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Lewis-Sigler Institute for Integrative Genomics

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Amy Caudy , Ph.D. (Lewis-Sigler Fellow) studies the function and replication of mitochondria. Using genetic approaches in yeast and mammalian cell culture, she plans to clarify the relationship between mitochondrial function and cell growth. While oxidative phosphorylation is dispensable in some types of cells, an intact mitochondrial compartment is essential for cell survival. A major focus is the development of biochemical approaches to identify functional protein complexes and to validate the predictions made by genetic experiments.
Jeremy L. England , Ph.D. (Lewis-Sigler Theory Fellow) applies the theoretical tools of equilibrium and non-equilibrium statistical physics to understanding the different ways structure can arise in living systems. Whether on the scale of a self-assembling macromolecule or that of a developing embryo, he is interested in how it is that reliable, functional architecture manifests in systems whose underlying dynamics are driven by random fluctuations.
Matthias Kaschube , Ph.D. (Lewis-Sigler Theory Fellow) is interested in how structured collective behavior emerges in biological systems, in particular how these remarkable phenomena arise from the properties and interactions of microscopic individual components. In the mammalian cortex, he studies the formation of neural circuits underlying selective responses of neurons to visual stimuli. In Drosophila embryos, he investigates cell shape changes and the intercellular interactions involved in the coordinated collective cell movement during ventral furrow gastrulation. His aim is to characterize biological systems with quantitative precision and to develop mathematical descriptions that capture the essence of these observed phenomena.
Megan McClean , Ph.D. (Lewis-Sigler Fellow) studies the design principles underlying the signal processing capabilities of biological networks. Cellular signaling networks transmit information about environmental stimuli to the interior of the cell where appropriate cellular responses take place. How these networks process their input dictates cellular behavior and fitness. She is interested in how signaling pathways and transcriptional networks are designed to appropriately filter input and set thresholds so that cells respond optimally to changes in their environment. She is also interested in understanding how these networks are adapted and fine-tuned throughout development (short timescale) or evolution (long timescale). Her lab takes an experimental approach combining microfluidics with microscopy to monitor the responses of signaling pathways to complex stimuli.
Marcus Noyes , Ph.D. (Lewis-Sigler Fellow) focuses on the use of traditional methods as well as the development of new techniques to provide a better understanding of how proteins and DNA interact with one another. By doing so he hopes to provide a greater understanding of the complex networks that control what genes are expressed in any given cell type under any given condition. In addition, he uses these same tools to engineer novel DNA-binding proteins to specify desired sequences of DNA. These artificial factors can be used to target activators or repressors to site-specifically control gene expression as well as make targeted genomic modifications for therapeutic and experimental applications.
Ethan Perlstein , Ph.D. (Lewis-Sigler Fellow) introduces small molecules, including therapeutic drugs, into simple model organisms like the budding yeast Saccharomyces cerevisiae, and studies the impact on their physiology, thereby revealing evolutionarily conserved aspects of human diseases (e.g., schizophrenia and diabetes). More specifically, using genomic and chemical-screening technologies, he assesses effects of genetic variation, both natural and engineered, on the complex physiological responses of yeast cells to therapeutic drugs, in order (1) to discern the mechanism of action of these drugs on yeast, and, (2) to translate that insight to mammalian disease models. More generally, his methodology enables a comprehensive study of the evolution of complex traits.
Eva-Maria Schoetz , Ph.D. (Lewis-Sigler Fellow) studies generic physical mechanisms that play a role for cell movements and tissue formation during embryogenesis and regeneration. Cell movements and tissue flow constitute a beautiful problem of bridging scales: On the microscopic scale, cells are expressing particular genes which determine their identities and also their fate. These molecular determinants then lead to the macroscopic phenomena of cell movements and tissue arrangements, for which one needs a continuum description in terms of active fluids. A complete coarse graining, however, is not possible, since the number of cells is fairly small. Thus, a characterization of both mesoscopic (individual cell motion) and macroscopic (flow) properties is required for a full description. In my group, we want to address both scales experimentally by 3D and 4D fluorescent light microscopy and image analysis, laser ablation, application of external magnetic and electric fields, microrheology and whole tissue rheology. Experimental systems include zebrafish embryos and planaria.









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