Netherlands
Netherlands

Pepscan is a procedure for mapping and characterizing epitopes involving the synthesis of overlapping peptides and analysis of the peptides in enzyme-linked immunosorbent assays . The method is based on combinatorial chemistry and was pioneered by Mario Geysen and coworkers. Wikipedia.

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Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.52M | Year: 2015

BIOGEL is set up to educate young scientists to develop innovative hydrogel chemistries and systems for biomedical applications. The first objective is to provide a platform for young researchers to undergo a well-rounded PhD education, particularly focussed on translational skills for a career focused in biomedical research and medical technology development. The second objective is to engineer functional and responsive hydrogels, which resemble specific properties of the extracellular matrix. The third objective is (i) to enhance the efficacy of medical devices by 2D biointegrative coatings that direct and orchestrate the interface to living cells and tissue and enable improved integration within the body, (ii) to advance therapeutic measures by 3D templates for tissue repair, and (iii) to enable new diagnostic tools by responsive diagnostic hydrogels. BIOGEL follows an international, interdisciplinary, and intersectoral approach organized in 9 and 8 interwoven work and training packages respectively. The training and research parts are focused on synthetic and biohybrid macromolecules to build clinically translatable hydrogels with specific, application directed bioactivities. In order to enable efficient biohybridisation and minimal invasive application, emphasis is set on in situ gelation of precursors that do not affect the viability of cells and living tissue and that can interlink bioactive subunits to stimulate tissue regeneration, and serve as a functional component in biomedical devices. Structural incorporation of such units must be flexible, dynamic, and responsive to stimuli. This is directed to enhance cell behavior and receptor interaction, tailor the mechanical properties, and enable spatial, temporal, and topographical control of functional components. Translational aspects focus on coatings of medical devices, diagnostic hydrogels, cartilage and bone repair, tissue engineering for cardiovascular implants, and nerve regeneration.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-7 | Award Amount: 6.29M | Year: 2008

At present more than 5 million people in the EU suffer from dementia and other neurodegenerative diseases and that number will grow as the average age of the population continues to increase. The efficacy of current medicines is limited and new therapeutic targets are sorely needed. Several independent lines of evidence have established an important role of prolyl oligopeptidase (PREP) in brain function and dysfunction. Aberrant PREP activity is involved in the progression of neurodegenerative disorders and PREP inhibitors are being developed for the treatment of memory and cognition deficits. Now a consortium of expert scientists from 8 academic institutes and 3 SMEs come together for 4 years in this NEUROPRO project to boost European research aimed at 1) unravelling the biological role of PREP and PREP-like proteins in neuropathology, 2) determining the mode of action of PREP inhibitors and 3) firmly establishing their therapeutic potential. Specialists from different disciplines cell and molecular biology, enzymology, chemistry, crystallography, biology and pharmacology will work in a concerted and focussed way to achieve the goals using 6 work packages concentrating on PREP-regulated pathways in health and disease, PREP substrates, inhibitor target identification, drug development and validation, and generation of specific cell lines and animal models of neurodegenerative diseases. The SMEs involved are leaders in PREP inhibitor development and peptide analysis, and have in the past already brought novel therapeutics on the market. By the end of the project we expect to have proof of concept that PREP inhibition is a valid therapeutic target which will ultimately lead to new methods for the early detection, prevention or restoration of PREP-related neurodegeneration. The project also comprises instruments to translate basic research into clinical applications and will thus broaden the scope of treatments available to Europes ageing population.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP-2007-1.1-1 | Award Amount: 4.94M | Year: 2008

The cause of diseases is often unknown, but their origin can frequently be found at the biomolecular and cellular level situated on nm-scale. Early diagnostics combined with early intervention on that nanoscale is one of the holy grail of modern medicine. Inorganic nanoparticles are very promising agents in that respect. One of the promising biomedical applications of these nanoparticles is their use as agents for tumor hyperthermia. Hyperthermia is a form of cancer treatment that uses an elevated temperature to kill the tumor tissue. Compared to the more conventional surgical procedures, it is hailed as a less invasive approach that could be used for small, non-defined tumors. Well-designed instrumentation in combination with engineered inorganic nanoparticles that (a) possess the desired physical properties to generate a local heat and that (b) can specifically target the tumor offer immense potentials for targeted hyperthermia therapy. The overall objective of the present multi-disciplinary project is to develop and to explore various metal/magnetic nanoparticles as agents for targeted tumor therapy. To strive for this overall objective, a successful integration and convergence of different technologies at the nanoscale is indispensable. In this project, we will focus on the synthesis routes of tailor designed biofunctionalized nanoparticles for hyperthermia. This requires a profound physical and chemical characterization of the synthesized nanostructures, but the project is certainly not limited hereto. It will also include a toxicological and biological evaluation of the different nanoparticles. Hereby a detailed exploration and characterization of the interaction mechanism of the biological entities and the nanostructures will be pursued to obtain a better understanding of the phenomena occurring at the nanoscale. In addition, this project also comprises the design of advanced instrumentation that can be used for a controlled hyperthermia treatment.


