Department: Molecular & Cellular Physiology

Axel Brunger's goal is to understand the molecular mechanism of synaptic neurotransmission. He is particularly interested in the structure, function, and dynamics of key players in the synaptic vesicle fusion machinery. His lab is also working on the mechanism of action of clostridial neurotoxins that target this machinery. A molecular understanding of these complex protein machineries may ultimately lead to new therapeutics to treat human diseases.

We are interested in the structure, dynamics and function of eukaryotic transport proteins mediating ions and major nutrients crossing the membrane, the kinetics and regulation of transport processes, the catalytic mechanism of membrane embedded enzymes and the development of small molecule modulators based on the structure and function of membrane proteins.

Structural and functional studies of transmembrane receptor interactions with their ligands in systems relevant to human health and disease - primarily in immunity, infection, and neurobiology. We study these problems using protein engineering, structural, biochemical, and combinatorial biology approaches.

We study the molecular events that give rise to the sensation of touch and temperature in C. elegans. To do this, we use a combination of quantitative behavioral analysis, genetics, in vivo electrophysiology, and heterologous expression of ion channels. We also collaborate with Pruitt's group in Mechanical Engineering to develop and fabricate novel devices for the study of sensory transduction.

Most types of congenital and acquired hearing loss arise from damage to, or loss of hair cells, the sensory cells of the inner ear. Our work focuses on generating mouse and human inner ear cell types from stem cells and we are interested in signaling pathways that control hair cell (re-)generation in vitro and in vivo. In a second line of research, we are working on the identification and the molceular characterization of proteins that are important for hair cell function.

We are interested in the neuronal mechanisms that underlie synchronous oscillatory activity in the thalamus, cortex and the massively interconnected thalamocortical system. Such oscillations are related to cognitive processes, normal sleep activities and certain forms of epilepsy. Our approach is an analysis of the discrete components (cells, synapses, microcircuits) that make up thalamic and cortical circuits, and reconstitution of components into in silico computational networks.

Structure, function and physiology of adrenergic receptors.

We study molecular mechanisms of calcium signaling with a focus on store-operated CRAC channels and their essential roles in T cell development and function. Currently we aim to define the molecular mechanism for CRAC channel activation and the means by which calcium signal dynamics mediate specific activation of transcription factors and T-cell genes during development.

Our laboratory is focused on the development of adenocarcinomas, which are cancers of glandular tissues. Active projects are focused on pancreatic, esophageal, colon, and lung adenocarcinomas. Our work addresses the cause, diagnosis, and treatment of adenocarcinomas.

Our laboratory uses electrophysiological techniques to study the mechanisms of synaptic transmission and plasticity in the mammalian hippocampus. One of the main focuses in the lab is in the study of synaptic long-term potentiation (LTP). LTP is the persistent increase in synaptic strength that occurs after a period of heavy activity in a synaptic connection. It is the most widely studied and compelling model for mechanisms underlying memory formation in the mammalian central nervous system.

Molecular mechanisms of chloride channels & transporters studied by integration of structural and electrophysiological methods.

Clinical and molecular Imaging of cardiovascular disease, with a focus on coronary and vascular diseases, including atherosclerosis, aortic aneurysms, and vascular inflammation.

We study the primary cilium, a once-obscure cellular organelle recently "re-discovered" for its role in a number of signaling pathways. Defects in cilium biogenesis lead to a variety of hereditary disorders characterized by retinal degeneration, kidney cysts and obesity. Our goal is to characterize these disorders at the molecular and cellular levels to gain insight into the basic mechanisms of primary cilium biogenesis and to discover novel ciliary signaling pathways.

Our research objectives are to understand the cellular mechanisms involved in the development and maintenance of epithelial cell polarity. Polarized epithelial cells play fundamental roles in the ontogeny and function of a variety of tissues and organs.

Many adult organs tune their functional capacity to variable levels of physiologic demand. Adaptive organ resizing breaks the allometry of the body plan that was established during development, suggesting that it occurs through different mechanisms. Emerging evidence points to stem cells as key players in these mechanisms. We use the Drosophila midgut, a stem-cell based organ analogous to the vertebrate small intestine, as a simple model to uncover the rules that govern adaptive remodeling.

Reimer Lab interests A primary interest of our lab is to understand how nerve cells make and recycle neurotransmitters, the small molecules that they use to communicate with each other. In better defining these processes we hope to achieve our long-term goal of identifying novel sites for treatment of diseases such as epilepsy and Parkinson Disease. In our studies on neurotransmitter metabolism we have focused our efforts on transporters, a functional class of proteins that move neurotransmi..

The auditory sensory cell, the hair cell, detects mechanical stimulation at the atomic level and conveys information regarding frequency and intensity to the brain with high fidelity. Our interests are in identifying specializations associated with mechanotransduction and synaptic transmission leading to the amazing sensitivities of the auditory system. We are also interested in the developmental process, particularly in how development gives insight into repair and regenerative mechanisms.

Our laboratory investigates the cellular and molecular mechanisms of pain and its control by opioids. When chronic, pain is no longer an essential warning system critical to our survival, but a disease that severely affects the quality of life of many patients. We search to identity the neurons that participate in generating the sensation of pain and the molecular mechanisms that regulate neural activity in pain circuits to develop novel analgesic strategies against pathological pain.

Research in the Smith Laboratory addresses basic mechanisms and and disorders of brain function. Present efforts are focused on the development and application of new proteomic imaging methods to explore the circuit and molecular architectures of memory storage and retrieval in cerebral cortex.

Information transfer at synapses mediates information processing in brain, and is impaired in many brain diseases. Thomas Südhof is interested in how synapses are formed, how presynaptic terminals release neurotransmitters at synapses, and how synapses become dysfunctional in diseases such as autism or Alzheimer's disease. To address these questions, Südhof's laboratory employs approaches ranging from biophysical studies to the electrophysiological and behavioral analyses of mutant mice.

We study synaptic communication between brain cells with the goal of understanding neuronal computations and memory mechanisms. Main areas of focus include: presynaptic calcium channels, mechanisms of vesicular fusion and recycling. Modulation of synaptic strength through changes in postsynaptic receptors and dendritic morphology. Signaling that links synaptic activity to nuclear transcription and local protein translation. Techniques include imaging, electrophysiology, molecular biology.

Our laboratory studies molecular interactions that underlie the establishment and maintenance of cell and tissue structure. Our specific areas of interest are the architecture and dynamics of intercellular adhesion junctions, the molecular basis of cell polarity, and the Wnt signaling pathway. We also have a long-standing interest in carbohydrate-based cellular recognition and adhesion.