Professor Sergi Garcia-Manyes
Telephone: +44 020 7848 7106
Research Group: Biological Physics & Soft Matter Group
Prof. Sergi Garcia-Maynes' profile at the Thomas Young Centre
Prof. Sergi Garcia-Manyes graduated in Chemistry (BSc) from the University of Barcelona in 2000 with Honors. He got his MSc in Analytical Chemistry in 2001 and obtained his PhD in Physical Chemistry from the same University in 2005 under the supervision of Prof. Fausto Sanz. His PhD work focused on the study of the nanomechanical properties of well-defined surfaces using SPM techniques, mainly AFM. These studies gained insight into the basic elastic and plastic deformation properties of a wide variety of substrates, spanning from ionic crystals to HOPG and lipid bilayers, at the nanoscale. During his PhD studies, he undertook short research visits to the Materials Science Division of the Lawrence Berkeley National Lab (California) in the group of Prof. Miquel Salmeron and to the Biology Department of Columbia University (New York), in the group of Prof. Julio Fernandez.
Shortly after completing his PhD, Sergi joined the group of Prof. Julio Fernandez at Columbia University, firstly as a postdoctoral researcher and then as a research associate. From 2005 until 2012 he used the newly developed single molecule force-clamp technique to study the conformational dynamics of single proteins during their individual folding pathways and to elucidate the effect of a mechanical force on the outcome of a chemical reaction, at the single bond level. His research has been published in several papers in the leading journals of the field.
In 2012 Sergi established his laboratory at King’s College London, where he is a tenured Reader in Biophysics in the Department of Physics and a group leader in Structural Biology in the Randall Division of Cell and Molecular Biophysics. His multidisciplinary research group is composed of a mixture of talented PhD students and postdoctoral researchers, the aim of which is to understand how mechanical force affects the mechanical stability of cellular membranes and also to elucidate how individual proteins equilibrate under the effect of a calibrated mechanical force. Sergi was recipient of the 2012 award of the Spanish Biophysical Society. He is currently funded by the European Union through three grants from the Marie Curie Action, by the BBSRC research council, by the Royal Society, by the British Heart Foundation and by Fight for Sight. He is recipient of the prestigious EPSRC Early Career Fellowship.
The main focus of Sergi's research is to understand the molecular mechanisms that confer mechanical stability to well-defined systems, which is a major challenge in modern physics, chemistry and biology.
For example, while cell mechanics are known to play a decisive role in determining cell shape and also in endo- and exocytosis, the chemical origin of the membrane mechanical resistance remains largely unknown. Using force-spectroscopy AFM, the team can decipher the molecular determinants that provide lipid bilayers with unexpectedly high mechanical stabilities.
Most importantly, Sergi's team investigate the molecular mechanisms by which proteins equilibrate under the effect of a constant stretching force. We use the newly developed single molecule force-clamp spectroscopy technique to elucidate, with exquisite sub-Ǻngström sensitivity, the dynamics of proteins as they unfold, collapse and refold in response to a mechanical force. Sergi is most interested in examining the conformational dynamics of a single refolding protein during its individual folding trajectory from highly extended states.
Finally, they use a force-clamp assay to examine, at the single bond level, how force affects the chemical mechanisms of disulfide bond reduction in proteins exposed to mechanical forces. Within a multidisciplinary approach, they conduct a series of innovative experiments to directly probe the effect of force on the function of an individual folding polypeptide and also the mechanisms by which mechanical forces modulate chemical reactions. The force spectroscopy data is providing a new view that will help guide the development of theories on the dynamics of folding and ab-initio studies of a chemical reaction placed under a stretching force, of common occurrence in nature.
Fraxedas, J.; Garcia-Manyes, S.; Gorostiza, P.; Sanz, F., «Nanoindentation: towards the sensing of atomic interactions», Proc. Natl. Acad. Sci. USA (2002), 99, 5228-5232.
Garcia-Manyes, S.; Oncins, G.; Sanz, F., «Effect of ion-binding and chemical phospholipid structure on the nanomechanics of lipid bilayers studied by Force Spectroscopy», Biophysical Journal (2005), 89 (3), 1812-1826.
Garcia-Manyes, S.; Oncins, G.; Sanz, F., «Effect of temperature on the nanomechanics of lipid bilayers studied by Force Spectroscopy», Biophysical Journal (2005), 89 (6), 4261-4274.
Garcia-Manyes, S.; Brujic, J.; Badilla, C. L.; Fernandez, J. M.; «Force-clamp spectroscopy of single protein monomers reveal the individual unfolding and folding pathways of I27 and ubiquitin», Biophysical Journal (2007), 93, 2436-2446.
