Dr. Kramer is a biochemist internationally recognized for his comprehensive research program investigating insect cuticle structure, chitin metabolism, tanning chemistry, neuropeptides, molting, digestion, and the use of biopesticides and insect growth regulators for insect pest control. Results of his research have had major impact in insect molecular science and also preharvest and postharvest insect pest management programs including the development of insect growth regulators, biopesticides, transgenic plants and biological control agents by the agricultural biotechnology industry. Until his retirement in 2003, he was a research chemist at the USDA-ARS Center for Grain and Animal Health Research (CGAHR) and Adjunct Professor of Biochemistry at Kansas State University (KSU) in Manhattan, Kansas. Presently, he is a collaborator at CGAHR and Adjunct Professor Emeritus of Biochemistry at KSU.
1. Insect cuticle structure and tanning metabolism. The insect exoskeleton or cuticle serves many functions including protection, locomotion, respiration and communication, and therefore must have very diverse mechanical and chemical properties to provide for optimization of each function. Kramer and his collaborators have elucidated many of the metabolic reactions responsible for the stabilization (sclerotization and biomineralization) and pigmentation of cuticular exoskeletons, including the quinone-mediated cross-linking of structural proteins. They characterized several regulatory enzymes and reaction mechanisms critical for cuticle tanning, and also delineated several of the hormonal mechanisms that help to regulate cuticle morphogenesis and recycling. Kramer's research group was the first to apply the noninvasive spectroscopic technique of solid state nuclear magnetic resonance for the compositional and structural analyses of many types of insect sclerotized structures including cuticles, egg cases, and cocoons. The results of these studies provided new knowledge about insect support structures and their mechanisms of stabilization and regulation, and also yielded new insights into how insects have evolved extracellular components with different properties, which contributed to their great diversity and success in nature. The information also is useful to scientists involved in the development of biotechnological methods of insect pest control, which are designed to disrupt insect cuticle physiology.
2. Insect chitin metabolism. Chitin is the major structural polysaccharide found in the exoskeleton and gut lining of insects. Kramer and his collaborators determined the properties of several chitinolytic enzymes, elucidated the mechanism and hormonal regulation of cuticular and gut chitin digestion by these enzymes, cloned several chitin synthesizing and chitinolytic enzyme genes, and transformed several plants and an entomopathogen with an insect chitinase gene. This effort has not only yielded knowledge about molting and digestive biochemistry and physiology but also demonstrated that expression of an insect chitinase gene in transgenic plants and microbial entomopathogens enhances host plant resistance and increases the efficacy of biological control agents for insect and fungal pests. A patent for the use of insect chitinase as a biocide was issued in 1999 and development of the this transgene as a defense gene in wheat, corn, rice, sorghum and other plants is ongoing. Kramer's research group also showed that chitin inhibitors such as diflubenzuron and other types of insect growth regulators are effective as stored product protectants against insect pests. These efforts helped to establish that chitinolytic enzymes and insect growth regulators that inhibit cuticle and gut physiology can be used to exploit chitin metabolism for insect control purposes.
3. Development of Bacillus thuringiensis toxins as biopesticides in transgenic plants. Proteinaceous insecticides from the bacterium Bacillus thuringiensis (Bt) disrupt insect gut physiology and are now being expressed in transgenic plants for insect control. Kramer was part of a team that determined the chemical and functional properties of the protoxins from this entomocidal bacterium and also helped to characterize the midgut proteinases from Bt-susceptible and Bt-resistant strains of insects, which process the protoxins to toxins. The team discovered a novel mechanism of insect resistance to Bt, which involves a change in gut proteinase activity and results in a diminished ability of the resistant insects to activate the protoxins. These studies provided pioneering knowledge about the structure, toxicological action, and insect resistance mechanisms of this ecologically safe microbial insecticide, and included the first evidence of multiple mechanisms of insect resistance to microbial insecticides. This information is important for the development of effective strategies using both Bt-based and other biopesticides in transgenic plants, and also for preventing insect adaptation to biopesticides used in pest management programs.
4. Development of chicken avidin as a biopesticide in transgenic corn. New biopesticides are needed for use in transgenic plants to enhance resistance to insects and pathogens. Kramer's research group has developed an insect gut-targeted biopesticide, the protein avidin from chicken, which causes a vitamin (biotin) deficiency in insects and ultimately leads to stunted growth and mortality. They demonstrated that avidin is an insecticidal and/or insect growth-inhibiting dietary protein for many species. In collaborative research with two biotechnology companies (ProdiGene/Pioneer), the gene for avidin was transferred to corn and the transgenic seed obtained was shown to be resistant to both internal and external grain-feeding insect pests. Avidin is a unique biopesticide whose effects can be completely reversed by supplementation with an antidote, biotin, or completely inactivated by heat treatment. Preliminary experiments showed that avidin corn was not toxic to mice. Development of this transgene as a defense gene in corn, wheat, rice, sorghum and other plants is ongoing. Potential applications of avidin grains include their use for resistance to field crop pests in addition to post-harvest pests. Alternatively, avidin grains may be used directly as insecticides as well as in bait programs for a variety of insect pests. See Avidin: An Egg-Citing Insecticidal Protein in Corn (also available in pdf).
5. Development of digestive enzyme inhibitors as potential biopesticides in transgenic plants. Amylases and proteinases in the insect digestive system are critical enzymes required for normal growth and development. Genes for amylase and proteinase inhibitors can be used to improve the resistance of cereals to storage pests via host plant resistance genetic engineering or traditional breeding programs. Kramer and his collaborators have characterized some of these digestive enzymes from stored product beetles, and several proteinaceous inhibitors from wheat, rice, corn, and beans have been isolated and characterized. Many of the inhibitors were selective for insect digestive enzymes and suppressed the growth of insects when administered in semi-artificial diets. These results provided knowledge at the molecular level about a natural defense mechanism used by plants to deter insect predation and also demonstrated that some of the amylase and proteinase inhibitors can be utilized as biopesticides in transgenic plants.
6. Development of insect growth regulators as grain protectants.
Kramer's research group demonstrated that several juvenile hormone
mimics, cuticle inhibitors, and other materials are effective as
stored product protectants and also delineated the metabolism of
juvenile hormone in several species of stored product insects. Two
commercially available compounds, methoprene and fenoxycarb, were
found to be very active towards stored product beetles and moths.
Some of these data were utilized by Zoecon Corporation in 1988 and
Maag Agrochemical Corporation in 1989 to support registrations of
those compounds for stored product insect pest control. Kramer also
helped to design and evaluate another compound, 5-([5-13-butyl-3-methyloxiranyl)-3-methyl-2
pentenyl] oxy)-2-ethylpyridine, that was one of the most active
insect growth regulators ever produced. Kramer and his collaborators
also evaluated projuvenoid derivatives of fenoxycarb that are metabolically
activated by target insects. He and his colleagues also revealed
how juvenile hormone titer is regulated during insect development
by the interplay of specific hormone carrier proteins and both synthetic
and hydrolytic enzymes. This research helped to establish that insect
growth regulators of the juvenile hormone-type, cuticle inhibitor-type,
and several natural products can be used to control stored product
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