Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-30-2015 | Award Amount: 5.01M | Year: 2016
SMARTool aims at developing a platform based on cloud technology, for the management of patients with coronary artery disease (CAD) by standardizing and integrating heterogeneous health data, including those from key enabling technologies. The platform includes existing multiscale and multilevel ARTreat (FP7-224297) models of coronary plaque progression based on non-invasive coronary CT angiography (CCTA) and fractional flow reserve computation, refined by heterogeneous patient-specific non-imaging data (history, lifestyle, exposome, biohumoral data, genotyping) and cellular/molecular markers derivable from a microfluidic device for on-chip blood analysis. SMARTool models will be applied and validated by historical and newly acquired CCTA imaging plus non-imaging health data from the EVINCI project (FP7-222915) population. SMARTool cloud-based platform, through Human Computer Interaction techniques, 3D visual representation and artery models, will use heterogeneous data in a standardized format as input, providing as output a CDSS - assisted by a microfluidic device as a point of care testing of inflammatory markers for: i) Patient specific CAD stratification - existing models, based on clinical risk factors, will be implemented by patient genotyping and phenotyping to stratify patients with non-obstructive CAD, obstructive CAD and those without CAD, ii) site specific plaque progression prediction - existing multiscale and multilevel ARTreat tools of CAD progression prediction will be refined by genotyping and phenotyping parameters and tested by baseline and follow CCTA and integrated by non-imaging patient-specific data, iii) patient-specific CAD diagnosis and treatment - life style changes, standard or high intensity medical therapy and a virtual angioplasty tool to provide the optimal stent type(s) and site(s) for appropriate deployment.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 15.78M | Year: 2013
The aim of SYBIL is to carry out extensive functional validation of the genetic determinants of rare and common skeletal diseases and the age related factors contributing to these painful conditions. To achieve this goal SYBIL will gather complementary translational and transnational scientists, systems biologists, disease modellers, leading SMEs and industrialists that will perform in-depth characterisation (complete molecular phenotyping) of pre-clinical models (cellular and animal) for a variety of common and rare skeletal diseases. SYBIL will establish a systematic pipeline of in vitro, ex vivo and in vivo models of increasing complexity and will also make use of novel technologies such as iPS cells and exclusive Virtual Patient software to identify potential therapeutic targets for further validation through simultaneous modelling of fundamental and complex physiological pathways. SYBIL will rely on i) an Omics Knowledge Factory for systematically generating new knowledge on skeletal disease pathophysiology and to generate the relevant Omics profiles necessary to detect and validate new disease determinants, biomarkers and therapeutic targets for future clinical developments, and ii) a Systems Biology Hub to integrate the high-throughput and data-dense information, to gain a global understanding of pathophysiological commonalities between different skeletal diseases and recognize predominant shared pathways and mechanisms that may represent new targeted routes to treatment. SYBIL will also identify potential modifier genes and study the epigenome that will ultimately influence the timing and efficacy of new personalised treatments. Overall SYBIL achievements will tremendously boost the efficient pre-clinical assessment and development of therapeutics against skeletal diseases and thus indirectly reduce their social and healthcare burden.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 2.91M | Year: 2016
The advent of analytical techniques with extremely low limits of detection has led to dramatic progresses mostly in the field of nucleic acids sequencing. Despite the advent of the next generation sequencing platforms, the current genome sequencing task remains formidable, and revolutionary advances in DNA sequencing technology are still demanded. Nevertheless, the primary actors in virtually all life processes are the proteins coded by DNA sequences known as genes. Proteins can yield far more compelling revelations than may be gleaned from DNA alone. Protein sequencing may radically transform patient treatment, enabling precise monitoring of disease response to therapeutics at the molecular level. Single-molecule sequencing of proteins is of enormous value, offering the potential to detect diminishingly small quantities of proteins that may have been altered by alternative splicing or post-translational modification. In this project, we build upon current state-of-the-art sequencing technologies to develop novel proof-of-principle technologies for high-throughput protein sequencing and single molecule DNA/RNA sequencing. The work proposed herein will provide: (i) a new sequencing technology development that utilizes plasmonic nanostructures in order to enhance the optical detection and to control the molecules movement by means of optical trapping; (ii) a novel approach of plasmonic based optical spectroscopy for sequencing of protein; (iii), a rigorous analytical model to reconstruct the exact sequence from the signals recorded; and (iv) a plasmonic device that can perform both nucleic acids and amino-acids sequencing in one functional unit. These research efforts provide a foundation for the novel use of systems for a wide range of applications, such as the framework to investigate next generation protein sequencing, as well as high-throughput DNA sequencing and genetic diagnostics.
