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Cambridge Immunology Network

 

Research

The overall objective of our research is to understand the principles governing protein homeostasis - the ability of cells to generate and regulate the levels of proteins in terms of conformations, interactions, concentrations and cellular localisation. By adopting the strategy of analysing the origins of specific diseases to inform us about normal biology, we have set up an interdisciplinary programme that involves bringing together methods and concepts from chemistry, physics, engineering, genetics and medicine. We are using a combination of in vitro, in silico and in vivo approaches to study protein homeostasis through the analysis of the effects that result from its alteration in a select group of specific proteins, from either amino acid mutations, or changes in concentration and solubility, or the interactions with other molecules. This programme is generating new insights into the mechanism through which physical and chemical sciences can address biological questions in order to understand the normal behaviour of living systems. In addition it is increasing our understanding of the nature and consequences of the failure to maintain homeostasis, which is associated with such phenomena as ageing and neurodegenerative disorders.

Publications

Key publications: 

P. Sormanni, F. A. Aprile and M. Vendruscolo. Third generation antibody discovery methods: In silico rational design. Chem. Soc. Rev. 47, 9137-9157 (2018).

 

F. A. Aprile, P. Sormanni, M. Perni, P. Arosio, S. Linse, T. P. J. Knowles, C. M. Dobson and Michele Vendruscolo. Selective targeting of primary and secondary nucleation pathways in Abeta42 aggregation using a rational antibody scanning method. Sci. Adv. 3, e1700488 (2017).

 

P. Sormanni, F. A. Aprile and M. Vendruscolo. Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins. Proc. Natl. Acad. Sci. USA, 112, 9902-9907 (2015).

 

Carlo Camilloni, Aleksandr B. Sahakyan, Michael J. Holliday, Nancy G. Isern, Fengli Zhang, Elan Z. Eisenmesser, and Michele Vendruscolo (2014) Cyclophilin A catalyzes proline isomerization by an electrostatic handle mechanism Proc. Natl. Ac. Sci. vol. 111 28,  10203–10208.

 

Leung HT, Kukic P, Camilloni C, Bemporad F, De Simone A, Aprile FA, Kumita JR, Vendruscolo M. (2014) NMR characterization of the conformational fluctuations of the human lymphocyte function-associated antigen-1 I-domain. Protein Sci. 2014 Aug 21. doi: 10.1002/pro.2538. [Epub ahead of print]

Professor Michele  Vendruscolo
Takes PhD students
Not available for consultancy

Affiliations

Classifications: 
Departments and institutes: