IGERT Funded Research

It is impossible to describe all of the opportunities for research at Brandeis that will be available to the IGERT trainees. Below we have defined six levels of organization, and describe examples of research at each level of organization open to IGERT trainees.

	Research Description	Examples
1)	Understanding the structure, function, and dynamics of single molecules. A major goal of this project is to understand the structure and function of single protein molecules. Our faculty have long used classical tools for the investigation of single protein structure, function, and dynamics including single channel studies (Chris Miller), x-ray crystallography and structural biology (Greg Petsko, Dagmar Ringe, Carolyn Cohen) and NMR (Dorothee Kern, Thomas Pochapsky). These endeavors continue, and require students with strong quantitative skills. Additionally, new highly collaborative projects will provide exciting research topics for IGERT trainees interested in working at this level of analysis.	Microfluidics for Protein Crystallization Roles of structure and motion in enzyme function
2)	Understanding macromolecular assemblies and protein machines. In cells, proteins do not function alone, but instead combine in multiprotein assemblies that are the biological machines that carry out most of the important functions in cells. Understanding how these machines work requires both understanding the structure of the individual protein constituents and understanding how they are put together and function in assemblies to carry out complex tasks in the cell.	Structural Dynamics of Macromolecular Machines Chromosome Dynamics in Yeast
3)	Developing a new biochemistry demanded by understanding the implications of restricted space in cells. Most of what we know about the chemistry of biological macromolecules comes from conventional studies done in test tubes with homogenous solutions and reactions run at equilibrium. However, it is now clear that in many cells, important reactions occur in very restricted spaces, so that the insights from equilibrium, large-volume biochemistry, while a starting point, may not provide adequate insight into how signals are processed in real cells. Moveover, many protein machines exist that bring together reaction products, creating defined local environments in which reactions take place. Therefore, it is necessary to develop both theoretical and experimental tools to understand biochemistry in small spaces.	Synaptic Switches and Non-equilibrium Biochemistry
4)	Understanding gene networks and expression patterns that determine cell identity. One of the fundamental problems in biology is understanding how each cell acquires its specific identity in development through a sequence of events involving the interaction of the cell with its environment and transcriptional regulation. For example, the Sengupta lab is interested in understanding how the diverse and unique functional identities of individual sensory neurons are specified. Using genetic and genomic experimental approaches, they have described genetic networks and linear cascades of transcription factors that act to specify the functional as well as morphological characteristics of individual sensory neuron subtypes of C. elegans. Current work is aimed at understanding how these transcriptional factor codes are interpreted and integrated at target gene promoters, and at identifying additional components of these networks. One of our collaborative research goals will be to implement formal theoretical models that capture these interactions and make predictions from them.	Cellular Genomics of the Nervous System
5)	Understanding how network function arises from component properties. The ultimate goal of much systems biology is to explain how the behavior of an entire system arises from the properties and interactions of its constituent parts. In practice today, to fully understand how system properties depend on the properties of their underlying components requires the use of computational models to explore the consequences of alterations in the concentrations, properties or connections among system compenents. Therefore, it is crucial that students interested in integration, at the level of signal transduction pathways, transcription factor networks, or neural circuits obtain experience with modeling techniques. In all of the projects outlined below, computational and experimental approaches are required, and will be used.	Biological Oscillators Biological Integrators Organismal, organ, circuit, cellular stability despite molecular turnover.
6)	Understanding higher brain function from basic cellular processes. The vertebrate brain stands out as one of the most complex systems in biology. As such, understanding human cognitive function in terms of its underlying mechanisims represents one of the most ambitious goals of biological study. If one wishes to eventually understand human cognitive function, it is important to develop detailed and quantitative measures of human performance, and attempt to express these in crisp quantitative formulations that provide that define "what it is we need to explain", as we go into more mechanistic studies. At Brandeis there are a number of groups (Robert Sekuler, Arthur Wingfield, József Fiser, James Lackner, Paul DiZio) that do detailed quantitative analyses of aspects of human cognitive function that inform work that our systems neuroscientists do on behaving animals. Moreover, most of what we think we know about sensory and motor systems in higher vertebrates come from studies on anesthesized animals, and one of the goals of our systems level scientists is to understand how sensory processing occurs in behaving animals.	Vision Multielectrode arrays to record neural signals from behaving animals