To complete and diversify her scientific expertise, Dr. Ianari has decided to join Dr. Lees' lab, a leading lab located in a top-level research organization (MIT¿ USA). The aim of her project is to study the role of E2F1 acetylation in the DNA damage response and in the development and homeostasis of the normal tissues. E2F1 is a transcriptional factor that possess both oncogenic and tumour suppressive functions. The spectrum of E2F1-regulated genes is quite large and comprises genes involved in the regulation of development, differentiation, cell cycle progression and apoptosis. Dr. Ianari has recently demonstrated that DNA damage specifically activates E2F1 apoptotic potential in an acetylation-dependent manner by the selective relocalization of transcriptionally active E2F1 from cell cycle genes to the promoter of the proapoptotic p73 gene. Indeed, E2F1 acetylation is the main determinant of the outcome of E2F1 activity in response to DNA damage. Whether this pathway is specifically restricted to maintain tissue homeostasis in the presence of unrepairable DNA damage, or is involved in additional cell regulatory functions, is presently unknown.
The aim of this project is to use a gene targeting approach to generate a mouse strain that produces a version of E 2F1 that cannot be acetylated but is otherwise regulated physiologically. Dr. Ianari will combine highly innovative and sophisticated techniques (knock-in mouse model generation, chromatin immuno-precipitation and micro-array analysis) and multidisciplinary approaches (developmental biology, molecular biology and experimental oncology), to provide insight into the underlying mechanisms of tumour development that will aid the development of new selective cancer therapies. This experience will advance Dr. Ianari' s independent career development in two ways: she will gain additional knowledge both in scientific and technological terms, and it will provide her with long-lasting scientific collaborations.
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