Centrioles are essential for the formation of several microtubule organizing structures including cilia, flagella and centrosomes. These structures are involved in a variety of functions, from cell motility to division. Centrosome defects are seen in many cancers, while abnormalities in cilia and flagella can lead to a variety of human diseases, such as polycystic kidney disease. The molecular mechanisms regulating centriole biogenesis have only recently started to be unravelled, opening new ways to answer a wide range of questions that have fascinated biologists for more than a century. In this grant we are asking two fundamental questions that are central to human disease: how is centriole structure and number established and regulated in the eukaryotic cell? To address these questions we propose to identify new molecular players, and to test the role of these and known players in the context of specific mechanistic hypothesis, using in vitro and in vivo models. We propose to develop novel assays for centriole structure and regulation in order to address mechanistic problems not accessible with today s assays. In our search for novel components we will use a multidisciplinary approach combining bioinformatics with high throughput screening. The use of in vitro systems will permit the quantitative dissection of molecular mechanisms, while the study of those mechanisms in Drosophila will allow us to understand them at the whole organism level. Furthermore, this analysis, together with studies in human tissue culture cells, will allow us to understand the consequences of misregulation of these fundamental centriole properties for human disease, such as ciliopathies and cancer. My group is already collaborating with medical doctors in the study of centriole aberrations in human disease (cancer and ciliopathies), which will be invaluable to bringing the results of this study to the translational level.
Field of science
- /medical and health sciences/clinical medicine/oncology/cancer
Call for proposal
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