Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.1-1 | Award Amount: 5.55M | Year: 2012
We want to further develop our tools and technologies for high-throughput research, with the final goals being (I.) the particle-based combinatorial synthesis of 1 Mio different peptides on a glass slide for chemical costs of ~50 (KIT, CBL, MS, TUV), and (II.) the labelling-free parallel readout of binding affinities by a variant reflectometric interference spectroscopy method for ~10.000 peptide spots per cm(\2) when staining the array with an unlabeled protein (BIA, KIT). These tools provide the basis (III.) for a standardized, fast, and reliable high-throughput procedure that we want to develop in order to find high-affinity peptide binders against any pharmaceutically interesting target protein. Such a procedure might have an important impact in medicine and in the biotechnology industry. In order to achieve this goal, we will use display techniques that in combination with high-throughput sequencing typically will identify ~100.000 putative peptide binders per target protein (ISO). These will be synthesized in array format to validate binding to the target protein by an independent method (PPP, DKFZ). Next, based on binders from initial screens, many variant peptides are synthesized in high-density array format for iterative screens (PPP, DKFZ, KIT), whereby massive parallel labelling-free detection of binders pinpoints higher-affinity binders (BIA). In order to validate our novel high-throughput procedure, (IV.) we want to find high-affinity peptide binders against relevant target proteins (delivered by APO and OXF), and test these binders in biological assays (OXF, APO).
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 4.00M | Year: 2013
The ITN WntsApp is organized to achieve 3 key aims: (i) Provide a committed training programme for young researchers to bridge the gap between basic scientific knowledge and drug development, (ii) Centring research on a key cancer-signalling pathway, WNT signalling, to stimulate synergies and (iii) Strengthening the link between international partners and private enterprises to stimulate innovation and facilitate exploitation of results. We have recruited ten full partners from academia and industry from seven EU countries, providing a highly interactive research and training programme. Fellows get exposed to a wide range of activities in the private sector, including biotechnology and drug development, but also the publishing business. WntsApp fellows also profit from the activities of the SME PCDI, who are professionals in advising and supporting young graduates researchers. The scientific focus will be on the WNT signalling pathway that mediates critical cell fate decisions and is strongly linked to cancer. The fellows will address the mechanisms that relay cellular WNT signals from the membrane to the cytosol and nucleus, at the atomic, molecular and organismal level. The underlying molecular mechanisms provide attractive drug targets, particularly in regenerative medicine and cancer treatment. We will study and interfere with WNT signalling at various levels, focusing on conceptual advances regarding receptor specificity, allosteric effects, assembly and disassembly of complexes, WNT-regulated conformational changes, regulation of protein stability, role of molecular chaperones, protein-protein interactions, consequences for stem cell maintenance, mutation-induced tumourigenesis and the generation of high affinity agonists and antagonists that modulate receptor activity. The coherent class of students working on this multidisciplinary theme will create synergisms, stimulate associated graduate schools and offer new opportunities for exploitation of results.
Ullman C.G.,Isogenica |
Frigotto L.,University of Oxford |
Briefings in Functional Genomics | Year: 2011
The presentation of recombinant peptide libraries linked to their coding sequence can be referred to as 'peptide display'. Phage display is the most widely practiced peptide display technology but more recent alternatives such as CIS display, ribosome display and mRNA display offer advantages over phage for speed, library size and the display of unnatural amino acids. These have provided researchers with tools to address some of the failings of peptides such as their low affinity, low stability and inability to cross biological membranes. In this review, we assess some of the recent advances in peptide display and its application. © The Author 2011. Published by Oxford University Press. All rights reserved.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 141.32K | Year: 2014
The ability to assemble genes from smaller DNA fragments or generate combinatorial libraries of genetic mutations is fundamental to the field of synthetic biology. Different methodologies exist for their fabrication but enzymatic assembly produces a consistently high quality product, compared to other methods, which is essential for downstream processes for improved characteristics such as improved strains or improved protein function/yield. The project aims to achieve combinatorial gene assembly in a high throughput, automatable fashion, delivering a powerful and valuable tool for commercialisation in the synthetic biology arena and providing potential benefits for drug discovery and industrial applications.
