Biomedical subjects

Robert E Ward

Publications and source records attributed to Robert E Ward.

4 recordsLinked to original sources

PubMed2004

Understanding milk's bioactive components: a goal for the genomics toolbox.

The challenges to food research are to propel foods beyond the successes of safety, convenience, and inclusion of all the essential nutrients, and to build the knowledge of genetics, metabolism, and biomolecules necessary for developing foods that deliver optimal health to each individual. How then can scientific and biological principles be developed to assemble this knowledge? The evolutionary success of milk has afforded compelling examples of a food material designed by selective pressure to provide optimal health to healthy mammalian offspring. Milk contains components that are more than assembled essential amino acids and that provide biological activities that improve the competitive success of offspring who consume them. Many of these molecules are proteins that protect individuals from exogenous stresses, toxins, and pathogens; encourage optimal growth, development, and adaptation to a chosen environment; and promote metabolic regulation for physical and intellectual performance. These structures and their actions are the basis of nutritional benefits that were not recognized when freedom from amino acid deficiency was the sole criterion of protein quality. The rapidly expanding tools of biotechnology are enabling a new perception of ingested proteins, how they are regulated, and how they achieve their specific functions. Genomes and their analyses are revealing the molecular details of their remarkable structural complexity and design. Milk proteins, either exclusively synthesized in the mammary gland during lactation or transported from plasma and concentrated in the mammary gland, have been largely co-opted from other functions. Establishing the evolutionary lineage of orthologous milk proteins, including the physiological process from which they were recruited, will lead to identification of their bioactivity. While most emphasis has been placed on the genes per se, our approaches implicate the regulatory regions of the genome as additional targets of milk's biological information content. Understanding the structures is guiding scientists to new food ingredients. Understanding structures and regulation will guide scientists to new benefits and ultimately to the knowledge to build a new generation of delicious foods that genuinely deliver on the promise of safety and maintenance of optimal health.

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PubMed2003

GFP in living animals reveals dynamic developmental responses to ecdysone during Drosophila metamorphosis.

Studies of Drosophila metamorphosis have been hampered by our inability to visualize many of the remarkable changes that occur within the puparium. To circumvent this problem, we have expressed GFP in specific tissues of living prepupae and pupae and compiled images of these animals into time-lapse movies. These studies reveal, for the first time, the dynamics and coordination of morphogenetic movements that could only be inferred from earlier studies of dissected staged animals. We also identify responses that have not been described previously. These include an unexpected variation in some wild-type animals, where one of the first pairs of legs elongates in the wrong position relative to the second pair of legs and then relocates to its appropriate location. At later stages, the antennal imaginal discs migrate from a lateral position in the head to their final location at the anterior end, as leg and mouth structures are refined and the wings begin to fold. The larval salivary glands translocate toward the dorsal aspect of the animal and undergo massive cell death following head eversion, in synchrony with death of the abdominal muscles. These death responses fail to occur in rbp(5) mutants of the Broad-Complex (BR-C), and imaginal disc elongation and eversion is abolished in br(5) mutants of the BR-C. Leg malformations associated with the crol(3) mutation can be seen to arise from defects in imaginal disc morphogenesis during prepupal stages. This approach provides a new tool for characterizing the dynamic morphological changes that occur during metamorphosis in both wild-type and mutant animals.

Animals↗

PubMed2003

Genetic modifier screens in Drosophila demonstrate a role for Rho1 signaling in ecdysone-triggered imaginal disc morphogenesis.

Drosophila adult leg development provides an ideal model system for characterizing the molecular mechanisms of hormone-triggered morphogenesis. A pulse of the steroid hormone ecdysone at the onset of metamorphosis triggers the rapid transformation of a flat leg imaginal disc into an immature adult leg, largely through coordinated changes in cell shape. In an effort to identify links between the ecdysone signal and the cytoskeletal changes required for leg morphogenesis, we performed two large-scale genetic screens for dominant enhancers of the malformed leg phenotype associated with a mutation in the ecdysone-inducible broad early gene (br1). From a screen of >750 independent deficiency and candidate mutation stocks, we identified 17 loci on the autosomes that interact strongly with br1. In a complementary screen of approximately 112,000 F1 progeny of EMS-treated br1 animals, we recovered 26 mutations that enhance the br1 leg phenotype [E(br) mutations]. Rho1, stubbloid, blistered (DSRF), and cytoplasmic Tropomyosin were identified from these screens as br1-interacting genes. Our findings suggest that ecdysone exerts its effects on leg morphogenesis through a Rho1 signaling cascade, a proposal that is supported by genetic interaction studies between the E(br) mutations and mutations in the Rho1 signaling pathway. In addition, several E(br) mutations produce unexpected defects in midembryonic morphogenetic movements. Coupled with recent evidence implicating ecdysone signaling in these embryonic morphogenetic events, our results suggest that a common ecdysone-dependent, Rho1-mediated regulatory pathway controls morphogenesis during the two major transitions in the life cycle, embryogenesis and metamorphosis.

Animals↗

PubMed2002

Bioactive components in milk.

Milk is the only biomaterial that evolved under the Darwinian selective pressure to nourish growing mammals. The purpose of this article is to review the scientific research that is using new techniques of integrating biological sequence, structure and function, to understand the innovative biology underlying the products of that evolutionary pressure. As it emerges that milk is actively communicating between the maternal mammary epithelia and the infant's gastrointestinal system, actively directing and educating the immune, metabolic and microflora systems within the infant, enhancing nutrient absorption and delivery, and conferring multiple means of protection, nutritionists are gaining a host of new molecular targets towards which to build scientific strategies for future foods and clinical applications. As new components and functions are being discovered in milk by using traditional methods and modern genomic tools, the complexities of demonstrating, and particularly in humans, the functional mechanisms behind milk's newly observed physiological benefits are becoming the next challenge of this rapidly growing field.

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