As a tumour grows, it stops scaling properly—a hand that kept pace with a growing body suddenly becomes a hand that doesn’t fit, and the same loss of proportion happens inside cancerous tissue. This project investigates why. During normal development, organs and tissues maintain precise size relationships: your hands scale with your body, your organs with each other. In cancer, that scaling machinery breaks down. The researcher has already identified two key molecules—TGF-Beta and SMOC1/2—that help control this scaling in fruit flies. Now they want to see whether the same mechanism goes wrong in human tumours. If the work succeeds, it will reveal a completely unexplored cause of uncontrolled tumour growth: the failure of a “death-mediated scaling” process that normally keeps tissue proportions in check. That could open the door to new strategies for impairing tumour growth, though the research is still at a fundamental stage. The project is primarily curiosity-driven, building on principles of developmental biology. Similar fundamental work on morphogen gradients has previously transformed our understanding of how embryos pattern themselves, and this line of inquiry could eventually do the same for cancer biology.
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The question. Remarkably and despite of the increase in size in human development, during growth, morphological patterns in our bodies keep proportional: e.g. the size of our hands scales with the length of our developing body. However, the system can be hijacked leading to diseases such as cancer where these proportionalities are no longer preserved. Understanding how organs and tissues tune the scaling machinery during tumorigenesis remains a challenging biological issue. TGF-Beta (Dpp homolog) and SMOC1/2 (Pentagone homologs), key factors of the scaling machinery have been shown to be involved in tumorigenesis. Specific Objectives. My goal now, is to explore this mechanism in overgrowth conditions. We will capitalize on the Dpp scaling principles found by me and other groups, together with my unpublished work to explore this mechanism in overgrowth conditions. I expect to address four key questions: i)Characterisation of Pent expression in tumorigenesis. ii)Analyses of Dpp Gradient Scaling during tumorigenesis. iii)Pentagone Death and Scaling Control during tumorigenesis. iv)Spatial and Temporal Dynamics of TGF-beta and SMOC in human tumorigenesis. AMS-Springboard-Impact. Characterisation of Death-mediated-scaling during tumorigenesis, will be a breakthrough, revealing the bases of tumoral growth from a novel and unexplored mechanism. Giving the proposed collaborations with Clinical Research, these analyses might pave the way to developing new strategies to impair tumoral growth. Furthermore, the AMS-Springboard-award will allow me to place my research profile in a privileged position to secure the most competitive funding and establish myself as a world leader in the field of morphogens and tumoral growth.
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