Massachusetts Institute of Technology

The General Hospital Corporation

Other

H Robert Horvitz

Junying Yuan

Shai Shaham

Rajesh Ranganathan

Daniel R Rosen

Robert A Brown

Xiaowei Lu

Stephen C Cannon

Michael Hengartner

Michael Koelle

Robert Brown

Eric A Miska

Barbara Conradt

Ezequiel A Alvarez-Saavedra

Ewa M Davison

Ho Yon Hwang

Described herein is the discovery that human interleukin-1&#x3b2; convertase (ICE) is structurally similar to the protein encoded by thecell death gene, ced-3. Comparative and mutational analyses of the two proteins, together with previous observations, suggest that the Ced-3 protein may be a cysteine protease like ICE and that ICE may be a human equivalent of the nematode cell death gene. Another mammalian protein, the murine NEDD-2 protein, was also found to be similar to Ced-3. The NEDD-2 gene is implicated in the development of the murine central nervous system. On the basis of these findings, novel drugs for enhancing or inhibiting the activity of ICE, ced-3, or related genes are provided. Such drugs may be useful for treating inflammatory diseases and/or diseases characterized by cell deaths, as well as cancers, autoimmune disorders, infections, and hair growth and hair loss. Furthermore, such drugs may be useful for controlling pests, parasites and genetically engineered organisms. Furthermore, novel inhibitors of the activity of ced-3, ICE and related genes are described which comprise portions of the genes or their encoded products.

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The invention provides novel lin-8, lin-56, and lin-61 genes and polypeptides involved in cell fate determination and in cell proliferation. In addition, the invention includes mutants of these three genes, as well as methods for utilizing these genes, and their encoded polypeptides, in diagnosing and treating abnormal cell proliferation.

The invention relates to methods and compositions for microRNA expression analysis using microarrays.

High throughput methods relating to microRNA expression analysis

The invention generally features sqv nucleic acid and polypeptide molecules associated with connective tissue diseases, progeroid disorders, and aging, and methods for isolating such molecules.

SQV nucleic acids and polypeptides

The invention features substantially pure nucleic acid sequences encoding wild-type or mutant serotonin reuptake transporter (SERT) polypeptides, as well as the polypeptides themselves. The invention also features methods for identifying modulators of the biological activity of a SERT and for identifying if such a modulator has a secondary target. In addition, the invention features methods for treating a condition in a subject.

CeSERT genes, proteins, and modulatory compounds

Described herein are genes shown to be essential for programmed cell death in, their encoded products (RNA and polypeptides), antibodies directed against the encoded polypeptides; probes for identifying structurally related genes and bioassays for identifying functionally related cell death genes from various organisms; methods and agents for altering (increasing or decreasing) the activity of the cell death-genes and, thus, of altering cell death; and uses therefor. Specifically, two genes shown to be essential for almost all of the cell deaths which occur in the development of, referred to as ced-3 and ced-4, have been cloned, sequenced and characterized.

Cloning sequencing and characterization of two cell death genes and uses therefor

Disclosed is a novel serotonin-gated anion channel that is permeable to chloride ions. Also disclosed are methods for the screening of therapeutics useful for treating serotonin-mediated cellular responses and conditions, as well as diagnostic methods for identifying such conditions.

Serotonin-gated anion channel

The invention provides novel genes involved in cell fate and cell proliferation, including lin-37, lin-35, lin-53, lin-55, lin-52, and lin-54 in multiple species and an E2F-1 gene of C. elegans. Methods for utilizing the genes and encoded proteins are also provided.

Altered human interleukin-1&#x3b2; convertase (ICE), NEDD-2, and C. elegans ced-3 polypeptides and uses therefor

The present invention relates to genes, referred to herein as cell death-protective genes, which protect cells against programmed cell death by antagonizing the activities of genes which cause cell death. As described herein, a cell death-protective gene from the nematode, called ced-9 has been identified, sequenced, and characterized. In addition, mutations which inactivate the ced-9 gene are also described.

Identification and characterization of a gene which protects cells from programmed cell death and uses therefor

The invention features substantially pure nucleic acid sequences encoding wild-type or mutant serotonin retake transporter (SERT) polypeptides, as well as the polypeptides themselves. The invention also features methods for identifying modulators of the biological activity of a SERT and for identifying if such a modulator has a secondary target. In addition, the invention features methods for treating a condition in a subject.

Disclosed is the family of genes responsible for the neurodegenerative diseases, particularly Amyotrophic Lateral Sclerosis. Methods and compounds for the diagnosis, prevention, and therapy of the disease are also disclosed.

Mice having a mutant SOD-1-encoding transgene

The invention provides a novel protein, EGL-1, involved in cell death and methods for identifying compounds and genes which affect the cell death pathway.

Growing community of inventors

Auburndale, MA, United States of America

H Robert Horvitz