Isogenica | Date: 2011-11-09
The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein: DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.
Isogenica | Date: 2013-03-15
A method is disclosed for identifying a member of a peptide library that interacts with a target molecule in situ, the method including expressing immobilised nucleic acid molecules to produce the peptide library in a way that each member of the peptide library is immobilised on the nucleic acid molecule from which it was expressed; contacting the immobilised peptide library with the target molecule; and detecting an interaction between at least one member of the peptide library and the target molecule. The method further comprises sequencing the plurality of nucleic acid molecules in situ on the solid support, such that the at least one member of the peptide library that interacts with the target molecule can be immediately identified, at least by the sequence of the nucleic acid molecule from which it was expressed, without requiring additional or secondary analysis or characterising procedures in order to identify the useful members of the library. The target molecules may themselves be comprised within a second nucleic acid or peptide library.
Isogenica | Date: 2010-10-21
The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein:DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.
Isogenica | Date: 2011-01-11
A method is provided for isolating protease resistant antimicrobial peptides (AMPs) from a peptide display library. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of peptide-nucleic acid complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide. The complexes are exposed to at least one protease, to allow the proteolysis of protease-sensitive peptides, such that resistant peptides remain. The peptide-nucleic acid complexes are further exposed to a membrane composition to allow association of complexes that contain membrane-associating peptides. Complexes that remain unassociated with the membrane are removed; and membrane-associated complexes are recovered. The AMPs so characterised may be resistant to one or more protease enzymes and exhibit antimicrobial activity against one or more microbe.
Isogenica | Date: 2011-08-08
A naive WW domain peptide library derived from a WW domain peptide sequence which has been diversified by changing the amino acid sequence at one or more positions is provided. The naive WW domain peptide library may be derived from a GroupIV WW domain peptide. Methods for making the naive WW domain peptide library and methods for selected a modified WW domain peptide that binds a target ligand using the naive WW domain peptide library are also provided. Also disclosed are modified WW domain peptides that bind desired target ligands, pharmaceutical compositions comprising such peptides, and uses for such peptides. The modified WW domain peptides have altered, improved or different, target ligand binding characteristics to those of the unmodified WW domain peptides from which they are derived.
News Article | February 21, 2017
CAMBRIDGE, England--(BUSINESS WIRE)--Isogenica Ltd, a leader in the design and construction of innovative and highly diverse synthetic antibody libraries, today announced a new licensing deal with a top-25 global pharmaceutical company which specialises in immunology, oncology and immuno-oncology biopharmaceuticals. Under the terms of the agreement, Isogenica has granted its licensee licences to its family of llamdA™ VHH single-domain antibody libraries for the discovery, development and commercialisation of therapeutic products derived from these libraries. Isogenica is entitled to an upfront and annual licence payments. If antibodies are advanced into development, Isogenica is entitled to further commercial upfront, licence and downstream payments. Adam Collier, Isogenica’s Director of Commercial Development commented: “This is a very significant deal for Isogenica, which further validates and endorses the company’s highly diverse family of synthetic camelid single-domain antibody (VHH) libraries as an excellent starting point for therapeutic antibody discovery. We look forward to enabling existing and new partners to find novel, developable therapeutic candidates quickly and efficiently”. Isogenica is a synthetic biology company focusing on the design and build of diverse antibody libraries for use in biopharmaceuticals. Partners can access an advanced camelid single-domain antibody library (llamdA™) and state-of-the-art, fully synthetic and highly diverse human antibody libraries. The company uses its proprietary Colibra™ library technology to ensure that the constructs very accurately reflect its advanced library designs. Libraries can be screened in various formats, including phage and CIS-Display, a proprietary in vitro display technology which maintains the high diversity of the llamdA™ libraries through the discovery process. Isogenica licenses advanced synthetic antibody libraries and display technologies to enable its partners’ antibodies discovery activities. These libraries are available for license and screening partnerships, which together with its expertise in the screening of displayed peptide and scaffold libraries, can facilitate client’s biologics discovery needs. www.isogenica.com