The Ruth K. Broad Foundation Seminar Series on Neurobiology and Disease at Duke University seeks to promote Translational Neuroscience by facilitating the interactions of fundamental and clinical neuroscientists. Translational Neuroscience applies insights gained through fundamental research on brain structure and function to develop novel pharmacological, surgical, and behavioral therapies of these diseases. This seminar series will feature national and international neuroscientists of the highest caliber. Neuroscientists from Duke and other academic institutions, government, and pharmaceutical and biotechnology institutions throughout the region are welcome to attend.
To facilitate access of an even broader audience, the seminars will be recorded, digitized, and posted on this web site, thereby giving neuroscientists worldwide access to this valuable resource. This lectureship series is made possible by the generous support of the Ruth K. and Shepard Broad Biomedical Research Foundation.
Systems genomics and gene networks in neuro- developmental and neurodegenerative disorders
October 10, 2018
Abstract: Advances in genetics and genomics have begun to deliver on their promise to expand our understanding of nervous system function in health and disease. One of the interesting challenges that perhaps paradoxically has emerged from these successes is an understanding of the profound genetic heterogeneity and complexity of most nervous system disorders. For example in Autism Spectrum Disorder (ASD), over a hundred of probable risk loci have been identified, none of which account for more than 1% of cases. This has led to what we consider to be a central question highly relevant to precision health approaches: will we have to treat each rare genetic form as a unique condition, or will there be convergence on a smaller number of shared pathways? I will highlight advances in the genetics of ASD and discuss integrative genomic approaches such as genome-wide transcriptional profiling that inform this important issue and that do suggest a substantial level of convergence. These studies provide a quantitative framework for functional investigation of disease mechanisms with a goal of accelerating therapeutic development.
Dissecting synaptic and circuitry mechanisms of psychiatric disorders
October 23, 2018
Abstract: Synaptic dysfunction has emerged as a key pathology in several psychiatric disorders including autism spectrum disorders (ASD) schizophrenia. Recently, large scale human genetic studies have also revealed a significant overlaps of risk genes for schizophrenia, bipolar disorder and autism. However, it is not clear how different mutations of the same gene could contribute to the manifestation of different diseases. Using the postsynaptic scaffolding protein Shank3 as an example, Dr. Feng will discuss: (1) circuitry mechanisms of repetitive behaviors in mouse models of ASD; (2) reversibility of synaptic, circuitry and behavioral abnormalities in adult mouse models of ASD; (3) shared and distinct synaptic and behavioral phenotypes in two lines of Shank3 mutant mice linked to ASD and schizophrenia.
February 5, 2019
Beginning with genes that are disrupted in patients with neurodegenerative diseases, Taylor's lab team first determines the normal function of those genes and then looks at how their mutation causes disease, taking advantage of any model or experimental system that gets the researchers closer to an answer. This strategy has led Taylor to discover that some neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia, are caused by defects in the assembly, disassembly, or clearance of cellular packages of RNA and protein known as RNA granules. He has shown that these types of defects in RNA metabolism can also cause degenerative muscle diseases. Taylor's team is now investigating the role of RNA granules in regulating gene activity and exploring how the granules are assembled.
February 12, 2019
A synapse, the point of contact and communication between neurons, is one of the smallest fundamental circuits available for analysis in the brain. The brain generates representations of environmental inputs received from sensory systems and must constantly update these representations to effectively interact with a changing environment. The ability of the nervous system to respond adaptively relies on modifications to existing proteins as well as changes in gene transcription, protein synthesis, and protein degradation. In addition, there are transynaptic signals generated via the regulation of adhesion molecules resident at synapses. We are interested in how these cell biological mechanisms transmit information and modify circuits to store information. We conduct many of our studies in the rat hippocampus, a structure known to be important for memory in both humans and animals. We have also recently initiated studies using zebrafish as a system to study memory at the molecular, cellular and behavioral levels. We use the tools of molecular biology, electrophysiology and imaging to address the various experimental questions in the lab.
May 7, 2019
Research in my lab focuses on the general question of how experience acts on the nervous system to shape behavior. Our goal is to account for learning by understanding the sensory stimuli that drive change, how and where those stimuli are represented in patterns of neural activity, and how those patterns act to modify behavior. We hope both to reveal general learning mechanisms, and to understand how variations in those mechanisms give rise to individual differences in behavior. Hence, we are interested in how the nervous system changes over the course of development to give rise to 'critical periods' for learning and how innate variations between individuals interact with experience to give rise to differences in learned behaviors. Towards this end, we employ a variety of behavioral, neurophysiological and genetic approaches to investigate vocal learning in songbirds.
June 4, 2019
The lab’s goal is to understand the interplay of membrane-bound organelles, cytoskeletal structure, and metabolism as it relates to the organization and function of neurons, and the cells they interact with. On a small scale, we are interested in mapping out the spatial organization, stoichiometry, and dynamics of proteins as they interact with each other and with different parts of the cell. On a larger scale, we are trying to decipher how complex cellular behaviors arise, including cell crawling, polarization, cell-cell contact, cytokinesis, cell fate determination, viral budding, and intercellular transfer. To study these problems, we rely heavily on microscopy – including super-resolution imaging techniques and cutting edge fluorescence-based technologies – as well as biochemistry, in vitro reconstitution, and mathematical modeling.