We are testing a new system for linking grants to scientists.
The funding information displayed below comes from the
NIH Research Portfolio Online Reporting Tools and the
NSF Award Database.
The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
You can help! If you notice any innacuracies, please
sign in and mark grants as correct or incorrect matches.
Sign in to see low-probability grants and correct any errors in linkage between grants and researchers.
High-probability grants
According to our matching algorithm, Colenso M. Speer is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2020 |
Speer, Colenso Mcnaughton |
DP2Activity Code Description: To support highly innovative research projects by new investigators in all areas of biomedical and behavioral research. |
A Molecular Connectomics Platform For Multi-Scale Analysis of Activity-Dependent Synapse Development and Plasticity @ Univ of Maryland, College Park
Project summary/abstract Understanding brain function and plasticity requires innovative approaches for studying local (synaptic) molecular mechanisms that establish neural circuits (connectomes) underlying cognition and behavior. Here we propose a ?molecular connectomics? approach that integrates cell-type-specific transcriptomic, proteomic, super-resolution structural imaging, and optogenetic functional analyses to investigate the role of local protein translation in connectome development. We will pilot our approach by studying the activity-dependent development of the retinogeniculate pathway, which links retinal ganglion cells (RGCs) with postsynaptic neurons in the dorsal lateral geniculate nucleus (dLGN) for conscious visual perception and behavior. Working with a transgenic mouse line (ET33-Cre) in which eye-specific RGCs are genetically accessible, we will quantify molecular (1), structural (2), and functional (3) synaptic changes during eye-specific connectome development. The postnatal development of eye-specific pathways is regulated by retinal activity, allowing us to use transgenic and pharmacological tools to disrupt RGC spiking and further quantify activity-dependent changes in local protein synthesis mechanisms driving eye-specific synapse development and plasticity. Molecular analyses (1) will use axon-TRAP to immunoprecipitate eye-specific synaptic mRNAs (local synaptic translatomes) for next-generation sequencing. Local mRNA abundance/diversity will be further validated using multi-round fluorescence in-situ hybridization and mRNA barcoding for spatial transcriptomic imaging analysis. We will quantify the local synaptic proteome using proximity-labeling and non-canonical amino-acid labeling techniques to tag and isolate synaptic protein networks for quantitative high-resolution mass spectrometry. Proteomes will be validated using super-resolution structural imaging methods. Structural analyses (2) will map the molecular refinement of retinogeniculate connections using two super-resolution imaging techniques: volumetric STochastic Optical Reconstruction Microscopy (STORM) and Expansion Microscopy (ExM). These methods will be used to quantify protein and mRNA distributions in large, circuit-level tissue volumes with subsynaptic resolution. Functional characterization eye-specific synapses (3) will be performed using channelrhodopsin-mediated optical stimulation of eye-specific axons with postsynaptic recording in dLGN cells. Post hoc super-resolution microscopy of recorded neurons allows for direct, correlative measurement of structure/function relationships underlying activity-dependent changes in synaptic strength. This work will establish a novel methodology ? molecular connectomics ? to link local mRNA translation mechanisms in subcellular compartments with connectome assembly and refinement. Transcriptomic/proteomic analyses will help identify differentially-regulated gene/protein candidates for future gain/loss-of-function experiments. Our long-term goal is the application of our platform to identifying molecular mechanisms of circuit dysfunction in animal models of neurodevelopmental disorders and mental illness.
|
0.987 |