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Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectors

病毒工具开发核心：重组病毒载体对脑液动力学的可视化和操纵

基本信息

批准号：
10516500
负责人：
Hajime Hirase
金额：
$ 15.09万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10516500
关键词：
Affect Albumins Astrocytes Biomedical Research Biosensor Blood Blood - brain barrier anatomy Blood Vessels Blood flow Brain Brain imaging Breeding CRISPR/Cas technology Capsid Cells Cerebrospinal Fluid Cerebrovascular Circulation Chronic Complement Cyclic AMP Data Analyses Data Science Core Dependovirus Dermatology Documentation Engineering Ependymal Cell Genes Goals Hepatocyte Human Image Imaging Device Immune response Inflammation Injections Intercellular Fluid Ischemia Knock-in Label Liquid substance Liver Malignant Neoplasms Measurement Mediating Methods Molecular Nephrology Neuroglia Neurons Optics Peptide Signal Sequences Pharmacogenetics Physiologic Monitoring Physiological Plasma Process Production Proteins Publications Published Comment Recombinants Reporting Research Resource Sharing Resources Rodent Second Messenger Systems Signal Transduction Sleep Specificity Structure of choroid plexus TNFSF5 gene Techniques Technology Test Result Testing Time Toxic effect Tracer Transgenic Mice Variant Viral Viral Vector Visualization Visualization software adeno-associated viral vector base brain circulation capillary bed cell type cerebrospinal fluid flow cholinergic cost design experimental study genome editing imaging study in vivo in vivo evaluation innovation interest intravenous injection minimally invasive neural circuit neurotransmission neurovascular unit new technology noradrenergic novel optical imaging programs promoter receptor recombinant viral vector relating to nervous system serial imaging solute tool tool development vector

项目摘要

Viral Tool Development Core - Abstract Expression of genetically encoded biosensors and cell-type-specific opto-/pharmacogenetic manipulation represent effective approaches to reveal the mechanisms behind brain fluid dynamics during sleep. Most current technologies for labeling brain circulation are invasive and alter dynamics of cerebrospinal fluid (CSF) flow. The Viral Tool Development Core will develop novel, minimally-invasive methods to transform the study of CSF flow. The Core will support Projects 2 and 3 by providing viral vectors designed to label key fluid compartments, specifically interstitial fluid, CSF, and blood. This will be achieved by a combination of capsids, promoters, signal peptides, and gene traps in the case of adeno-associated viral vector (AAV). Other recombinant viral vectors will be designed as needed. In Aim 1, we will swiftly establish a viral tool development pipeline to provide in vivo verified viral vectors that will be optimized and validated. In Aim 2, we will engineer a set of viral tools that will express fluorescent albumin by transfecting the liver, allowing longitudinal vascular imaging after a single intravenous injection. In Aim 3, we will extend the utility of the blood probe by attaching biosensors or photo- activatable fluorescent proteins to report blood conditions or visualize CSF. In Aim 4, we will engineer a knock- in AAV vector to incorporate successful probes for permanent expression. The virally mediated expression of the innovative probes will allow for longitudinal imaging in existing transgenic mice without a need for further breeding, hence provides cost- and time-effective solutions for this research program. While the core will closely interact with Projects 2 and 3, the in vivo testing results for novel viral vectors will be shared and analyzed with the Data Science Core for comparisons with conventional probes. New probe ideas will be discussed with all research teams to determine the critical measurements that optical imaging can provide particularly from theoretical (Project 1) and human brain (Project 4) viewpoints.

病毒式工具开发核心-摘要