Professor Tuomas Knowles

University Position


We work on the physico-chemical properties and behaviour of biological molecules and soft materials. The research in the group is highly interdisciplinary. Members of the group have a wide range of backgrounds. We used methods from biochemistry, chemistry, chemical engineering and physics, and work in close collaboration with other groups in Cambridge and overseas. We apply new physical methods to understand the misfolding and aggregation of proteins molecules into amyloid fibrils of the type encountered in neurodegenerative disorders. The techniques used in our laboratory include biosensors, optical lithography, microfluidic devices and scanning probe microscopy and spectroscopy. We also have an interest in applying theoretical concepts from statistical mechanics and chemical kinetics to protein systems.

Key Publications

Structure-specific amyloid precipitation in biofluids.

Journal: Nat Chem
E-pub date: 1 Sep 2022
Authors: M Rodrigues, P Bhattacharjee, A Brinkmalm, DT Do, CM Pearson, S De, A Ponjavic, JA Varela, K Kulenkampff, I Baudrexel, D Emin, FS Ruggeri, JE Lee, AR Carr, TPJ Knowles, H Zetterberg, TN Snaddon, S Gandhi, SF Lee, D Klenerman

The Pathological G51D Mutation in Alpha-Synuclein Oligomers Confers Distinct Structural Attributes and Cellular Toxicity.

Journal: Molecules
E-pub date: 15 Feb 2022
Authors: CK Xu, M Castellana-Cruz, SW Chen, Z Du, G Meisl, A Levin, B Mannini, LS Itzhaki, TPJ Knowles, CM Dobson, N Cremades, JR Kumita

Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1

Journal: Cell
E-pub date: 19 Apr 2018
Authors: PH St George-Hyslop, S Qamar, G Wang, SJ Randle, FS Ruggeri, J Varela, CF Kaminski, GS Kaminski, M Vendruscolo, TPJ Knowles, D Klenerman, CE Holt, Q Lin, W meadows

Direct observation of the interconversion of normal and toxic forms of α-synuclein.

Journal: Cell
E-pub date: 25 May 2012
Authors: N Cremades, SIA Cohen, E Deas, AY Abramov, AY Chen, A Orte, M Sandal, RW Clarke, P Dunne, FA Aprile, CW Bertoncini, NW Wood, TPJ Knowles, CM Dobson, D Klenerman


Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease

Journal: Nature Communications
E-pub date: 20 Sep 2022
Authors: D Emin, YP Zhang, E Lobanova, A Miller, X Li, Z Xia, H Dakin, DI Sideris, JYL Lam, RT Ranasinghe, A Kouli, Y Zhao, S De, TPJ Knowles, M Vendruscolo, FS Ruggeri, FI Aigbirhio, CH Williams-Gray, D Klenerman

Rate‐limiting processes of tau aggregate accumulation in Alzheimer’s disease

Journal: Alzheimer's & Dementia
E-pub date: 1 Dec 2021
Authors: G Meisl, Y Zuo, K Allinson, T Rittman, SL DeVos, JS Sanchez, CK Xu, KE Duff, KA Johnson, JB Rowe, BT Hyman, T Knowles, D Klenerman

In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease.

Journal: Sci Adv
E-pub date: 29 Oct 2021
Authors: G Meisl, E Hidari, K Allinson, T Rittman, SL DeVos, JS Sanchez, CK Xu, KE Duff, KA Johnson, JB Rowe, BT Hyman, TPJ Knowles, D Klenerman

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers.

Journal: Front Neurosci
E-pub date: 1 Aug 2021
Authors: R Limbocker, R Staats, S Chia, FS Ruggeri, B Mannini, CK Xu, M Perni, R Cascella, A Bigi, LR Sasser, NR Block, AK Wright, RP Kreiser, ET Custy, G Meisl, S Errico, J Habchi, P Flagmeier, T Kartanas, JE Hollows, LT Nguyen, K LeForte, D Barbut, JR Kumita, C Cecchi, M Zasloff, TPJ Knowles, CM Dobson, F Chiti, M Vendruscolo

A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers.

