Areas Richard Burger is Knowledgeable in:
Antibiotic modes of action, enzyme mechanisms, biological fitness
Techniques Richard Burger Uses:
I design, execute and write up experiments. I also comment extensively on other workers' approaches, results, and their significance (at meetings, seminars, review groups, etc.)
Richard Burger's Problem Solving Skills:
- Technical writing: Grant applications, patent applications, research papers and reviews
- Pharmaceutical: I worked six years on drug development, testing & regulation, up to Chief Scientist, at a start-up.
- Chemistry: I have taught Inorganic Chemistry, and Biochemistry to uperclass undergraduates, and published in chemical journals
- Microbiology: I have used bacteria, viruses and protozooa in several published studies
- Music: I sight-read and perform renaissance motets a cappela, plus other material, sometimes paid
- Life Sciences: I have devised and taught courses in Molecular Biology and in Human Biology
- Biomedical: I have studied the interactions of pathogens with model organisms, and chaired my Institute's IACUC
- Biology: I can (and have) grow, medicate and dissect animals and plants and study the contents of their tissues
- Safety: I served as Institute Safety Officer and Radiation Safety Officer for several years
Richard Burger's Problem Solving Experience:
- I supervised (administratively and scientifically) an extensive pre-clinical program of animal-testing novel metallo-organic agents for effacacy against epithelial herpetic keratitis
- I initiated and pursued a colaborative program of structural studies by ENDOR spectroscopy of bleomycin-DNA interactions, exploiting the nuclear magnetic moments of O, P, H, Fe, and F isotopes
- I devised a simple, capilary-based viscosity measurement of fresh bacterial lysates' DNA strand-cleavage to monitor fluoroquinolone action
- I conceived and utilized a real-time NMR procedure to monitor the sequence of bond breakages in DNA following attack by bleomycin, and analized the results' mechanistic implications
- I showed that, contrary to accepted models, superoxide protects E. coli from bleomycin-mediated lethality
- I set up and used (under contract) a procedure for monitoring the killing of the pathogen Acanthomeba by various contact lens washing agents
- I devised and performed a series of very accurate measurements of an O-18 kinetic isotope effect I discovered on activated bleomycin decay, which indicated that the rate-limiting process was an O-O cleavage event
- I discovereded that Manganese can function as an iron analogue in facilitating bleomycin to attack DNA, but only when activated by hydrogen peroxide
- I devised procedures for resolving individual steps in the degradation of DNA (including real-time viscometry and plasmid-nicking fluorimetry) following bleomycin attack and made inferences in ruling out putative reaction pathways: especially resolving DNA strand cleavage from base propenal release
- I discovered new optical effects of activity-enhancing phosphate compounds on Fe(II)-bleomycin (in the absense of oxygen), distinguishing these changes from oxygen-mediated effects, and characterizing the binding strength and molecularity of the complexes formed
- I devised a precise way to characterize the redox state of activated bleomycin, analyzing the kinetic effects of reductants as they competed with the spontaneous degradation of this unstable species.
- I devised a way to trap a short-lived, EPR-silent iron-bleomycin intermediate for Moessbauer characterization: inhibiting its disproportion by presenting it with an excess of DNA, which the drug binds
- I showed that the stability of activated bleomycin, once formed, did not depend on oxygen, but that its products did, and in yields that did not implicate a simple oxygen-dependent choice of pathways
- I demonstrated stoichiometrically that the only pathway of bleomycin-induced DNA cleavage was that forming base propenal as a DNA end product
- I showed by a variety of techniques (including radioisotope-ratio procedures) to show how bleomycin-degraded DNA produced a nucleic base derivative, and showed that this was but one product (dependent on oxygen availability) of devided reaction pathways of activated bleomycin. And I devised two procedures to produce activated bleomycin in the absence of oxygen.
- I characterized the effects of oxygen analogues on the activity and spectra of bleomycin, and showed that the drug perminantly self-inactivated in the course of its interaction with iron(II) and oxygen in the absense of DNA, its target
- I detected fleeting oxo-iron-bleomycin intermediates by optical stopped-flow spectroscopy and trapped two forEPR characterization by freeze-quench techniques.
- I showed that rapidly-renaturning (crosslinked) DNA is not an intermediate in E. coli DNA replication
- I discovered, characterized, and named (Activated Bleomcin) the kinetically competent form of bleomycin that attacks DNA
- I devised procedures to purify and characterize mamalian 5'-nucleotidase from a good source I discovered
- I discovered that neocarzinostatin requires oxygen gas for its DNA-cleaving activity
- I helped define the effects of metabolites on the bleaching of Euglena by Streptomycin-type antibiotics
- I devised a density-labeling procedure that showed that toluene-treated (permeablized) E. coli resume replicating their DNA at the place they left off at the time of treatment
- I devised an isotope-dilution procedure to evaluate the flux in branched metabolic pathways, and applied it to mamalian adenylate metabolism
- I discovered the photo-lability of activated bleomycin and showed that its degradation of DNA could be triggered by light, using low-temperature liquid protocols and cryogenic procedures. I used EPR spectroscopy with O-17 activated bleomycin or O-17 water to show that the O-O cleavage produced a water-level product that remained close to the iron in 77K incubations.
- I determined the organ-distribution paterns of nucleotide-regulated adenosine deaminase in mamalian tissues
- I discovered how to surface-sterilize and germinate axenic Drosera (an insectivouous plant)
- I proposed and verified that superoxide could participate in activating the first-line anti-tuberculosis pro-drug isoniazid in vivo