Microfluidics - chemistry and soft matter physics on small scales
Observation of spatial propagation of amyloid assembly from single nuclei, T. P. J. Knowles, D. A. White, A. R. Abate, J. J. Agresti, S. I. A. Cohen, R. A. Sperling, E. J. De Genst,C. M. Dobson and D. A. Weitz. PNAS, (2011), 108, 14746-14751
Latent analysis of unmodified biomolecules and their complexes in solution with attomole detection sensitivity, E. V. Yates, T. Müller, L. Rajah, E. J. De Genst, P. Arosio, S. Linse, M. Vendruscolo, C. M. Dobson and T. P. J. Knowles. Nature Chemistry, 7, 802-809 (2015)
Understanding the fundamental science behind pathological protein aggregation and its association with dementia
We are interested in understanding the fundamental molecular level events that drive proteins to convert from their normal soluble forms into pathological aggregates implicated in neurodgenerative disorders such as Alzheimer's and Parkinson's diseases. We undertake this work in a collaborative environment within the Cambridge Centre for Protein Misfolding Diseases. We use statistical mechanics and chemical kinetics to relate macroscopic measurements of aggregation processes under in vitro conditions to the underyling microscopic mechanisms.
Molecular mechanisms of protein aggregation from global fitting of kinetic models, G. Meisl, J. B. Kirkegaard, P. Arosio, T. C. T. Michaels, M. Vendruscolo, C. M. Dobson, S. Linse, T. P. J. Knowles, Nature Protocols 11, 252 (2016)
Proliferation of amyloid-beta42 aggregates occurs through a secondary nucleation mechanism, S. I. A. Cohen, S. Linse, L. M. Luheshi, E. Hellstrand, D. A. White, L. Rajah, D. E. Otzen, M. Vendruscolo, C. M. Dobson, T. P.J.Knowles, Proceedings of the National Academy of Sciences, 11, 9758 (2013)
Novel biomaterials from proteins
Protein molecules have the ability to form a rich variety of natural and artificial structures and materials. We are exploring the use of natural proteins as the basis of a range of artificial structures, including biofilms, microgels and capsules.
Nanomechanics of functional and pathological amyloid materials, T. P. J. Knowles and M. J. Buehler, Nature Nanotechnology, 6, 469-479 (2011)
Role of intermolecular forces in defining material properties of protein nanofibrils, T. P. Knowles, A. W. Fitzpatrick, S. Meehan, H. R. Mott, M. Vendruscolo, C. M. Dobson and M. E. Welland, Science, 318, 1900-1903 (2007)
Fabrication of fibrillosomes from droplets stablized by protein nanofibrils at all-aqueous interfaces, Y. Song, U. Shimanovich, T. C. T. Michaels, Q. Ma, J. Li, T. P. J. Knowles, H. C. Shum, Nature Communications 7 12934 (2016)