Journal: Commun Biol
E-pub date: 4 Jan 2021
Authors: R Cataldi, S Chia, K Pisani, FS Ruggeri, CK Xu, T Šneideris, M Perni, S Sarwat, P Joshi, JR Kumita, S Linse, J Habchi, TPJ Knowles, B Mannini, CM Dobson, M Vendruscolo

Rapid Structural, Kinetic, and Immunochemical Analysis of Alpha-Synuclein Oligomers in Solution.

Journal: Nano Lett
E-pub date: 11 Nov 2020
Authors: WE Arter, CK Xu, M Castellana-Cruz, TW Herling, G Krainer, KL Saar, JR Kumita, CM Dobson, TPJ Knowles

Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism.

Journal: Commun Biol
E-pub date: 13 Aug 2020
Authors: R Limbocker, B Mannini, FS Ruggeri, R Cascella, CK Xu, M Perni, S Chia, SW Chen, J Habchi, A Bigi, RP Kreiser, AK Wright, JA Albright, T Kartanas, JR Kumita, N Cremades, M Zasloff, C Cecchi, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson

The Influence of Pathogenic Mutations in α-Synuclein on Biophysical and Structural Characteristics of Amyloid Fibrils.

Journal: ACS Nano
E-pub date: 26 May 2020
Authors: FS Ruggeri, P Flagmeier, JR Kumita, G Meisl, DY Chirgadze, MN Bongiovanni, TPJ Knowles, CM Dobson

Fabrication and Characterization of Reconstituted Silk Microgels for the Storage and Release of Small Molecules.

Journal: Macromol Rapid Commun
E-pub date: 1 Apr 2019
Authors: X Liu, Z Toprakcioglu, AJ Dear, A Levin, FS Ruggeri, CG Taylor, M Hu, JR Kumita, M Andreasen, CM Dobson, U Shimanovich, TPJ Knowles

Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes.

Journal: Nat Commun
E-pub date: 15 Jan 2019
Authors: 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

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

Journal: ACS Chem Biol
E-pub date: 17 Aug 2018
Authors: M Perni, P Flagmeier, R Limbocker, R Cascella, FA Aprile, C Galvagnion, GT Heller, G Meisl, SW Chen, JR Kumita, PK Challa, JB Kirkegaard, SIA Cohen, B Mannini, D Barbut, EAA Nollen, C Cecchi, N Cremades, TPJ Knowles, F Chiti, M Zasloff, M Vendruscolo, CM Dobson

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes.

Journal: Nat Chem
E-pub date: 1 Jun 2018
Authors: J Habchi, S Chia, C Galvagnion, TCT Michaels, MMJ Bellaiche, FS Ruggeri, M Sanguanini, I Idini, JR Kumita, E Sparr, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo

Inhibition of α-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α-Synuclein Species.

Journal: Biochemistry
E-pub date: 7 Mar 2017
Authors: FA Aprile, P Arosio, G Fusco, SW Chen, JR Kumita, A Dhulesia, P Tortora, TPJ Knowles, M Vendruscolo, CM Dobson, N Cremades

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease.

Journal: Proc Natl Acad Sci U S A
E-pub date: 10 Jan 2017
Authors: J Habchi, S Chia, R Limbocker, B Mannini, M Ahn, M Perni, O Hansson, P Arosio, JR Kumita, PK Challa, SIA Cohen, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo

Population of nonnative states of lysozyme variants drives amyloid fibril formation.

Journal: J Am Chem Soc
E-pub date: 25 May 2011
Authors: AK Buell, A Dhulesia, MF Mossuto, N Cremades, JR Kumita, M Dumoulin, ME Welland, TPJ Knowles, X Salvatella, CM Dobson

Methods and models in neurodegenerative and systemic protein aggregation diseases.

Journal: Front Biosci (Landmark Ed)
E-pub date: 1 Jan 2010
Authors: A-C Brorsson, JR Kumita, I MacLeod, B Bolognesi, E Speretta, LM Luheshi, TPJ Knowles, CM Dobson, DC Crowther