Abstract: The present invention relates to variants of TNF family ligands which have been mutated at the ligand trimerisation interface so that they are not capable of assembling into trimers, and either assemble into dimers or remain as monomers. Such ligands bind to the TNF receptor but are unable to activate it, effectively functioning as competitive inhibitors. The invention also relates to nucleic acids encoding the variants of TNF family ligands, vectors and host cells comprising the nucleic acid and methods for the treatment of diseases associated with aberrant signalling through a TNF receptor.

Abstract: The present invention relates to novel cytokines, which have a modified selectivity/specificity for their cognate receptors. In particular, the invention relates to a variant TRAIL protein, which has superior selectivity for the death receptor 4 (TRAIL-RI) over the death receptor 5 (TRAIL-R2). In addition, the invention relates to a variant TRAIL protein which exhibits superior selectivity for the death receptor 4 (TRAIL-R1) over the decoy receptors DcR1 (TRAIL-R3) and DcR2 (TRAIL-R4).

Abstract: The present invention relates to novel methods for the design of proteins, in particular, cytokines. These methods allow the stabilisation of such cytokines, as well as modification of their selectivity/specificity for their cognate receptors. The invention also relates to various modified proteins that have been designed by the methods of the invention.

Abstract: The present invention provides a method for screening for the effect of a test agent on a population of biological specimens, preferably insects, comprising the steps of providing a population of specimens, administering at least one test agent to the population, creating a digitized movie showing the movements of members of the population, measuring at least one trait of members of the population, and correlating the traits of the population with the effect of the test agent. The invention also provides a method for preparing a medicament useful for the treatment of a mammalian disease.

Abstract: A method of system is provided for assaying specimens. In connection with such system or method, plural multi-pixel target images of a field of view are obtained at different corresponding points in time over a given sample period. A background image is obtained using a plural set of the plural target images. For a range of points in time, the background image is removed from the target images to produce corresponding background-removed target images. Analysis is performed using at least a portion of the corresponding background-removed target images to identify visible features of the specimens. A holding structure is provided to hold a set of discrete specimen containers. A positioning mechanism is provided to position a plural subset of the containers to place the moving specimens within the plural subset of the containers within a field of view of the camera.

Abstract: The present invention relates to novel methods for the design of proteins, in particular, cytokines. These methods allow the stabilisation of such cytokines, as well as modification of their selectivity/specificity for their cognate receptors. The invention also relates to various modified proteins that have been designed by the methods of the invention.

Abstract: The invention relates to methods for the stabilisation of cytokines and to cytokines generated by such methods. The methods of the invention involve mutating the amino acid sequence of a cytokine so as to remove solvent-exposed hydrophobic residues, and/or mutating the amino acid sequence of the cytokine so as to stabilise one or more secondary structure elements in the molecule. These steps have the effect of destabilsing intermediates that are formed during the folding process, relative to the stability of the cytokine in its naturally folded state, so increasing the yield of the cytokine as produced in vitro.

Abstract: The present invention provides a method for screening for the effect of a test agent on a population of biological specimens, preferably insects, comprising the steps of providing a population of specimens, administering at least one test agent to the population, creating a digitized movie showing the movements of members of the population, measuring at least one trait of members of the population, and correlating the traits of the population with the effect of the test agent. The invention also provides a method for preparing a medicament useful for the treatment of a mammalian disease.

Abstract: A method of system is provided for assaying specimens. In connection with such system or method, plural multi-pixel target images of a field of view are obtained at different corresponding points in time over a given sample period. A background image is obtained using a plural set of the plural target images. For a range of points in time, the background image is removed from the target images to produce corresponding background-removed target images. Analysis is performed using at least a portion of the corresponding background-removed target images to identify visible features of the specimens. A holding structure is provided to hold a set of discrete specimen containers. A positioning mechanism is provided to position a plural subset of the containers to place the moving specimens within the plural subset of the containers within a field of view of the camera.

Abstract: The present invention provides a method for screening for the effect of a test agent on a population of biological specimens, preferably insects, comprising the steps of providing a population of specimens, administering at least one test agent to the population, creating a digitized movie showing the movements of members of the population, measuring at least one trait of members of the population, and correlating the traits of the population with the effect of the test agent. The invention also provides a method for preparing a medicament useful for the treatment of a mammalian disease.

Abstract: Tools are provided for obtaining and assessing data concerning the physical or behavioral traits of an biological specimen population for the purpose of identifying, treating, or gathering intelligence on the condition of the specimen population. In one aspect, a computer system is provided to assess a condition of a biological specimen by studying the physical traits of a sample that comprises a number of specimens. The condition may comprise a human central nervous system condition. A user interface is provided that comprises a computer screen, an input interface portion, and a processing mechanism. The user interface may further comprise a specimen information input mechanism. The specimen information input mechanism may comprise a specimen type input that allows the user to specify, through the computer screen input, the type of specimen to be studied.

Abstract: The invention relates to peptide mimetics of cytokine molecules that comprise an atypical helix-turn-helix motif that has been mutated to incorporate one or more amino acid residues from the active site of said cytokine molecule. In particular, the invention relates to peptide mimetics of type I cytokine molecules such as interleukin 4, (IL-4), human growth hormone (HGH) and interleukin 2 (IL-2).

Abstract: The design of antagonists of 4-helix bundle cytokine specific receptors, mimetic peptides that are able to act as such antagonists and their use as pharmaceutical agents is disclosed.

Abstract: The present invention rapidly and efficiently provides proteins engineered to bind to arbitrary target proteins requiring only knowledge of the amino acid sequences of short portions of the target proteins (for example, either the amino or the carboxy termini). This invention provides such proteins as well as methods and systems for their design, synthesis and use, and especially provides for use of a plurality of binding proteins in array format. The engineering methods of the present invention take a precursor protein known to already bind to a short peptide and engineer alterations in precursor proteins so that it binds to a new target peptide by using computer-assisted molecular design techniques and optional assay for actual binding. The invention also provides arrays and libraries of binding proteins and methods of using binding proteins.

Abstract: The present invention relates to a system and method for engineering and designing a macromolecule. An experimentally determined or de novo atomic structure that corresponds to the macromolecule is identified. The atomic structure is composed of building blocks. When the macromolecule is a peptide or a protein, the building blocks are amino acid residues. A target subset of the building blocks in the atomic structure to be optimized is identified. The coordinates of those building blocks that are not in the target subset are fixed. For each building block in the target subset, a large number of potential conformers is sample d. Each conformer to be sampled is substituted into the atomic structure and tested against an energy function that includes the equivalent energy of the conformer in a reference state. Combinations of conformers that best satisfy an interaction energy function are identified.