University of California

Cold Spring Harbor Laboratory

Jasper D Rine

Matthew N Ashby

Randolph Hampton

Bruce W Stillman

Ira Herskowitz

Ryuji Kobayashi

Masumi Hidaka

Kimberly Gavin

Joachim Li

Victor L Boyartchuk

Patricia Laurenson

Francis J McNally

Margit Foss

Stephen P Bell

Ann Bowling

Danika Metallinos

Mathew Ashby

Two genes which encode polypeptides that mediate post-prenylation processing steps in CAAX polypeptides such as Ras are provided. The two genes (AFC1 and RCE1) encode polypeptides that mediate the removal of the AAX tripeptide from the CAAX polypeptide following prenylation. The genes and encoded polypeptides provide assays for testing compounds for an effect on post-prenylation processing steps. A heat shock assay for assessing Ras activity is also provided.

AFC1 and RCE1: isoprenylated CAAX processing enzymes

Stimulus-response patterns are analyzed using deduction protocols applied through AI systems such as expert systems and neural networks. Generating an output signal matrix database involves: (i) constructing a stimulated physical matrix; (ii) detecting a physical signal at each unit of the physical matrix; (iii) transducing each physical signal to generate an electrical output signal; (iv) storing each output signal in an output signal matrix data structure; and (v) repeating steps (i)-(iv) to iteratively store output signal matrix data structures for a plurality of stimuli to form an output signal matrix database. Individual output signal matrices are compared to such output signal matrix databases according for qualitative analysis. The stimulated physical matrices comprise an ordered array of units, each confining (1) either a different responder of a living thing or a probe corresponding to such a different responder and, (2) an identifier for the responder or probe. The living thing is provided a stimulus capable of repressing the responders of a plurality of the units and the identifier provides a physical signal corresponding to the repression of such different responder.

Systems for generating and analyzing stimulus-response output signal matrices

The present invention provides isolated nucleic acid sequences which encode a family of HMG-CoA Reductase Degradation (HRD) polypeptides. More particularly, the present invention provides isolated HRD1, HRD2 and HRD3 nucleic acids and the Hrd polypeptides encoded by such nucleic acids, i.e., Hrd1, Hrd2 and Hrd3, respectively. Vectors comprising the nucleic acids are provided. In addition, the present invention provides screening assay related to cholesterol biosynthesis.

Genes and proteins controlling cholesterol synthesis

The horse endothelin-B receptor gene has been identified, isolated, purified, sequenced and mapped. The horse endothelin-B receptor gene is associated with Lethal White Foal Syndrome. A PCR based assay has been developed to identify a specific mutation in the endothelin-B receptor gene associated with Lethal White Foal Syndrome. The cDNA clone for the horse endothelin-B receptor has been isolated and purified. Molecular genetics probes for the horse endothelin-B receptor gene and gene products are presented.

Horse endothelin-B receptor gene and gene products

Systems for generating and analyzing stimulus-response output signal

Origin of Replication Complex (ORC) genes, nucleic acids which encode ORC proteins and hybridization reagents, probes and primers capable of hybridizing with ORC genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant ORC protein, a natural intracellular ORC protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said ORC protein selectively binds said binding target; and detecting the presence or absence of specific binding of said ORC protein to said binding target.

Origin of replication complex genes

Origin of replication complex genes and methods of using the same

Methods and compositions for modeling the transcriptional responsiveness of an organism to a candidate drug involve (a) detecting reporter gene product signals from each of a plurality of different, separately isolated cells of a target organism, wherein each cell contains a recombinant construct comprising a reporter gene operatively linked to a different endogenous transcriptional regulatory element of the target organism such that the transcriptional regulatory element regulates the expression of the reporter gene, and the sum of the cells comprises an ensemble of the transcriptional regulatory elements of the organism sufficient to model the transcriptional responsiveness of said organism to a drug; (b) contacting each cell with a candidate drug; (c) detecting reporter gene product signals from each cell; (d) comparing reporter gene product signals from each cell before and after contacting the cell with the candidate drug to obtain a drug response profile which provides a model of the transcriptional responsiveness of said organism to the candidate drug.

Methods for drug screening

Growing community of inventors

Moraga, CA, United States of America

Jasper D Rine