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Principal Investigator: Naly Torres
Organization: COLORADO STATE UNIVERSITY
Fiscal Year: 2024
Award: $41,282
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY
This proposal outlines a training program for independent scientist with a focus on mRNA localization using
genetics and molecular biology. The research outlined in this proposal will develop a platform to evaluate local
translation, a process of whose disruption results in many neurological diseases and cancer. The phenomena
directing local translation to axon termini and the Endoplasmic Reticulum (ER) have been described. Scientists
have recently made the novel discovery that local translation also occurs at plasma membranes. For example,
in Caenorhabditis elegans, ezrin/radixin/moesin (erm-1) mRNA localizes to plasma membranes with its
encoded protein, a plasma membrane-actin cytoskeleton linker that will coordinate cell shape changes. erm-
1/ERM-1 undergoes translation-dependent localization and local translation directed by its N-terminal encoded
FERM domain. However, neither the mechanisms directing their localization nor the reasons for their local
translation are understood. The proposed research aims to use erm-1 as a model to understand how mRNA
localization to the plasma membrane arises mechanistically, functionally links to protein production, and
impacts gene expression. Based on preliminary evidence, the hypothesis is that cytoskeletal components
interact with the translating complex to direct it to the plasma membrane, similar to co-translational transport of
secretory proteins to the ER. This model will be explored from a genetics and molecular biology perspective
with 3 specific aims. The first aim will test whether erm-1/ERM-1 localization occurs through diffusion or
directed transport mechanisms and explore which cytoskeletal components are required. The second aim will
develop a live imaging tool to better resolve the kinetics of erm-1 translation. The third aim will identify the
effector proteins involved in this process. Since impaired mRNA localization in neurons and other cell types
causes disease but studying mRNA localization in disease-specific models is challenging, this project will
achieve our long-term goal of characterizing novel mRNA transport pathways that have the potential to be
generalizable in human health.
Terms: <Actins><Active Biologic Transport><Active Biological Transport><Active Transport><Address><Affect><Automobile Driving><Axon><Bio-Informatics><Bioinformatics><Biologic Models><Biological Models><C elegans><C. elegans><C.elegans><Caenorhabditis elegans><Cell Body><Cell Shape><Cell membrane><Cells><Cellular Matrix><Cellular Morphology><Co-Immunoprecipitations><Complement><Complement Proteins><Complex><Cytoplasm><Cytoplasmic Membrane><Cytoskeletal System><Cytoskeleton><DNA Molecular Biology><Diffusion><Disease><Disorder><Drug Therapy><Drugs><ERM protein><ETV5 protein><Embryo><Embryonic><Endoplasmic Reticulum><Ergastoplasm><Ets-related molecule PEA3-like protein><Event><FISH Technic><FISH Technique><FISH analysis><FISH assay><Fluorescence In Situ Hybridization><Fluorescence Photobleaching Recovery><Fluorescence Recovery After Photobleaching><Fluorescent in Situ Hybridization><Foundations><Gene Expression><Genetic><Goals><Granular Endoplasmic Reticulum><Health><History><Human><Human Cell Line><Image><Imaging Device><Imaging Instrument><Imaging Procedures><Imaging Technics><Imaging Techniques><Imaging Tool><Immunofluorescence><Immunofluorescence Immunologic><Impairment><Investigators><Kinetics><Knowledge><Lab Findings><Laboratory Finding><Learning><Link><Locales><Malignant Nervous System Neoplasm><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Medication><Membrane><Messenger RNA><Methods><Micro-tubule><Microtubules><Model System><Modeling><Modern Man><Molecular Biology><Motor><N-terminal><NH2-terminal><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neurologic Disorders><Neurological Disorders><Neurons><Pathway interactions><Peptide Domain><Peptides><Permeability><Pharmaceutical Preparations><Pharmacotherapy><Phosphorylation><Plasma Membrane><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Process><Production><Protein Domains><Protein Phosphorylation><Protein Trafficking><Proteins><RNA Interference><RNA Silencing><RNAi><Recording of previous events><Reporter><Research><Research Design><Research Personnel><Researchers><Ribosomes><Rough ER><Rough endoplasmic reticulum><Rough-Surfaced Endoplasmic Reticulum><Scientist><Sequence-Specific Posttranscriptional Gene Silencing><Site><Study Type><Survey Instrument><Surveys><Techniques><Tertiary Protein Structure><Testing><Time><Training Programs><Translating><Translation Initiation><Translations><Uphill Transport><Visualization><Work><cell morphology><cell type><complementation><diffused><diffuses><diffusing><diffusions><driving><drug treatment><drug/agent><experience><ezrin><histories><imaging><imaging system><intracellular skeleton><mRNA><malignant nervous system tumor><malignant neurologic neoplasms><membrane structure><membrane-organizing extension spike protein><moesin><neurological cancers><neurological disease><neuronal><novel><pathway><phosphoprotein p81><plasmalemma><protein transport><radixin><radixin protein><secretory protein><single molecule><study design><tech development><technology development><tool><trafficking><translation>