he 11th annual symposium is hosted at the University of San Diego for the first time.

Marilyn H. Perrin, Ph.D., Staff Scientist, The Salk Institute

Marilyn Perrin earned her B.S. in Chemistry at UCLA and her Ph.D. in Chemistry in 1972 at Harvard University where she worked with Prof. Martin Gouterman on vibronic borrowing in the electronic spectra of polyenes and porphyrins. In 1975 she changed her area of research from quantum chemistry to neuroendocrinology at the Salk Institute by joining the laboratory of Prof. Roger Guillemin, who shared the 1978 Nobel Prize for the discovery of hypothalamic releasing factors. Marilyn has continued at the Salk Institute in the Peptide Biology Laboratory of Prof. Wylie Vale. Her research, focusing on hypothalamic releasing factor receptors, resulted in the cloning of the first receptor for corticotropin releasing factor in l993, followed in 2004 by the first three-dimensional NMR structure of the receptor's major binding domain.

Molecules of stress: Peptides and receptors—from sequence to three-dimensional structure.
The 40-amino acid peptide corticotropin releasing factor (CRF) plays a key role in integrating the autonomic, endocrine and behavioral responses to stress. The CRF family of ligands also includes the related peptides urocortin 1,2, and 3. These peptides display diverse effects on the brain and pituitary as well as on the cardiovascular, gastrointestinal, reproductive and immune systems. The ligands initiate their cellular actions by binding and activating heptahelical membrane proteins, which are G-protein coupled receptors. The CRF receptor family also includes receptors for growth hormone releasing hormone, parathyroid hormone, calcitonin and glucagon. The first extracellular domains (ECD1s) of the receptors constitute major peptide recognition sites. Our three-dimensional NMR structure of the ECD1 of a CRF receptor (1) identifies its structural fold as a Sushi domain, in which a cluster of amino acids serves as a peptide-binding interface. Based on the conservation of key amino acids in the ECD1s of the other receptors in the family, we propose that the three-dimensional structure of ECD1 of the CRF receptor serves as a model for the structure of the ECD1 of those receptors and, further, provides insight into the mechanism of activation of this family of receptors.

(1) Grace, C.R.R., et al., "NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G-protein coupled receptor." Proc. Natl. Acad. Sci. USA101, 12836-12841, (2004).

 

Professor Hsieh-Wilson is Assistant Professor of Chemistry at the California Institute of Technology and Investigator of the Howard Hughes Medical Institute.

She received her B.S. degree in chemistry from Yale University in 1990 and her Ph.D. degree in chemistry from the University of California at Berkeley, where she worked with Professor Peter G. Schultz. From 1996 to 2000, she was a postdoctoral fellow at The Rockefeller University with Professor and Nobel Laureate Paul Greengard. In 2000, she joined the faculty at the California Institute of Technology. Her honors include the Research Corporation Research Innovation Award, NSF CAREER Award, and Eli Lilly Award in Biological Chemistry. Professor Hsieh-Wilson has also been named a Beckman Young Investigator and an Alfred P. Sloan Fellow. In 2005, she was appointed an Investigator of the Howard Hughes Medical Institute.

Decoding Structure-Activity Relationships of Carbohydrates in the Brain
Our research integrates organic chemistry with neurobiology to explore the molecular basis of neuronal communication and information storage in the brain. In particular, we are interested in understanding how specific carbohydrate structures contribute to the formation and strengthening of neuronal connections. Chondroitin sulfate glycosaminoglycans are sulfated polysaccharides attached to extracellular proteins that have been implicated in brain development, cell division, and spinal cord injury. We have developed chemical strategies that permit the first direct investigations into the structure-activity relationships of chondroitin sulfate and define a particular sulfated tetrasaccharide as a minimal structural motif endowed with neuronal growth-promoting activity. In the intracellular context, the covalent attachment of O-linked-b-N-acetylglucosamine (O-GlcNAc) to protein side chains is a dynamic modification that shares features with protein phosphorylation. The development of new technologies to study the modification in cells as well as functional implications of O-GlcNAc for diabetes and information storage will be discussed.

