Principal Investigator: Sacha B. Nelson
Title: Combining genetics, genomics, and anatomy to classify cell types across mammals”
BRAIN Category: Census of Cell Types (RFA MH-14-215)
To gain a deeper understanding of how cells have evolved specialized features, Dr. Nelson and colleagues will create transgenic strains of rats and mice that carry identical genetic modifications in many different cell types and see how the properties of these cells diverge across species.
Recent genetic advances have driven significant progress in scientists’ abilities to classify and map neuronal cell types within the brains of mode organisms like laboratory mice. To better delineate neuronal cell types in the human brain, however, it is critical to have a deeper understanding of the way that neuronal cell types evolve across mammals. As a first step toward achieving this understanding, corresponding neuronal cell types will be directly compared in two closely related mammalian species: mice and rats. By closely examining differences in the properties of these cells, including the genes they express, we hope to identify genomic elements that control the properties of neuronal cell types, and to infer properties of the corresponding cell types in the human brain. Improving the precision with which we can classify human neuronal cell types could have a transformative impact on our ability to understand pathological changes in neuropsychiatric disease.
NIH Spending Category
Drug Abuse (NIDA only); Genetics; Human Genome; Mental Health; Neurosciences; Substance Abuse
Accounting; Algorithms; Anatomy; Area; Atlases; Axon; base; Brain; Brain region; cell body (neuron); cell type; Cells; Chromatin; Classification; Collaborations; Complement; Data; Data Set; density; design; Disease; Elements; Enhancers; Evolution; frontal lobe; Gene Expression; Gene Expression Profile; Genes; Genetic; genome-wide; Genomics; Health; homologous recombination; Human; improved; Interneurons; Knock-in Mouse; Knowledge; Laboratory mice; Location; Logic; mammalian genome; Mammals; man; Maps; Mental disorders; Methods; Molecular; Morphology; Mus; nerve supply; nervous system disorder; Neuroanatomy; Neurons; neuropsychiatry; neurotransmitter release; novel; Nucleic Acid Regulatory Sequences; Organism; Pattern; Phenotype; Physiological; Physiology; Population; postsynaptic; presynaptic; Presynaptic Terminals; Problem Solving; Property; Prosencephalon; Proteins; public health relevance; Rat Strains; Rattus; Regulatory Element; Reporter; Resolution; Scientist; Site; Slice; Sorting – Cell Movement; species difference; Structure; Synapses; Synteny; Testing; Work; XCL1 gene
Public Health Relevance Statement
PUBLIC HEALTH RELEVANCE: Health Relevance Narrative Perturbations in the structure and function of neuronal cell types in the human brain can cause neuropsychiatric diseases, but our knowledge of these cell types is incomplete. In order to better understand the neuronal cell types that make up the human brain, it is necessary to understand the similarities and differences between corresponding cell types across different mammalian species. This project will study this problem for corresponding cell types in two closely related species: mice and rats.