Section: Research

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Phillip Zamore, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Interdisciplinary Graduate Program

Gretchen Stone Cook Professor of Biomedical Sciences

Dissecting the RNAi and miRNA pathways

RNA interference (RNAi) is the surprising ability of double-stranded RNA — but not antisense RNA — to target a corresponding mRNA for destruction.  RNAi likely represents an ancient cellular defense against viral infection, a mechanism for preventing the ‘jumping’ of transposons, and perhaps even a pathway by which cells regulate endogenous genes.  RNAi has become an important tool for studying gene function in worms, flies, and cultured mammalian cells, and may lead to new drugs to treat human genetic disorders.  Our laboratory studies the mechanism that underlies RNAi in plants and animals.  The laboratory combines biochemistry with genetics and cell biology to understand the biological functions and the molecular basis of the RNAi pathway.      

We also study a related pathway, the microRNA (miRNA) pathway.  miRNAs are small RNAs found in animals and plants; they regulate gene expression by mechanisms intimately related to those that underlie RNAi.  We are particularly interested in how miRNAs find identify their target genes and how they repress their expression.

Understanding the molecular mechanisms of post-transcriptional gene regulation.

How do animal embryos regulate the localization, translation, and stability of mRNAs?

In Drosophila, mRNA encoding the transcription factor, hunchback, is present throughout the embryo, but is translated into protein only in the anterior half of the cell.  Two proteins, NANOS and PUMILIO. are required to repress hunchback translation in the posterior half of the fly embryo.  PUMILIO binds RNA through a novel RNA-binding motif found in proteins that control developmental decisions in yeast, slime mold, and worms, and is more than 80% identical to a protein of unknown function in humans.  A major goal of our laboratory is to learn how PUMILIO and NANOS control hunchback mRNA translation and to determine the biological role of the human PUMILIO protein.

For more information, visit his Howard Hughes Medical Institute web page at: http://www.hhmi.org/research/investigators/zamore_bio.html

Office: LRB 822, Lab 870 L-P
Phone: 508-856-2191
E-mail: Phillip.Zamore@umassmed.edu
Keywords: RNA Biology, RNA Interference (RNAi), Developmental Biology, Biochemistry, Chemical Biology

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