 

Jilly Evans, Ph.D, Vice President Amira Pharmaceuticals

Jilly Evans is a native New Zealander educated in rural New Zealand schools and then at Auckland University in Cell Biology and Biochemistry. She received her PhD in Biochemistry from the University of British Columbia in 1978 working with Michael Smith who won the Nobel Prize in 1993 for the development of site-specific mutagenesis. She carried our post doctoral research in the department of Biochemistry at McGill University before joining Merck Frosst Canada in 1983 to work on therapies in the leukotriene pathway. She took part in the discovery of 5-lipoxygenase-activating protein (FLAP), a target for leukotriene synthesis inhibitors, and the development of the CysLT1 receptor antagonist, Singulair. She enjoyed her 4 years as an adjunct professor in the Department of Biochemistry teaching first year medical students their lipid biochemistry-particularly the section on leukotrienes and prostaglandins. Jilly was the lead biochemist in the team that discovered the COX-2 inhibitor Vioxx. She led the Merck orphan GPCR ligand identification group for 5 years during which time they solved the identity of ligands for several orphan GPCRs including the motilin receptor and the CysLT1 and CysLT2 receptors. In mid 2005 Jilly left Merck after 21 years to be a founding member of a start up biopharmaceutical company in San Diego. Amira Pharmaceuticals to lead the biology in the development of therapeutics for inflammatory driven diseases.

Therapeutic Opportunities in the Leukotriene Pathway
Leukotrienes are potent inflammatory and constrictive molecules involved in respiratory and cardiovascular diseases. Successful leukotriene inhibitor (5-lipoxygenase) and antagonist (CysLT1 receptor) therapies have been marketed for asthma and allergic rhinitis. Recent human genetic linkage of haplotypes in leukotriene pathway genes to myocardial infarction and stroke have reignited pharmaceutical interest in the development of novel leukotriene inhibitors and antagonists. The chemistry and biology of the development of therapies targeting the leukotriene pathway proteins will be outlined. In addition, a new paradigm for patient selection by genotype and phenotype will be discussed.

 

Rhonda Morgan earned a BS in 1995 at Caltech in Electrical Engineering emphasizing remote sensing and radio interferometry. In 2001 she received her PhD in Optical Sciences from the University of Arizona. Her honors include a NASA GSRP Fellowship, the Optical Society of America’s New Focus Student Award and a Michelson Post-doc Fellowship. Rhonda began her research career in high school at Sandia National Laboratories where she developed electromagnetic coil guns for space launch and, during college summers, designed and tested binary optic wavefront sensors for combining high power laser beams. As an undergraduate, she worked part time at JPL on laser communications and on metrology for separated spacecraft interferometers. Her graduate research demonstrated a technique for achromatic nulling interferometry for planet detection. Her recent work at JPL has encompassed separated space craft interferometers, the Terrestrial Planet Finder mission, membrane space telescopes for the mid-infrared, Shack-Hartmann sensing with extended scenes, and wavefront sensing and control for lightweight deformable mirrors. She is currently working feverishly on a deformable mirror telescope scheduled for launch in a year and a half.

Rhonda Morgan still remembers her first view through a telescope was of the rings of Saturn during the year of Halley’s Comet. It was love at first sight. She has pursued many astronomical observing opportunities and considers the top three to be Jupiter’s red storm through a 60-inch telescope, Comet Hale-Bopp, and the Leonid meteor shower the night before her dissertation defense. Space exploration and science education have been lifelong passions. Her first science fair project, in the third grade, explored pinhole cameras. Her first published paper was on science education. She started a space science club at her high school and spoke on the radio about light pollution. She gave science demonstration talks throughout college and graduate school. At JPL, she participates in the Caltech undergraduate mentoring program for women. She also enjoys playing the harp, swing dancing, calligraphy, and filmmaking.

A History of Orion Through the Eyes of Telescopes and the Future Prospects for Detecting Life
Kant and Laplace theorized solar system formation as a rotating disk of matter as early as 1796 and yet these disks were not directly imaged until 1996. Planets around other stars were not discovered until 1995, and the known population has exploded to 170, including 17 multi-planet systems. Evidence is quickly mounting that dust disks are abundant, planets may be abundant, solar systems do exist, earth-like planets are likely to exist, and life on other planets may exist.

What are the future prospects for detecting life? A technology roadmap has been developed, but how soon may we be able to achieve this? What are the technological hurdles we must surmount? What are the current advances and challenges in space telescopes? How do the observing instruments limit and propel the scientific discovery?

Come on this journey of the evolution of telescopes, using the Orion nebula as a visual example, and explore the plans for the future of telescopes, especially space-based telescopes designed to discover terrestrial planets and to detect life-markers.

Rhonda Morgan is a Member of the Technical Staff at the California Institute of Technology’s Jet Propulsion Laboratory, managed under contract to NASA.