Faculty & Laboratories

  Left to right: Michael Rosbash, Sacha Nelson, Leslie Griffith, Piali Sengupta, Paul Garrity, Susan Birren, and Gina Turrigiano. Not shown: Suzanne Paradis.  

A goal of modern neuroscience is to understand how genes and their expression interact with neuronal network function to produce complex behaviors. A unique strength of the NCBG is its diverse faculty, who use a broad range of approaches in multiple model systems. Three NCBG faculty, Susan Birren, Sacha Nelson, Suzanne Paradis and Gina Turrigiano, work on mammals - principally mice.

Susan Birren is interested in how embryonic precursor cells respond to local environmental cues during the development of the mammalian nervous system. She has focused on the restriction of neural precursor cells to specific neuronal lineages and the development and function of synaptic connections. Birren has a special interest in neurotrophins as well as neurotrophin receptors and their role in lineage restriction as well as plasticity. She is also collaborating with Sengupta (see below) and exploiting the complementary strengths of the mouse and C. elegans systems to study mutations in the Arx system, a conserved genetic pathway that underlies several forms of human mental retardation and autism.

Sacha Nelson is interested in the mammalian neocortex, neuronal anatomy, circuitry and function. This brain region has an awesome complexity of neuronal morphologies, and Nelson has recently used microarray approaches to help define subtypes and even suggest functional specialization. In addition, Nelson shares an interest with Gina Turrigiano in Rett's Syndrome, a major genetic cause of mental retardation. It is known that this disease is caused by the loss of a transcriptional repressor, and they study the physiological consequences in a mouse model of Rett's Syndrome. Nelson and Turrigiano also share an interest in cortical circuitry, physiology and mechanisms of synaptic plasticity.

Suzanne Paradis focuses on the complex circuitry of the mammalian brain that enables the execution of fundamental cognitive processes such as learning, speech, and memory. Neural circuits are assembled via specialized sites of cell-cell contact and communication between neurons termed synapses. Aberrant synapse development can have pathological consequences for circuit function as demonstrated by the manifestation of devastating neurological impairments, including epilepsy and autism spectrum disorders. The aim of our research is to define the molecular program that underlies both excitatory and inhibitory synapse development with the goal of contributing to a greater understanding of neural circuit formation and function.

Gina Turrigiano has an additional focus on the role of early environmental influences on the development of cortical circuitry and the plasticity mechanisms that underlie optimal cortical development. Her lab is particularly focused on homeostatic scaling, a phenomenon she proposed to deal with the daunting problem of simultaneously maintaining flexibility and stability of neuronal circuits. Birren, Nelson and Turrigiano are also working on the sleep problem from several directions: circuitry, physiology anatomy, and molecular biology, e.g., what happens to gene expression in response to sleep deprivation.

Four NCBG faculty, Paul Garrity, Leslie Griffith, Michael Rosbash and Piali Sengupta exploit invertebrate model systems, either the fruit fly Drosophila or the worm C. elegans. Both models are widely used, because many genes and processes central to the study of brain and behavior are conserved between humans and these organisms; their facile genetics and low cost are also appealing.

Paul Garrity studies neuronal morphogenesis and circuit formation in Drosophila. He is also interested in the molecular basis of behavior, focusing on the molecules and circuits controlling thermosensation and thermotaxis. The molecular pathways that mediate thermosensory behavior in flies are related to the pathways that mediate temperature sensation, pain and inflammation in mammals, suggesting that a deeper understanding of fly thermosensory behavior will lead to insights of significance for human health.

Piali Sengupta shares similar interests and uses C. elegans to study how sensory neurons, thermosensory as well as olfactory, recognize environmental cues and how they elicit appropriate changes in development and behavior. Developmental question include how sensory complexity is generated, and behavioral questions include how plasticity is regulated, which occurs in part at the level of olfactory receptor gene expression. More recent objects of study include the neural and molecular correlates of thermosensation and thermal memory.

Leslie Griffith focuses on regulation of the neuronal circuits underlying learning and memory using Drosophila. Much of the work is centered around the role of calcium/calmodulin-dependent proteins kinase II (CaMKII), an enzyme that is central to memory formation in both invertebrates and mammals. Griffith is also interested in the circuitry that underlies sleep in flies. Although sleep was once considered to be an exclusively vertebrate behavior, it is now widely believed that invertebrates like Drosophila also sleep, and many critical features of human sleep can be studied in flies.

Michael Rosbash is also interested in fly sleep, which is an outgrowth of his interest in circadian rhythms. The circadian clock regulates a daily sleep cycle (alternating periods of alertness and sleep), in flies as well as in humans. This cycle is aberrant in mutant fly strains as well as in certain human sleep disorders. Most if not all of the key molecules that function to regulate circadian timekeeping are identical between flies and humans, making this system essential for understanding this problem.

 

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