Deep mutagenesis to understand Protein Phase Transitions

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Online IBEC Seminar with Benedetta Bolognesi


BIST IBEC B Bolognesi

Benedetta Bolognesi , IBEC

Specific insoluble protein aggregates are the hallmarks of many neurodegenerative diseases. Whether the protein aggregates themselves or other forms of the proteins are toxic to cells is still unclear in many of these diseases. This lack of understanding of the causes of cellular toxicity is reflected in the general failure of multiple therapeutic approaches so far attempted. The causes of this rely mainly on the lack of systematic approaches able to estimate in parallel the effect of mutations on cell viability as well as on protein conformation. Our lab uses deep mutagenesis as a systematic and unbiased approach to identify and investigate the toxic species of proteins.

In this seminar I will explain how we used this approach to report on the toxicity of thousands of protein sequences and how, more recently, we adapted this method to track more specific biochemical processes, such as amyloid nucleation. Overall, the results I will discuss demonstrate that deep mutagenesis is a powerful approach to study intrinsically disordered proteins and also illustrate that it can be used to genetically validate assays as discovery platforms.

The seminar will take place online at the GoToMeeting Platform

Know more about Benedetta Bolognesi’s research here