Fabrizio Chiti

Biography

Fabrizio Chiti graduated in Biological Sciences in 1995 at the University of Florence and received a Ph.D. in Chemistry at Oxford University in 1999. His research activity, under the supervision of Prof. C.M. Dobson, covered the protein folding this time. His post-doctoral research activity, carried out in the field of protein aggregation and amyloid fibril formation, was conducted at the University of Florence for two years under the guidance of Prof. G. Ramponi and then at the University of Cambridge for 1 year, still under the guidance of Prof. CM Dobson. Fabrizio Chiti has been Associate Professor of Biochemistry from 2002 to 2010 and is now Full Professor at the Department of Biomedical and Experimental Biomedical Sciences, Department of Biochemical Sciences, University of Florence.

Research Interest

Proteins have a generic tendency to convert from their soluble states into insoluble highly structured aggregates known as amyloid fibrils. Since these aggregates are toxic to the cells, especially in the form of early forming oligomers, cellular machinery has evolved, among other requirements, to inhibit uncontrolled protein aggregation. Failure to inhibit protein aggregation often results in pathology. To date, a large number of very diverse human diseases, including Alzheimer's, Parkinson's and Type II diabetes, have been recognized as being associated with the formation of amyloid fibrils or protein inclusions with amyloid-like properties. Amyloid fibril formation is also exploited by living organisms for the formation of fibrillar structures with specific biological functions, provided that this occurs under controlled conditions. Finally, the recent findings that the inclusion bodies formed after overexpression of heterologous proteins in bacteria are amyloid-like in structure and the increased awareness that a huge number of novel materials based on the amyloid motif can be constructed has expanded the interest of amyloid formation to biotechnology. The research of this lab uses a multi-angle approach to investigate the mechanisms by which soluble proteins are assembled into ordered aggregates and by which the resulting aggregates cause cell dysfunction. Here is a list of past and ongoing projects: Study, at a molecular level, of the process by which native proteins convert to partially folded states necessary to initiate aggregation Study, in molecular depth, of the conversion of partially folded states of proteins into amyloid fibrils and their precursor oligomers Study of the relationship between the structure and toxicity of protein oligomers Investigation of molecular chaperones as inhibitors of the toxicity of protein oligomers Investigation of small molecules as inhibitors on the formation and toxicity of protein oligomers Study, at a molecular level, of the process of native-like aggregation, involving directly the folded state of a protein Study of the effect of agents of the extracellular matrix, such as glycosamynoglycans, on the formation of amyloid fibrils, precursor oligomers and their toxicity Editing of mathematical algorithms capable of predicting fundamental aspects of protein aggregation in vitro and in vivo Elucidation of protein oligomers on neuronal function of primary neurons and rat brains