The Maness laboratory focuses on defining novel mechanisms for establishing neuronal connectivity in the developing mammalian brain using mouse models, molecular biology, and protein biochemistry. A key focus of the lab is understanding the molecular mechanism by which Neural Cell Adhesion Molecules (CAMs) regulated dendritic spines and synapses during the adolescent to adult transition. Genes encoding Neuron-Glial related CAM (NrCAM), L1, and NCAM are linked to autism, schizophrenia, and bipolar disorder, thus identification of their molecular action in developing cortical circuits will provide important insight into normal and pathological brain development.
We recently made important discoveries that CAMs are essential co-receptors for two classes of repellent ligands, Semaphorins and Ephrins. Newly generated mouse genetic mutants reveal that CAMs mediate synaptic pruning of both excitatory and inhibitory neurons during early postnatal life when appropriate E/I balance in cortical networks is established. Correct neural circuitry enables large-scale behaviors such as sociability, learning, and working memory to operate normally. Specifically, we found that NrCAM is an obligate component of a class 3 Semaphorin receptor complex (Neuropilin2, PlexinA3), which regulates dendritic spine pruning in the adolescent prefrontal and visual cortex. We also demonstrated that a different adhesion molecule, NCAM, is a key subunit of the ephrinA5 receptor EphA3, which limits the connectivity of GABAergic synapses in developing prefrontal cortex. These findings have widespread implications for understanding normal adolescent brain development and its pathology in brain disorders, yet much remains to be identified.
It is important to define the precise molecular action of CAMs in development and plasticity. This new NIH funded research project will entail characterizing the molecular composition and developmental role of the Sema3F and Ephrin receptor complexes using molecular modeling, mutagenesis, and protein-protein interaction experiments. The downstream signaling pathways for each receptor system will then be identified in cortical neuron cultures and invivo by in utero electroporation. To analyze the dynamics of spines and synapses in live neurons, advanced 2 photon live imaging will be conducted in brain slices derived from GFP-labeled normal and mutant mice. Behavior studies of working memory, sociability and learning will be conducted in conjunction with the UNC Mouse Behavioral Core.
The applicant will study with Dr. Patricia Maness (mouse genetic models, biochemistry) and interacting UNC faculty Dr. Paul Manis (2 photon microscopy, electrophysiology), Dr. Brenda Temple (structural modeling), and Dr. Sheryl Moy (Mouse Behavioral Core) to acquire specialized training in state-of-the-art techniques and complete the goals of the project.
The Maness laboratory in the Biochemistry Department is located in the Genetic Medicine Building of the UNC School of Medicine, with access to outstanding microscopy, imaging, and core facilities in the UNC Neuroscience Research Center and Carolina Institute for Developmental Disabilities. Our environment offers a rich venue for training in state-of-the-art developmental neuroscience and opportunities for enrichment.
The successful applicant will have a PhD degree with preferred expertise in neuroscience, cellular and molecular biology, and protein biochemistry. Specific experience in confocal microscopy, two photon live imaging of cells, or electrophysiology is a plus.
The position is available immediately.
Please send CV and list of three references to: Dr. Patricia Maness
Visit our website for further details: http://www.unc.edu/~srclab/
Additional Salary Information: Plus health insurance and social security benefits
About University of North Carolina School of Medicine
The Maness laboratory at UNC is in the Biochemistry Department located in the Genetic Medicine Building with access to outstanding imaging and core facilities in the UNC Neuroscience Research Center and Carolina Institute for Developmental Disabilities. The environment offers a rich venue for training in molecular developmental neuroscience.
The laboratory focuses on defining mechanisms regula...ting neuronal connectivity in the developing mammalian brain using novel mouse models, molecular biological approaches, and protein biochemistry. The project focuses on defining the role of Neural Cell Adhesion Molecules (CAMs) in regulating dendritic spine and synapse pruning during the adolescent to adult transition. Genes encoding NrCAM, L1, CHL1, and NCAM are targeted for mutation in neurodevelopmental disorders such as autism and schizophrenia, thus is it important to define their molecular function in developing cortical neurons.