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Luana Fioriti

Mario Negri Institute for Pharmaceutical Research
Milan

Molecular mechanisms for the perpetuation of memory storage

2006-2007

I received a Laurea in Scienze Biologiche from the Università degli Studi di Milano in 2001, where I was trained in Molecular Biology. I received a Specialisation in Biotechnology from the same university in 2004 and a PhD in Pharmacology from the Open University, London, in 2006. From 2001 to 2006 I have been working on molecular and cellular aspects of Familial Prion Disease which affect humans, like Creutzfeld Jacob Disease and Gerstmann-Straussler-Scheinker Syndrome, in an attempt to clarify the crucial steps for the appearance of these fatal pathologies, and possibly identifying a cure. My interest in prion molecules made me contact Prof. Eric Kandel, who recently hypothesized that a prion mechanism might be responsible for the persistence of long-term memory (Si et al, 2003). A protein called cytoplasmic polyadenylation element-binding protein (CPEB), a regulator of local protein synthesis, exists in a particular form in the nervous system of Aplysia and stabilizes newly formed synaptic connections. The first 150 amino-acids of CPEB constitute a domain that is very similar to that of prions. Like prions, CPEB can exist in two conformationally distinct isoforms but only one is metabolically active--the dominant form, characterized by an aggregate state. During my stay at the Italian Academy I will test the idea that these aggregates bind to dormant mRNA (ribonucleic acid messenger) resident at the synapse and modify them in order to be translated and give rise to proteins that stabilize synaptic growth. I also plan to examine if the prion domain of CPEB leads to a self-perpetuating level of local translation in neurons and if this novel mechanism leads to the stabilization of learning-related synaptic growth and the persistence of long-term memory and I will try to identify molecules that interact with CPEB and explore how this interaction leads to the activation of dormant mRNA or the conformational changes of CPEB at the neuronal synapse.