vendruscolo – Cold Spring Harbor perspectives in biology (2019) a033878 (DOI: 10.1101/cshperspect.a033878) Direct observation of prion protein oligomer formation reveals an aggregation mechanism with multiple conformationally distinct species JC Sang, J-E Lee, AJ Dear, S De, G Meisl, AM Thackray, R Bujdoso, TPJ Knowles, D Klenerman – Chemical science (2019) 10, 4588 (DOI: 10.1039/c8sc05627g) Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine-Selective Protein Modification and Charge Modulation.MJ Matos, CD Navo, T Hakala, X Ferhati, A Guerreiro, D Hartmann, B Bernardim, KL Saar, I Compañón, F Corzana, TPJ Knowles, G Jiménez-Osés, GJL Bernardes – Angewandte Chemie International Edition (2019) 58, 6640 (DOI: 10.1002/anie.201901405) Fabrication and Characterization of Reconstituted Silk Microgels for the Storage and Release of Small Molecules.X Liu, Z Toprakcioglu, AJ Dear, A Levin, FS Ruggeri, CG Taylor, M Hu, JR Kumita, M Andreasen, CM Dobson, U Shimanovich, TPJ Knowles – Macromolecular Rapid Communications (2019) 40, e1800898 (DOI: 10.1002/marc.201800898)