Anthony Infante

Professor, Molecular Biology and Biochemistry Department
Ph.D. (Biochemistry) University of Pennsylvania

ainfante@wesleyan.edu | 860-685-2424

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Gene regulation in embryo genesis; molecular mechanisms of cellular defenses against oxidative stresses.

The main focus of our research is on the control of gene expression in a developing multicellular organism, the sea urchin embryo. During the early stages of embryonic development in this system, as well as in many others, there is considerable regulation of protein synthesis at the level of messenger RNA utilization. Our interest is to understand the mechanisms underlying such transnational-level control. A range of biochemical and molecular biological approaches are being employed in these investigations.

Current research projects include studies of:

Distribution of different mRNAs between polysomal and non-polysomal fractions of embryos at different developmental stages. We have analyzed these two populations of mRNAs by cell-free translation and two-dimensional gel electrophoresis and are extending our analysis with cloned gene sequences. Messenger RNA species that display specific regulated translation are being identified by employing cDNA recombinant libraries and by DNA sequencing.

The synthesis and role of small cytoplasmic RNAs and RNPs in translational control during development and heat shock. We have been studying in particular 7SL RNA, which is a component of the signal recognition particle. This particle is involved in the regulation of synthesis of at least some glycoproteins.

Developmental and ionic regulation of the heat shock response in sea urchin embryos, with particular interest in the effects of iron on embryo genesis, and on alterations in gene expression and protein synthesis. Iron is critically involved in the production of oxygen-free radicals that have been implicated in adversely affecting cellular processes and in damaging DNA. The regulation of expression of the iron-binding protein ferritin is being examined both in sea urchins and yeast with the intent of determining the role of this protein in protecting cells from the deleterious effects of oxygen-free radicals.

The deleterious effect of excess iron upon the early development of sea urchin embryos is shown. In (A) are 32-64 cell embryos grown in normal sea water; this stage is reached in six hours after fertilization of the eggs. In B, C and D are embryos grown for six hours in sea water containing 0.1 mM, 0.5 mM, and 1.0mM iron (Fe++), respectively; abortive, abnormal development is evident in these embryos. Our experiments suggest that the iron is causing this damage via its catalytic role in the productions of oxygen free radicals. The hydroxyl radical (HO.) is known to damage many cellular constituents. The ability of the embryo to detoxify excess iron increases during embryonic development. The biochemical mechanisms underlying this acquired tolerance are being investigated

Selected Publications

Infante, A. A., Infante, D. and Chan. M-C. (2004). Identification and Characterization of Ferritin in the Nucleus and the Microtubule Marginal Band of Mature Avian Red Blood Cells. (manuscript in preparation).

Anthony Infante, Dzintra Infante, Muh-Chun Chan, Poh-Choo How, Irena Linhartová, Gerhard Wiche, Friedrich Propst, Ferritin association with marginal band microtubules and nuclei of differentiating and mature chicken erythrocytes, submitted (in review)

Infante, A. A., D. Infante and M. Nemer. Ferritin Gene Expression is Spacially Restricted to the Micromeres of Early Sea Urchin Embryos (in preparation).

Infante, A. A., E. C. Thomborrow, K. Geoghegan and D. Infante. The Anti-Metastasis Protein nm23/NDPkinase is Induced by Heat Shock and is Developmentally Regulated in S. cerevisae (in prepartation).

Mikulitis.W., Schranzhofer, A. Bauer, H. Dolznig, L. Lobmayr, A. A. Infante, H. Beug, E. Mullner. "Impaired Ferritin mRNA Translation in Primary Erythroid Progenitors: Switch to Iron-Dependent Regulation by the v-ErbA Oncoprotein". BLOOD. 94:4321-4332 (1999). (December 15 issue)

Mikulits, W, T.Sauer, A.A.Infante, E.W.Mullner. "Structure and Function of the Iron Responsive Element from Human Ferritin L Chain mRNA. Biochem. Biophys. Research Communications. 235:212-216 (1997).

Thornborrow, E. C., Donovan, M., and Infante, A. A. Variations in Ferritin Subunit Size Correlate with Survivability of Yeast to Heat and Oxidative Stress. Molecular Biology of the Cell 5, 218a (1994).

Loeber, G., Dworkin, M. B., Infante, A. A. and Ahorn, H.  Characterization of Cytosolic Malic Enzyme in Human Tumor Cells.  FEBS Letters 344, 181-186 (1994)

Infante, A.A., Infante, D. and Rimland, J. Ferritin Gene Expression is Developmentally Regulated and Induced by Heat Shock in Sea Urchin Embryos. Development Genetics 14, 58-68 (1993).

LeBlanc, J.M. and Infante, A.A. Sea Urchin Small RNA RNPs: Identification, Synthesis, and Sub-Cellular Localization During Early Embryonic Development. Molecular Reproduction and Development 31, 96-105 (1992).

Loeber, G., Infante, A.A., Mauer-Fogy, I. and Dworkin, M. Human NAD+-dependent Mitochondrial Malic Enzyme: cDNA Cloning, Primary Structure and Expression in E. coli. J. Biological Chemistry 266, 3016-3021 (1991).

Nemer, M. Rondinelli, E., Infante, D. and Infante, A.A. Polyubiquitin RNA Characteristics and Conditional Induction in Sea Urchin Embryos. Developmental Biology 145, 255-265 (1991).

LeBlanc, J.M. and Infante, A.A. Endoplasmic Reticulum Associated Glucose-6-Phosphatase Activity is Developmental Regulated and Enriched in Microsomes of Endo/Mesoderm in Sea Urchins. Roux’s Arch. of Developmental Biology 199, 102-106 (1990).

Infante, A.A., Rimland, J., Geoghegan, K., Lanzetti, A., Hurwitz, J. and Infante, D. Developmental Regulation of the Heat Shock Response in Sea Urchin Embryos: Ferritin as a Heat Shock Protein. “HEAT SHOCK” Inter. Inst. Genetics & Biophysics; Naples. Vol. 3, 132 (1990).