Developmental Biology and Neurobiology
A central goal of life sciences research has been to understand how complex tissues and their substituent cells develop and function. Recent years have brought enormous advances in our ability to experimentally manipulate gene expression in cells, embryos and tissues, and to analyze subtle and complex phenotypes. The Neuroscience and Developmental Biology Group brings together laboratories using these advances to study the structure, function and growth of the nervous system and the mechanisms by which diverse tissues and organisms develop. Our members bring to bear on these problems the tools of molecular and cellular biology, advanced light microscopy, electrophysiology, transgenesis, mutagenesis and experimental embryology. We combine these tools with the power of several model genetic systems including zebra fish, mouse, Drosophila, yeast and Arabidopsis. Other organisms are used that are optimal for particular experimental approaches, including rat, guinea pig, chicken and Aplysia (sea slug). Our studies employ a variety of disease models and bear on numerous disorders, including blindness, deafness, neurodegenerative diseases, autism, infertility, and musculoskeletal disorders. The group provides interdisciplinary training in a collaborative environment for undergraduates, graduate students and postdoctoral fellows.
Aguilar, Claudio
It is well established that the processes of endocytosis and signaling are functionally linked. For example, endocytosis leads to receptor downregulation and shapes extracellular morphogen gradients.
Currently, our research is focused on the role played by the endocytic machinery in the regulation of signaling pathways relevant to developmental diseases such as Lowe, Bardet-Biedl and Senior-Løken syndromes.
In order to pursue our research goals we study protein-protein interactions by using biophysical, biochemical and genetic tools. We also investigate the physiological relevance of these interactions in live cells by combining siRNA-mediated knock-down, functional assays (e.g., cell migration), time-lapse microscopy and Fluorescence Resonance Energy Transfer.
Bartlett, Edward
The Central Auditory Processing Lab is interested in how neurons in the inferior colliculus, auditory thalamus, and auditory cortex represent features of sound in normal and impaired conditions such as those found in aging, dyslexia or autism. We are interested in the neural representations of sound at various levels – non-invasive sound-evoked potentials produced by large populations of neurons, in vivo discharge patterns to sound from a single neuron, single neuron intrinsic and synaptic currents produced by neurons involved in the generation of those patterns in vitro and measured by patch clamp recordings, and computational modeling of inferior colliculus and auditory thalamus neurons. In doing so, we are working towards bridging the gap between macroscopic level events that contribute to behavior with the integration of synaptic inputs at the cellular level.
Chang, Henry
Our research interest is to understand how membrane trafficking affects animal development. Specifically, we use Drosophila as the model organism to examine two processes: 1) The activation of Notch signaling by ligand internalization, and 2) The formation of the plasma membrane during sperm formation by the clathrin-mediated transport. Our main strategy is to identify and analyze genes participating in these events. By doing so, we can understand how these genes influence cell fate decision and cellular morphogenesis through membrane dynamics. Our experimental approaches include Drosophila genetics, molecular genetics, immunohistochemistry, fluorescent imaging, and electron microscopy.
Fekete, Donna
Our laboratory investigates inner ear embryology, with a long-term goal of using what we learn about developmental pathways to guide therapeutic strategies for treating deafness and balance disorders. We study genes that regulate inner ear morphogenesis, the specification of different sensory organs (auditory versus vestibular) or the polarization of hair cell bundles. Our studies use zebrafish, chicken and mice as model organisms. Our experimental approaches include molecular biology, embryology, virus-mediated gene transfer, antisense oligonucleotides, immunohistochemistry, in situ hybridization, tissue culture, confocal imaging and electron microscopy.
Hollenbeck, Peter
My laboratory is interested in long-distance transport within nerve cells. We are particularly interested in how these cells redistribute their mitochondria and how the process goes awry in neurodegenerative diseases. To observe and perturb nerve cells directly, we remove them from the nervous system of chick or Drosophila embryos and induce them to grow in vitro, where we can study their responses to specific molecular events using computer-enhanced light microscopy. We also measure intracellular events within nerve axons in vivo in Drosophila larvae using confocal microscopy. We have gained insight into how mitochondria are moved, how cell signaling directs them to the right part of the axon at the right time, and how their activity and replication are regulated across time and distance.
Konieczny, Stephen
Our laboratory is interested in defining the developmental and molecular mechanisms by which pancreas cell lineages are established and maintained. The pancreas is a complex organ consisting of three key cellular populations - islet cells that produce insulin, acinar cells that produce digestive enzymes and duct cells that transport the digestive enzymes to the intestine. Alterations in any one of these cell populations can lead to devastating disease states, including diabetes, pancreatitis and pancreatic cancer. Using a number of transgenic mouse models, molecular and cellular biology approaches, coupled with Affy microarrays, ChIPSeq, and Chip-on-Chip assays, we are identifying the key genes involved in establishing each cell lineage during normal embryogenesis and examining how alteration in gene expression patterns are instrumental to disease progression. Our long-term goals are to define the events required to generate each cell lineage and to develop new therapeutic strategies that can be exploited to successfully treat patients with altered cell lineages.
