Exelixis, Inc.

Casey Kopczynski

Darren Platt

Andrew Roy Buchman

John William Winslow

Lori Friedman

Jeffrey Scott Larson

Helen Louise Francis-Lang

Felix D Karim

Bindu Priya Reddy

Yuling Luo

Candace Swimmer

Kevin Patrick Keegan

Stephanie A Robertson

Geoffrey Duyk

Jonathan Cagampang Heller

Jonathan Scott Margolis

Lynn Marie Young

Christian Burks

Michael Martin Ollman

Lucile A Gillett

Madelyn Robin Demsky

Jenny Kopczynski

A family of p53 tumor suppressor nucleic acid and protein isolated from several insect species is described. The p53 nucleic acid and protein can be used to genetically modify metazoan invertebrate organisms, such as insects and worms, or cultured cells, resulting in p53 expression or mis-expression. The genetically modified organisms or cells can be used in screening assays to identify candidate compounds that are potential pesticidal agents or therapeutics that interact with p53 protein. They can also be used in methods for studying p53 activity and identifying other genes that modulate the function of, or interact with, the p53 gene. Nucleic acid and protein sequences for Drosophila p33 and Rb tumor suppressors are also described.

Insect p53 tumor suppressor genes and proteins

Methods, transformation constructs, and transgenic animals for identifying anti-tumor agents and anti-tumor drug targets are described. The transformation constructs are used to generate transgenic animals that have altered expression of an oncogene or tumor suppressor gene in a target tissue that is dispensable for viability and reproduction. In some embodiments, the altered expression results in abnormal proliferation of the target tissue and normal proliferation in all other tissues. Anti-tumor drug targets can be identified by generating progeny of the transgenic animals that have mutations in various genes. Gene mutations that result in a specific reduction or killing of the target tissue are identified as possible anti-tumor drug targets and are further evaluated. Anti-tumor agents are identified that mimic the effect of the gene mutations that result in specific reduction of the target tissue. Alternatively, anti-tumor agents can be identified by administering various compounds directly to the transgenic animals, or their progeny, and selecting as putative therapeutic agents, compounds that result in target-tissue specific antiproliferation.

Methods for identifying anti-cancer drug targets

Tandem pore domain weak inward rectifying K (TWIK) channel nucleic acids and proteins that have been isolated from and Leptinotarsa are described. The TWIK channel nucleic acids and proteins can be used to genetically modify metazoan invertebrate organisms, such as insects, coelomates, and pseudocoelomates, or cultured cells, resulting in TWIK channel expression or mis-expression. The genetically modified organisms or cells can be used in screening assays to identify candidate compounds which are potential pesticidal agents or therapeutics that interact with TWIK channel proteins. They can also be used in methods for studying TWIK channel activity and identifying other genes that modulate the function of, or interact with, the TWIK channel gene.

Nucleic acids and polypeptides of invertebrate TWIK channels and methods of use

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Belmont, CA, United States of America

Casey Kopczynski