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Principal Investigator: Jennifer Kong
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2024
Award: $57,849
Funding agency: National Institute of General Medical Sciences
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.
Terms: <Address><Applications Grants><Assay><Bioassay><Biochemistry><Biological Assay><Biological Chemistry><Cell Body><Cell Communication and Signaling><Cell Culture Techniques><Cell Signaling><Cell surface><Cells><Chaperone><Cholesterol><Cilia><Complex><Cues><Data><E3 Ligase><E3 Ubiquitin Ligase><Embryo Development><Embryogenesis><Embryonic Development><Embryonic Tissue><Erinaceidae><Funding><Genetics-Mutagenesis><Grant Proposals><Hedgehog (Hh) signal transduction pathway><Hedgehogs><Integral Membrane Protein><Intracellular Communication and Signaling><Intrinsic Membrane Protein><Investigators><Learning><Molecular><Molecular Chaperones><Mutagenesis><Mutagenesis Molecular Biology><Postbaccalaureate><Process><Proteins><Protocol><Protocols documentation><Research><Research Personnel><Research Training><Researchers><Role><SHH><SHH gene><Signal Transduction><Signal Transduction Systems><Signaling><Sonic Hedgehog><Talents><Technical Expertise><Transducers><Transmembrane Protein><Transmembrane Protein Gene><Ubiquitin Protein Ligase><Ubiquitin-Protein Ligase Complexes><Ubiquitin-Protein Ligase E3><Universities><Washington><Work><biological signal transduction><career development><cell culture><cell cultures><computer based prediction><differentiation factors><embryo tissue><extracellular><graduate school><graduate school preparation><hedgehog signaling><hedgehog signaling pathway><hh signaling pathway><meeting><meetings><morphogenic factors><morphogens><parent grant><postbac><postbacc><posters><predictive modeling><regenerate new tissue><regenerate tissue><regenerating damaged tissue><regenerating tissue><smoothened signaling pathway><social role><success><technical skills><tissue regeneration><tissue regrowth><tissue renewal><tissue specific regeneration><ubiquitin-protein ligase><undergrad><undergraduate><undergraduate student>