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High-probability grants
According to our matching algorithm, Jordane Dimidschstein is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2018 |
Dimidschstein, Jordane |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mapping and Controlling Gene Expression in Inhibitory Interneurons Mammals
Project Summary: Fundamental to furthering our understanding of the brain is the ability to longitudinally track changes in gene expression over time in different contexts (e.g. development or learning) (Aim 1) and to develop methods to target and manipulate specific neuronal cell types regardless of species (Aim 2). This proposal is aimed at achieving these goals in both genetically amenable and non-amenable species. While we anticipate that the methodologies we will develop will be broadly useful in a multitude of contexts, we will leverage our experience and knowledge of the specification and development of interneurons as a means to validate our approaches. Forebrain interneurons are a particularly robust context to develop these methods because the circuits interneurons contribute to during development are both dynamic and transient. This makes them a particularly attractive target for exploring longitudinal gene expression (Aim 1). This will be achieved using a modification of the DamID method, which we have redesigned to make inducible at particular developmental timepoints. Moreover, the diversity within this population is considerable, making them an ideal target for exploring methods to efficiently target subpopulations without the need for transgenic tools (Aim 2). In this aim we will leverage transcriptome data sets, including data produced in Aim1. Utilizing a computational program identify enhancer elements for mediating directed gene expression in rAAVs. Viruses produced in this aim will be validated for use in mice and less genetically amenable species, including non-human primates.
|
0.982 |
2019 — 2021 |
Deverman, Benjamin E (co-PI) [⬀] Dimidschstein, Jordane Fishell, Gordon J |
UG3Activity Code Description: As part of a bi-phasic approach to funding exploratory and/or developmental research, the UG3 provides support for the first phase of the award. This activity code is used in lieu of the UH2 activity code when larger budgets and/or project periods are required to establish feasibility for the project. |
Development and Validation of Aav Vectors to Manipulate Specific Neuronal Subtypes and Circuits Involved in Epilepsy and Psychiatric Disorders Across Mammalian Species.
PROJECT SUMMARY In this proposal we aim to identify gene regulatory elements that permit the targeting and manipulation of brain circuit models of human brain function. Gaining genetic access to specific neuron populations in nontransgenic animals and humans would enable targeted circuit modulation for hypothesis testing and provide a means to evaluate the safety and efficacy of circuit modulation for the treatment of epilepsy and psychiatric disorders. Our approach capitalizes on our combined expertise in the development and maturation of brain cell-types and circuits (Gord Fishell), identification of CIS-regulatory elements that function across species (Jordane Dimidschstein) and AAV engineering combined with large-scale screening methods (Ben Deverman). Our efforts will benefit from an ongoing collaboration with John Reynolds at the Salk Institute on observation and manipulation of cortical circuits during complex visual perception tasks. This project will build upon success that we and others have had in identifying gene regulatory elements that enable cell type-restricted gene expression when used within recombinant adeno-associated virus (AAV) vectors. Identifying additional enhancer sequences that function in the context of the limited carrying capacity of AAV has been slow due to the limited success rate and low throughput nature of these efforts. Here we aim to apply a novel high-throughput screening approach for the rapid identification of a suite of enhancers that enable the study and manipulation of genetically defined cell types and circuits across species. Our preliminary data demonstrates that our enhancer identification strategy can yield novel and highly specific enhancers that restrict expression to target populations. In addition, we have demonstrated that it is possible to use the engineered AAV-PHP.eB capsid to screen enhancers across the brain with a single noninvasive injection. These successes have highlighted the need for more rapid and comprehensive assessment of putative enhancers. In the UH3 portion of this proposal we will examine the tolerance to neuronal activity manipulation within the target neuronal populations in several species. We will also apply the AAV-enhancer viruses for querying disease-related circuits using Rabies tracing in conjunction with optogenetics. This proposal will be transformative in devising methods to target and manipulate the brain activity of specific neuronal cell populations across species, including human cell-derived organoids.
|
0.982 |