Project Summary The common marmoset (Callithrix jacchus) has experienced unprecedented growth in research across the United States and is rapidly emerging as a likely keystone biomedical model system in the next chapter of scientific discovery.
PROJECT SUMMARY/ABSTRACT The common marmoset (Callithrix jacchus) has emerged as a critically important and tractable non-human primate (NHP) model for neuroscience research accommodating genetic manipulation and directed breeding. Several barriers to the adoption of marmoset models by the neuroscience community exist, including a small census size in the United States (fewer than 2,500 animals), poor communication about resource availability, a poor understanding of the strengths and limitations of marmosets in research, and a lack of a formal structure for coordinating the sharing of info
Project Summary We propose to leverage new and existing transcriptomic and epigenetic datasets from mouse, marmoset, macaque and human brain to develop refined approaches for brain cell type enhancer selection for creating cell- type specific enhancer adeno-associated viruses (AAVs), and to make inroads toward prediction of brain-wide expression specificity.
Systematic experimental access to diverse neuronal cell types is a prerequisite to deciphering brain circuit organization, function, and dysfunction. Thus fundamental progress in neuroscience urgently needs cell type access technologies that are specific, comprehensive, easy to use, affordable, scalable, and general across animal species. Most if not all current genetic approaches to cell type targeting are based on genome and DNA engineering, which has inherent limitations in achieving the desired tool features.
PROJECT SUMMARY: This team initiative will provide the broad neuroscience community with a cell type-specific adeno- associated virus (AAV) armamentarium for easy and non-invasive implementation of novel and emerging molecular tools for anatomical and functional analysis of the nervous system in rodents, non-human primates, and human organoids. We will characterize engineered AAV capsids for cell type- and brain region-specific gene delivery (Aim 1).
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.
Project Summary The human brain contains an astonishing diversity of neuronal and glial cell types distributed across dozens of functional areas.
Adeno-Associated Viruses (AAVs) are potent gene delivery vectors for neuroscience studies and gene therapy applications. However, naturally occurring AAVs are not cell type specific: they must be combined with other technologies, such as transgenic animals, to achieve cell type specific gene expression.
ABSTRACT / SUMMARY New technologies are enabling molecular profiling of single brain cells at remarkable throughput. However, these new methods have yet to be extensively applied to the brains of model organisms that bridge the evolutionary distance between mouse and human, including the most common nonhuman primate model system - the rhesus macaque. Here we propose to generate an anatomically resolved, single cell atlas of the epigenome (5.5 million cells) and transcriptome (11 million cells) of the rhesus macaque brain.
Abstract Understanding the exact cell-type composition in the different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell-types present in the human brain have been defined through a handful of specific markers, the
