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Large-scale DNA sequencing of a variety of organisms has led to a detailed annotation of genes and regulatory elements dispersed throughout their genomes. These genetic elements are embedded in the DNA fibers packaged in the nucleus. Such genome packaging is not simply accomplished by condensing genetic material, but distant genomic loci are also non-randomly localized in the nucleus.
It is becoming clear that the three-dimensional (3D) structure of the genome is linked to numerous nuclear processes, including transcription. Moreover, it is known that the eukaryotic genome is disorganized in certain human diseases, including various cancers, but it remains unclear how the disorganization of the 3D genome structure influences pathological processes.
We have been characterizing genome-organizing mechanisms in the model organism fission yeast and also exploring the role of genome disorganization in cancer. Our laboratory employs latest genomic assays, fluorescent microscopy, molecular biology, and biochemical approaches, in addition to exploiting the power of yeast genetics. By uncovering the molecular mechanisms governing 3D genome structure, the Noma laboratory seeks to establish a clear mechanistic framework for understanding the molecular underpinnings for human cancers related to genome disorganization.
We recently pioneered an innovative genomic methodology that combines the molecular biology procedure called chromosome conformation capture (3C) and massively parallel DNA sequencing. Using this genomic approach we have modeled the 3D structure of the entire fission yeast genome during interphase.
The microscope in the image belonged to William E. Horner, M.D., a collaborator with Caspar Wistar, M.D., in the early 1800s.
Dr. Horner, a lecturer at the University of Pennsylvania, was a pioneer of the use of microscopes in anatomical and medical research. He authored Special Anatomy and Histology, a seminal text on the subject.