Garcia-Manyes, S*; Liang, J.; Szoszkiewicz, R.; Kuo, T.; Fernandez, J.M.; «Force-activated reactivity switch in a bimolecular chemical reaction», Nature Chemistry, (2009), 3, 236-242. Featured in the News and Views of the same issue, Frank, I and Hofbauer, F. «Breaking bonds at a stretch», Nature Chemistry (2009) 3, 180-181.
Garcia-Manyes, S.*; Dougan, L.; Badilla, C. L.; Brujic, J; Fernandez, J.M.; «Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin», Proc. Natl. Acad. Sci. USA, (2009), 106 (26),10534-10539.
Garcia-Manyes, S*.; Dougan, L.; Fernandez, J.M.; «Osmolyte induced separation of the mechanical folding phases of ubiquitin», Proc. Natl. Acad. Sci. USA, (2009), 106 (26)10540-10545.
Fernandez, J.M., Garcia-Manyes, S.; Dougan, L. «Force-clamp spectroscopy of single proteins», in Single Molecule Spectroscopy in Chemistry, Physics and Biology: Nobel Symposium, Edited by Astrid Gräslund, Rudolf Rigler and Jerker Widengren (Springer Series in Chemical Physics), 2009.
Kuo, TL.; Garcia-Manyes, S.; Li, J.; Barel, I.; Lu, H.; Berne, B.J.; Urbakh, M.; Klafter, J.; Fernández, J.M., «Probing disorder in Arrhenius with single molecule force spectroscopy», Proc. Natl. Acad. Sci. USA, (2010), 107 (25) 11336-11340.
Garcia-Manyes, S*.; Redondo-Morata, L.; Oncins, G.; Sanz, F.; «Nanomechanics of lipid bilayers: heads or tails?», Journal of the American Chemical Society (2010), 132 (7) 12874-12886.
Garcia-Manyes, S*. «Caught in the act», Nature Chemistry, (2010), 2, 905-906.
Garcia-Manyes, S*; Kuo, TL.; Fernández, J.M., «Contrasting the individual reactive pathways in protein unfolding and disulfide bond reduction observed within a single protein», Journal of the American Chemical Society (2011), 133 (9), 3104-3113.
Perez-Jimenez, R.; Inglés-Prieto, A.; Zhao, Z.M.; Sanchez-Romero, I.; Alegre- Cebollada J.; Kosuri, P.; Garcia-Manyes, S.; Holmgren, A.; Kappock, T.J.; Tanokura, M.; Sanchez-Ruiz J.M.; Gaucher, E.A.; Fernandez, J.M., «Paleoenzymology at the single-molecule level: probing the chemistry of resurrected enzymes», Nature Structural & Molecular Biology (2011), 18, 592-596.
Popa, I; Fernandez, J.M.; Garcia-Manyes, S*. «Direct quantification of the attempt frequency determining the mechanical unfolding of ubiquitin protein», Journal of Biological Chemistry, (2011), 286 (36), 31072-31079.
Applications are invited for research in the Experimental Biophysics & Nanotechnology group.
To apply for the Physics MPhil/PhD please fill in an application form. Further details and guidelines can be found here.
All relevant information regarding eligibility, including academic and English language requirements, is available from the online prospectus.
Funding your PhD
We have several funded opportunities available. All eligible applications will be automatically considered for these award. There are a number of funding schemes available associated with different application deadlines and eligibility requirements. Please visit our 'Funding your PhD' webpage for further details.
For further details contact Dr Sergi Garcia-Manyes and or the Postgraduate Tutor Dr Cedric Weber.
Conformational dynamics in the folding trajectory of a single protein under force
The PhD Project aims at studying the conformational dynamics of single protein molecules under the effect of a calibrated constant pulling force. We will track the individual folding pathways experienced by a single protein during its journey to the native, folded state from highly extended states. Using a force-quench approach, we will dissect the individual folding trajectories in order to understand the physical mechanisms that govern each state involved in the folding trajectory of a variety of proteins. Contrary to previous belief, our force-clamp experiments demonstrate that the acquisition of the protein’s native conformation occurs after dynamic maturation of an ensemble of collapsed states. Remarkably, the existence of such newly discovered ensemble of collapsed states that hold the key to explaining how an extended polypeptide folds while regaining its mechanical stability is likely to have profound implications on the onset of conformational diseases, occurring at the level of a single molecule. For further details contact Dr Sergi Garcia-Manyes .