Leung, Yuk Fai
My laboratory is interested in gene regulatory network that controls eye development, with a long-term goal of using this blueprint to develop pharmacological approaches to regulate this process. This would ultimately facilitate development of novel therapeutic approaches for treating various blinding eye diseases. To this end, we particularly focus on retinal and retinal pigment epithelium development in the zebrafish model. We have being developing and utilizing whole genome expression analysis to identify transcription factors and signal transduction pathways that are associated with the development of these tissues. Then we apply a number of experimental approaches including gene perturbation, in situ hybridization, molecular biology, immunohistochemistry, various imaging methods (light, fluorescence, confocal, electron and live microscopy), statistics and computational modeling to characterize the roles of these molecules in eye development.
Mizukami, Yukiko
Developmental coordination between the cell cycle and cell differentiation
In multicellular organisms the cell cycle is coordinated with growth and differentiation during organogenesis. In plants this coordination is accomplished in a different way from that of animals due mainly to distinct functional, architectural, and developmental patterns or strategies. Research projects in our laboratory address the following questions to elucidate the mechanisms that link developmental signals to the cell cycle in plants:
1) How is the cell cycle regulated to maintain stem cell number of the shoot and root meristems during plant organogenesis?; 2) how is cell proliferation coordinated with cell and organ growth to define the intrinsic size of plant organs?; and 3) how is the switch from mitosis to endoreduplication linked to cell fate determination to give particular patterns in plant organs?
Otto, Kevin
The activities in my laboratory involve basic and applied
research utilizing neural engineering approaches to treat
neurological disorders. Research in our laboratory
continues along two complimentary directions:
Neuroprosthesis Development and Brain-Machine Interface
(BMI) Therapeutics. Neuroprostheses are devices designed
for communication with the nervous system to improve,
repair, or replace neural function and/or pathways. BMI
therapeutics include intervention strategies to improve the
performance of chronically implanted neuroprosthetic
devices. We develop and study: sensation induced by
electrical stimulation of neural tissue, enhanced electrical
interface materials, in situ and in vivo device-tissue
imaging, and device manipulation for stealth or drug
delivery.
Pak, William
In photoreceptors, a cascade of reactions convert light signals detected by rhodopsin into electrophysiological signals by opening the phototransducation channels, called TRP. Our laboratory has been interested in elucidating this process using Drosophila mutants. Our current focus is on the last step of this cascade, the nature of signals that open and regulate the TRP channels. The TRP channels are conserved throughout mammals, and the mechanism(s) of their excitation explored in Drosophila are expected provide insights into the operation of TRP channels in general. In addition, many genes encoding the proteins involved in the phototransduction cascade cause retinal degeneration, when mutated. One such gene of current interest is a Drosophila homolog of a causative gene for Usher syndrome, which is characterized by inherited deafness and retinal degeneration. We use bioinformatic, molecular, genetic, electrophysiological, biochemical and cell biological techniques.
Ready, Donald
Our laboratory seeks to understand mechanisms of the cytoskeleton and membrane transport in the development and maintenance of healthy photoreceptors. We apply genetic, molecular and cellular methods to Drosophila photoreceptors, a powerful model system, to conduct in vivo functional assays of genes and proteins essential for normal photoreceptor physiology and development. Recent work in the lab has focused on Rab11 and Myosin V in rhodopsin transport, calcium regulation of Myosin V motility, Arrestin translocation and the unfolded protein response.
Suter, Daniel
The functional nervous system is a complex network of an incredible number of specific neuronal connections. Our laboratory is interested in elucidating the molecular and cellular mechanisms of how neuronal growth cones guide axons to appropriate target cells during both development and regeneration. Specifically, we focus on the detection of guidance cues, downstream signaling and analysis of cytoskeletal dynamics. We use the large growth cones from Aplysia californica as our main model system, since they are excellent for quantitative analysis of fluorescent protein dynamics. Key techniques in our research include primary neuronal cell culture, advanced live cell imaging including Fluorescent Speckle Microscopy (FSM) and Fluorescence Resonance Energy Transfer (FRET), immunocytochemistry, molecular biology, biochemistry and biophysical approaches. We hope that our work will not only advance our understanding of neuronal development but also improve regeneration after injury and diseases.
Szeto, Daniel
(Cell, Molecular and Developmental Biology) Signaling pathway interaction to regulate the expression of genes that are responsible for the genesis of distinct cell-types during organogenesis in zebrafish.
Taparowsky, BJ
The AP-1 transcription factor complex controls cellular fate decisions critical to the development of all mammalian organisms. Since the core members of AP-1, the Fos and Jun proteins, are expressed ubiquitously by all cells, it is the participation of tissue-restricted proteins in the complex that allows AP-1 to tailor its function to a specialized cell type or to a specialized cellular response. Our laboratory studies the Batf family of AP-1 proteins which is expressed exclusively in hematopoietic cells. We are seeking to understand how these specialized AP-1 proteins function to control the growth and development of B and T lymphocytes. Utilizing transgenic and knock-out mice, we have defined specific roles for Batf-containing AP-1 complexes in the differentiation of T helper subsets and in coordinating the lymphocyte communication network required to generate a normal antibody response.
Bridges, C. David
(Biochemistry; physiology) Biochemistry and physiology of the visual process; evolution of vision; transport and utilization of vitamin A in the body; genes for retinoid-binding proteins, hereditary retinal degenerations.
Gardner, Stephanie
Instructor
Iten, Laurie
We focus on the production of digital media for teaching and research, especially in the area of developmental biology. We are also involved in the implementation of online educational technologies used in our classes, and other STEM disciplines.
Walls, Elwood
Continuing Lecturer