Robert E. Marc - Abstract and Bio
Abstract
Molecular Phenotype Atlases: Motivation, Challenges, and Workflow
Robert E. Marc, Ph.D.
Calvin & JeNeal Hatch Professor of Ophthalmology
Director of Research
John A. Moran Eye Center,
University of Utah
By building anatomic atlases of molecular probes, morphologists have attempted to mimic the power of large-scale sampling and mining enjoyed by molecular biologists. The challenges are basic. What probe libraries can or should be used and what should they target: small molecules, proteins, mRNA? What resolution, coverage, statistical power and throughput can be achieved? What analytic tools should be used? Ultimately, how do we standardize these tools for classical studies of non-stationary biology: development, disease, stress, adaptation, evolution, nutrition, and other biologic rhythms?
As an example, one motivation for atlas building involves mapping rich but disembodied metabolomic (http://hmdb.ca) and pathway data (http://www.genome.jp/kegg) onto tissue atlases at cellular resolution. Why? Put simply, advanced organisms partition physiologic operations and metabolic chemistries into topologically complex mixtures of cell classes (metabolons) in tissues. Visualization of small molecule probe sets as molecular signature maps, along with quantitative imaging and cluster analysis unmasks high metabolic diversity across and metabolic precision within constituent cell classes of various metabolons. Metabolon topologies emerge as strongly gridded cell mixtures (neuroglial and muscle systems), discrete serial modules (pulmonary and renal assemblies), and large-scale coupled gradient systems (liver). Importantly, classification tools and signature visualization give a powerful way of tracking cell states. The next challenges involve harmonizing small molecular and protein phenotype maps.
Finally, new developments in probe technologies and visualization promise simpler platforms and less expensive workflows. The largest remaining challenges are computational. Currently, tools for creating, analyzing, exploring and managing multichannel imagery are an idiosyncratic melange of applications, transforms and platforms. Leveraging large-scale atlas data would be substantially accelerated by the emergence of standardized, integrated image processing/classification/management tools that will allow real users (rather than mavens) to manage workflow.
Bio: Robert E. Marc
Robert E. Marc (b. 1949) holds the Calvin and JeNeal Hatch Presidential Chair in Ophthalmology at the University of Utah and is Director of Research for the John A. Moran Eye Center. He obtained a B.Sc. with Honors at the University of Texas / El Paso (1971) and a PhD in Neuroscience at University of Texas / Houston (1975) where he produced the first chromatic cone map of the retina. During postdoctoral work with W.K. Stell at UCLA he began the process of mapping retinal pathways using cell-specific markers and electron microscopy. He joined the University of Texas / Houston as an assistant professor (1978) and remained there until 1993, when he joined the Moran Eye Center at the University of Utah. Since then, work in the Marc laboratory led to the development of computational molecular phenotyping, new functional probes of neuronal excitation, and discovery of extreme retinal remodeling in retinal degenerations. His research has been funded by the NIH since 1978.
