Undergraduate
Research Projects
HAROLD B. WHITE, III
Professor of Biochemistry
Phone: (302) 831-2908
e-mail: halwhite@udel.edu
CURRENT RESEARCH INTERESTS
Science Education: Developing Classroom Demonstrations for PBL Classes
Bioinformatics: Biased Codon Usage
Riboflavin Metabolism:
Molecular Zip codes,
Sudden Infant Death Syndrome,
Cholesterol Biosynthesis
Please note, my current research efforts involve undergraduates only.
Bioinformatics:
Baised Codon Usage.
Selection for efficiency in protein synthesis on highly expressed genes
results in the preferential use of restricted sets of codons that have
coevolved with corresponding sets of abundant tRNAs. Different organisms
can have quite different preferred sets. In principle, translation efficiency
could be increased further if aminoacyl-tRNAs could queue in-phase on the
mRNA prior to entering the ribosomal A-site in a process occurring simultaneously
with peptidy transfer and translocation. Selection for such parallel processing
should enhance the comma-free character of highly expressed genes. Does
it? If you have computers skills and an interesting in mining the genome
data bases, this might be a project for you.
Riboflavin
Metabolism:
Virtually all metabolic pathways depend on oxidation-reduction
reactions coupled to derivatives of riboflavin,
also known as Vitamin B2. Little surprise then that riboflavin
deficiency can cause death as it does in about 13 days for chicken embryos
developing in riboflavin-deficient eggs laid by a particular strain of
hens. Due to a mutation
in the gene encoding riboflavin-binding protein, these hens cannot deposit
riboflavin in their eggs. Research in my laboratory revolves around the
metabolic consequences of riboflavin deficiency, the metabolism of riboflavin,
and the structure, function, and evolution of riboflavin-binding protein.
While riboflavin provides a unifying theme, the problems addressed require
multi-disciplinary thinking, diverse experimental skills, and collaboration
with other scientists. Resourceful, self-motivated, and intellectually
curious students may work on problems such as those that follow.
Molecular ZIP Codes. Virtually every molecule assimilated or produced by our body seems to "know" where it belongs. How molecules move from one specific place to another constitutes a prominent theme in contemporary biochemical research. Such issues apply to vitamins. For example, how is riboflavin from the diet assimilated and distributed to various tissues according to the different needs of those tissues? More specifically for research in this laboratory, how is riboflavin delivered to the hen oocyte, the large, nutrient-rich ovarian cell that becomes the yolk of a chicken egg? We know that riboflavin-binding protein, synthesized in the liver and secreted into the blood stream, scavenges riboflavin and the maturing oocyte removes the vitamin-protein complex from the blood. There the oocyte cell membrane recognizes some structural feature of riboflavin-binding protein or associated proteins. What is the chemical nature of this molecular ZIP Code?
Sudden Infant Death Syndrome. Metabolically, a rapidly growing chicken embryo that dies in a riboflavin-deficient egg resembles in intriguing ways some cases of sudden infant death syndrome (SIDS) in humans. While it is certain that few, if any, SIDS deaths are due to riboflavin deficiency, the similarities suggest that an understanding of the progression of metabolic events leading to sudden death of chicken embryos may enable doctors some day to recognize and treat infants at risk for SIDS. Consequently we study changes in metabolites and enzyme activities as a function of embryonic age. Associated with this work are instrument-development projects including an embryonic heart monitor and an NMR probe to measure phosphorylated metabolites within embryos in incubating eggs.
Dependence
of Cholesterol
Biosynthesis on Flavins. Everyone knows
that egg yolk is loaded with cholesterol. Therefore, it would be reasonable
to assume that chick embryos would not need to synthesize cholesterol.
Not so! Embryos developing in riboflavin-deficient eggs accumulate squalene
in their brains before they die on the 13th day of incubation. Squalene
is a precursor of cholesterol that does not accumulate in normal chick
embryos. While the death of riboflavin-deficient embryos has been attributed
to a severe impairment in the oxidation
of fatty acids, a process very dependent on flavin coenzymes, it is
possible that squalene disrupts neural processes and contributes to the
cause of death. How would one test this hypothesis?
RECENT PUBLICATIONS
Virginia A.M. Abrams, Chih-Chiang Han, and Harold B. White, III, "Riboflavin-Deficient Chicken Embryos: Hypoglycemia Without Dicarboxylic Aciduria," Comparative Biochem. Physiol. (1995) 111B, 233-241.
Christine M. Lee and Harold B. White, III, "Riboflavin-Binding Protein Induces Early Death of Chicken Embryos," J. Nutrition (1996) 126, 523-528.
Harold B. White, III, "Sudden Death of Chicken Embryos with Hereditary Riboflavin Deficiency, J. Nutrition (1996) 126, 1303S-1307S.
Amandio V. Vieira, Harold B. White, III, and Päivi M. Vieira, "Detection of a Chicken Oocyte Membrane Receptor for Biotin-Binding Protein," FEBS Letters (1996) 382, 183-185.
Karen Hoober, Bhavana Joneja, Harold B. White, III, and Colin Thorpe, "Sulfhydryl Oxidase from Chicken Egg White," J. Biol. Chem (1996) 271, 30510 - 30516.
Harold B. White, III, "Competitive Binding Assays for
Biotin-Binding Protein," Methods in Enzymology: Vitamins and Coenzymes,
Volume 279 Part I, 464-466 (1997).