Peptidomimetics

We are preparing novel peptidomimetic structures based on allenes. The almost unique geometric properties of allenes makes them ideal mimics for disulfide bonding, which is crucial in establishing secondary, tertiary, and even quaternary structures in proteins. We believe allenes can most effectively mimic the structure of cystine, and that allene "clips" can be introduced into native peptide sequences using novel ring-closing metathesis processes.

New detection methods using luciferase

This project is aimed at significantly enhancing the utility of firefly luciferase for biological assays, in vivo imaging/ microscopy, and photodynamic therapy. Our primary approach is preparing and studying with luciferase a wide variety of new luciferin relatives.

Firefly

Chemical genetics

Chemical genetics is the use of small organic compounds to mimic the effects of gene knockouts. The ability of compounds to be applied at graded levels and with temporal control adds considerable power beyond conventional genetic methods to discover gene function (forward chemical genetics), since phenotypes that might be lethal at earlier stages in development can be observed. Chemical genetics can also be used to induce novel phenotypes (reverse chemical genetics) that are not readily discovered by conventional genetic approaches.

Our earlier work has used chemical genetics to study insulin signaling in Drosophila. Current projects focus on the discovery of novel molecules that cause phenotypic changes in plant cells based on vacuolar sorting.

Treatment of mutant Drosophila with a phosphoinositol-3-kinase inhibitor reverses a bulging eye phenotype due to over-expression of insulin receptor in the eye

Our chemical genetics work is being performed in collaboration with Prof. Natasha Raikhel of the UCR Center for Plant Cell Biology.

Erika L. Hensley, Michael C. Pirrung, and Richard G. Fehon, ”Chemical Genetics of Insulin Signaling via Phosphatidylinositol-3-Kinase (PI3K) in Drosophila,” in press (2007).

RNA microarray analysis

We are also developing novel applications of DNA chips, particularly in the area of analysis of RNA. DNA chips give us the power to analyze variant mRNA splice forms or the short, interfering RNA molecules recently shown to be important in post-translational gene silencing.

Link to a DNA Chip web site. http://www.gene-chips.com

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