Grant
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.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.5-3 | Award Amount: 3.90M | Year: 2008

The balance between bone resorption and bone formation determines the mass and structural integrity of the skeleton and is disturbed in osteoporosis. In contrast to the molecular mechanisms regulating bone resorption, knowledge of the mechanisms regulating bone formation is limited. A recent breakthrough has been the identification of a link between bone mass in humans with rare bone disorders and gain- or loss-of function mutations of the Wnt co-receptor LRP5 or the Wnt antagonist sclerostin. The mechanism, however, underlying these actions on Wnt signalling is unclear. We propose studies with the following specific aims: i) to characterize the clinical, bioschemical, radiological and histological features of patients with sclerosteosis, van Buchem disease and other craniotubular hyperostoses ii) to determine the genetic defect in patients with craniotubular hyperostoses and establish putative genotype-phenotype correlations iii) to unravel the molecular mechanism of the inhibitory action of sclerostin on bone formation and to determine how genetic variations in SOST, LRP5 and Wnt signalling pathway modify bone architecture and remodelling iv) to reveal the pattern of sclerostin expression by analysis of the SOST promoter and by histomorphometry of human bone biopsies v) to identify and characterize co-factors of the LRP5 signalling and their in vivo actions in relevant animal models vi) to identify epitopes in sclerostin that mediate the interaction with LRP5, raise peptide-bound protein mimics and test them in vitro and in animal models of bone loss. These studies will not only help understanding the molecular basis of critical signalling pathway in bone formation but will also provide insight into normal and disturbed modulation of bone remodelling. Moreover, they will help in the design of bone forming interventions for the treatment of patients with osteoporosis.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016

We hypothesize that inappropriate thyroid hormone action in target cells is a common mechanism underlying susceptibility to age-related degenerative diseases and co-morbidities. Although regulation of systemic thyroid status is well understood and underpins treatment of common thyroid disease, it is only in the last decade that the importance of local regulation of thyroid hormone action in tissue development, homeostasis and repair has been identified. During evolution, this complex temporal and cell-specific regulation has been optimized for development and reproductive fitness but NOT for ageing. Humans with their exceptional longevity are thus exposed to a prolonged period of suboptimal local thyroid hormone action. Consistent with this, thyroid status is a continuous variable within the population that is related to fracture risk, muscle mass and cognitive decline. Moreover, in healthy longevity thyroid status is characterized by thyroid stimulating hormone in the upper half of the reference range. In these studies, we will determine how local regulation of thyroid hormone action controls tissue homeostasis and repair, whilst its dysregulation is a common mechanism underlying chronic disease development during ageing. We focus on osteoporosis, osteoarthritis, neurodegeneration and sarcopenia as paradigm age-related, degenerative disorders. Using cutting-edge technology, we will (i) identify thyroid hormone dependent biomarkers for disease susceptibility in bone, cartilage, central nervous system and skeletal muscle, (ii) manipulate cell-specific thyroid hormone action in these tissues and (iii) develop cell-type specific modulators of thyroid hormone action. THYRAGE integrates cross-disciplinary expertise from clinical and basic scientists, endocrinologists, neuroscientists, gerontologists, and industry-based peptide scientists. These studies will identify and validate novel strategies for prevention and treatment of chronic age-related degenerative disease.


Patent
Janssen R&D Ltd and Pepscan | Date: 2012-12-18

The present invention concerns an inhibitor of Human Immunodeficiency Virus (HIV) fusion with, or HIV entry in, a host cell comprising at least 24, but preferably 26, contiguous amino acids; the invention also relates to a pharmaceutical composition comprising said amino acids.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.8.3 | Award Amount: 4.24M | Year: 2008

In the BRAINSTORM project, we aim to develop an integrated system enabling on-chip intracellular recordings from a relatively large cultured neuronal network combined with chemical sensing and intracellular delivery of biologically active molecules. To achieve tight coupling with the cell membrane and enable efficient recordings, micronail-type probes will be integrated with a CMOS readout circuitry. These micronails are structured to operate either as intracellular microelectrodes or as intracellular micro-syringes allowing either chemical injection or to produce pressure or suction that will be used in additional to other procedures to penetrate the cell membrane. With appropriate bio-functionalization, the micro-nails inserted intracellularly will also serve as sensors for phosphorylation/ dephosphorylation reactions within living cells.\nThe main technologies and methods to be developed in the BRAINSTORM project include:\n\tBiocompatible and CMOS compatible micronails and micro-syringes with integrated readout electronics;\n\tMicrofluidic system integrated with the CMOS-containing chip;\n\tProcedures to insert both nail types through the plasma membrane, into the neuronal cytosole;\n\tSurface chemistries allowing to achieve a Giga-Ohm (G) seal resistance between the disrupted plasma membrane and the nail;\n\tHigh signal-to-noise ratio recordings of neuronal electrical activity with micronail probes;\n\tOn-chip chemical delivery of chemicals;\n\tOn-chip sensing of intracellular kinase activities.


Patent
Pepscan | Date: 2014-03-07

The disclosure relates to the field of candidate drug testing and drug development. A method is provided for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule capable of reacting with the at least first and second reactive group; contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the at least one molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage, preferably wherein the coupling reaction is performed in solution, more preferably in an aqueous solution. Furthermore, a method is provided for selecting a candidate drug compound comprising providing a library of compounds hereof and determining the binding of a target molecule to the compounds.


Patent
Pepscan | Date: 2014-03-07

The disclosure relates to the field of candidate drug testing and drug development. Described are methods for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule able to react with the at least first and second reactive group; and contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage. The coupling reaction may be performed in solution, such as an aqueous solution. Furthermore, described is a method for selecting a candidate drug compound comprising providing a library of the compounds and determining the binding of a target molecule to the compounds.

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