Abstract: The invention relates to a complexing system comprising two polypeptide helices derived from a SNAP protein; one polypeptide helix derived from syntaxin; one polypeptide helix derived from synaptobrevin or a homolog thereof; and one or more cargo moieties attached to the polypeptide helices, wherein the four polypeptide helices can form a stable SNARE complex. The invention also relates to a method of producing the complexing system and the use of the complexing system.

Abstract: Orthogonal ribosome orthogonal mRNA pairs are provided, as are methods for their selection involving a novel positive-negative selection approach, and methods for their use. Also provided are cellular logic circuits involving orthogonal ribosomes.

Abstract: The invention relates to a tRNA synthetase capable of binding N?-acetyl lysine, in particular, the invention relates to a tRNA synthetase capable of binding N?-acetyl lysine wherein said synthetase comprises a polypeptide having at least 90% sequence identity to the amino acid sequence of MbPy1RS. The invention also relates to a method of making a polypeptide comprising N?-acetyl lysine comprising arranging for the translation of a RNA encoding said polypeptide, wherein said RNA comprises an amber codon, wherein said translation is carried out in the presence of a polypeptide according to any of claims 1 to 11 and in the presence of tRNA capable of being charged with N?-acetyl lysine, and in the presence of N?-acetyl lysine.

Abstract: The present invention relates to variants of the NK1 fragment of the polypeptide growth factor HGF/SF which act as agonists of the MET receptor and their use. The agonists comprise at least one substitution at positions equivalent to 132, 134, 170 and 181 of full length HGF/SF and these substitutions provide a variant which shows scatter factor activity and induces DNA synthesis. In vivo the variants provide protection from liver damage in a model of acute liver failure.

Abstract: The present invention relates to a method for isolating from the immunological gene repertoire a gene coding for a receptor having the ability to bind a preselected ligand. Receptors produced by the gene isolated by the method, particularly catalytic receptors, are also contemplated.

Abstract: A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA.

Abstract: A compound of formula I, or a pharmaceutically acceptable salt or ester thereof, wherein R1 is selected from: aryl; heteroaryl; —NHR3; fused aryl-C4-7-heterocycloalkyl; —CONR4R5; —NHCOR6; —C3-7-cycloalkyl; —O—C3-7-cycloalkyl; —NR3R6; and optionally substituted —C1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C4-7-heterocycloalkyl and C4-7-heterocycloalkyl are each optionally substituted; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl, heteroaryl, C4-7 heterocycloalkyl and halogen, wherein said C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl and C4-7-heterocycloalkyl are each optionally substituted; R3 is selected from aryl, heteroaryl, C4-7-heterocycloalkyl, C3-7-cycloalkyl, fused aryl-C4-7-heterocycloalkyl and C1-6-alkyl, each of which is optionally substituted; R4 and R5 are each independently hydrogen, or optionally substituted C3-7-cycloalkyl, aryl, heteroaryl, C1-6-alkyl or C3-6-heterocycloalkyl; or R4 and R5 together with the N to which they are attached form a C3-6-h

Abstract: The present invention provides for isolated polynucleotides encoding a human 3-phosphoinositide-dependent protein kinase, and vectors and host cells comprising the isolated polynucleotides.

Abstract: The present invention identifies that the expression of Activation Induced Deaminase (AID) or its homologues in cells confers a mutator phenotype and thus provides a method for generating diversity in a gene or gene product as well as cell lines capable of generating diversity in defined gene products. The invention also provides methods of modulating a mutator phenotype by modulating AID expression or activity.

Abstract: The invention relates to novel NO donors which are targeted to the mitochondria. The NO donor compounds of the invention allow NO to be selectively provided to the mitochondria.

Abstract: The invention relates to a method of detecting a structural change in a molecule, said molecule being attached to a surface, said surface being electrically conductive, wherein the phase of the electrochemical impedance at said surface is monitored, and wherein a change in the phase in the electrochemical impedance at said surface indicates a change in the structure of said molecule. The invention further relates to methods for making arrays having molecules such as, polypeptides attached to electrically conductive surfaces such as electrodes, and to arrays.

Abstract: Disclosed is a bubble excluder device (2) adapted for use with, and attachment to, a probe (6) for continuous measurement of the cell density of a culture in a liquid medium; the bubble excluder device comprising an inlet and an outlet to allow flow of liquid through the device and bubble exclusion means (20) to reduce or prevent ingress of bubbles from the liquid medium outside the device.

Abstract: Variants of the NK1 fragment of the polypeptide growth factor HGF/SF which act as agonists of the MET receptor and their use are disclosed. The agonists comprise at least one substitution at positions equivalent to 132, 134, 170 and 181 of full length HGF/SF (SEQ ID NO:2) and these substitutions provide variants which show scatter factor activity and induce DNA synthesis. In vivo, the variants provide protection from liver damage in a model of acute liver failure.

Abstract: A method for selecting a compound for modulating the activity of phosphoinositide dependent protein kinase 1 (PDKI) is provided. The method may comprise modelling a three dimensional structure of a plurality of molecules in a computer, comparing with the three dimensional structure of the compounds with that of a reference structure such as at least part of a protein kinase catalytic domain of PDK1, and selecting the compound based on a predicted interacting ability of the molecules to the protein kinase catalytic domain. Also a method for selecting a compound for modulating the activity of hydrophobic pocket containing protein kinase is provided. In this method, the reference structures may be one or more of a phosphate binding pocket of PDK1, a hydrophobic pocket of PDK1, and ?C helix or region interacting therewith of PDK1.

Abstract: Methods for use in the synthesis and identification of molecules which bind to a target component of a biological system or modulate the activity of a target are described.

Abstract: The invention relates to a method of detecting an altered behaviour in a population of cells, said method comprising determining at least one of the following characteristics of the population of cells; (i) the proportion of stem cells, proliferating cells and differentiated cells in said cell population; or (ii) the size of stem cell clusters in said cell population; or (iii) the separation of stem cell clusters in said cell population; and comparing said at least one characteristic to a reference value, wherein a difference between the determined value and the reference value indicates an altered behaviour in said population of cells. Preferably the cells are mammalian, more preferably human epithelial cells, more preferably human epidermal cells.

Abstract: The present invention relates to the development of a novel method for the selection of nucleic acid processing and other enzymes. In particular the invention relates to a method for the selection of nucleic acid polymerases and other enzymes with desired properties based on the method of compartmentalized self-tagging.

Abstract: The invention relates to a method of identifying a modulator of RHBDL4, said method comprising (i) providing a first and second sample of cells; (ii) contacting said first sample of cells with a candidate modulator of RHBDL4; (iii) measuring epidermal growth factor receptor (EGFR) transactivation in said first and second samples of cells, wherein a difference between the transactivation measured in said first and second samples of cells identifies said candidate modulator of RHBDL4 as a modulator of RHBDL4. The invention also relates to RHBDL4 protease assays and to uses of RHBDL4 protease and methods of cleavage of RHBDL4 substrates.

Abstract: The invention relates a fragment derived from the MET ectodomain which the inventors have found is capable, in monomer form, of binding to HGF/SF either in the presence or absence of heparin. The availability of soluble, monomeric forms of the MET receptor enabled studies of its solution properties and HGF/SF binding and provides an assay comprising the steps of (a) providing a MET ectodomain fragment; (b) providing an agent; and (c) determining the extent to which the agent interacts with said fragment.