PROJECT SUMMARY/ABSTRACT This is a proposal for a Diversity Supplement to fund research training and career development for Dorothy Lartey, a talented undergraduate student and soon postbaccalaureate researcher in the Kong Lab at the University of Washington. The parent grant for this proposal is 4R00GM132518-03, which focuses on understanding the mechanisms that modulate a cell’s sensitivity to morphogens. Dorothy’s research involves understanding the function of MOSMO, a ciliary tetraspan that establishes a cell’s sensitivity to the morphogen Sonic Hedgehog (SHH). While we know that MOSMO forms a complex with MEGF8 (a single-pass transmembrane protein) and MGRN1 (an E3 ubiquitin ligase) to regulate Smoothened (SMO, a core transducer of the Hedgehog signaling pathway), its role in this process remains unresolved. To address this, Dorothy will specifically examine the MOSMO/MEGF8 interaction and its ciliary localization, assessing both their roles in regulating Hedgehog signaling activity. Aim 1 focuses on dissecting the MOSMO/MEGF8 interaction, using predictive models to disrupt the interaction and study subsequent effects on the localization of SMO and Hedgehog signaling. Aim 2 focuses on MOSMO localization, generating constructs that do not localize to the cilia and utilizing these to understand its role in regulating SMO. Lastly, Aim 3 examines the role of cholesterol in regulating the activity of MOSMO. These proposed studies will advance our understanding of how the MOSMO/MEGF8/MGRN1 (MMM) complex works and how target cells regulate their sensitivity to extracellular cues. Through this project, Dorothy will learn many new technical skills to prepare her for graduate school, including signaling assays and cell culture protocols. In addition, Dorothy will learn how to organize her data and present her work as a poster at multiple meetings. Collectively, this supplement will prepare Dorothy for success in biochemistry research in the form of graduate school and beyond.