TREGeneration - Repair of tissue and organ damage in refractory chronic graft versus host disease after hematopoietic stem cell transplantation by the infusion of purified allogeneic donor regulatory T lymphocytes
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2014 | Award Amount: 5.90M | Year: 2015
Our proposal encompasses parallel clinical trials addressing the feasibility and the effectiveness of donor-derived regulatory T cells (Treg) as a therapeutic agent in the treatment and prevention of tissue and organ damage resulting from graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). We propose a collaborative clinical study in which Treg therapy for GHVD is the common dominator. However, by bringing together several clinical centers with expertise in this area, we are also having the opportunity to simultaneously address other issues that would not otherwise be addressable by each clinical center on its own. Firstly, by using different Treg preparation strategies, we will be able to determine whether ex vivo isolated Treg are sufficient or whether in vitro expansion and subsequently higher dosages are required. Secondly, we will investigate if sole Treg infusion is effective or if rather co-administration of therapeutic agents that are likely to induce Treg survival and expansion in vivo (rapamycin; IL-2) is required for a successful response to Treg therapy. The studies on GVHD treatment outcome will be pursued together with a detailed analysis of immune monitoring, comprising T cell receptor clonotype tracking and tissue regeneration markers, in order to further understand the mechanisms underlying the therapeutic and regenerative potential of Treg cells. Our consortium has developed a concerted approach to the topic of Treg therapy in GVHD. This is a unique opportunity to determine the validity of this cellular immunotherapy approach in GVHD prevention and treatment, with potential for a significant impact on patient quality of life, survival rate and ultimately on the quality of health care provided.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BIOTEC-2-2015 | Award Amount: 10.71M | Year: 2016
Recent developments in omics technologies demand implementation of systems biology approaches to facilitate analysis and interpretation of the generated complex datasets.This is essential for biotechnological as well as preclinical and clinical applications. In comparison to previous approaches, most cancer relevant studies are confined to pattern recognition or at best modelling of single pathways, rather than the complex pathways and cross-talk determining cancer progression and drug response. Systematic tools that evaluate and validate personalised medicine approaches on a preclinical level are missing; an important prerequisite for translation into clinical practice. The overall objective of CanPathPro is to build and validate a new biotechnological application: a combined experimental and systems biology platform, which will be utilized in testing cancer signaling hypotheses in biomedical research and life sciences. Thus, the proposed project will focus on developing and refining bioinformatic and experimental tools for the evaluation of systems biology modelling predictions. Components comprise a highly controlled mouse experimental system, NGS, a quantitative proteomics based read-out of changes in pathway signalling and an integrative systems biology model for data integration. Testable hypotheses about biological systems will be generated and experimentally validated. The developed system tools will be made available to researchers, SMEs and industry for practical applications. Following this project, a commercial platform for interpretation and analysis of complex omics data and for deriving and testing new hypotheses will be set up by the participating companies and academic partners. CanPathPro will enhance the competitive potential of the SMEs involved expanding in the field of biotechnology, personalised medicine and drug development and also provide new opportunities for other SMEs working in the field of bioinformatics and biomedical applications.
Alacris Theranostics GmbH and Max Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Date: 2014-12-08
The idea of this invention is to prepare ordered oligonucleotides arrays from two or more pre-synthesized shorter partsblock-synthesis approach. The parts are linked together enzymatically to form a full-length oligonucleotide of a desired sequence. Such an approach allows splitting the oligonucleotide sequences into common and unique parts. It gives the possibility to place the functional group on a common part and to minimize the length of the unique parts. Method of the invention allows combinatorial synthesis of position-specific regions. Using combinatorial approach, position-specific regions are generated by linking two or more unique oligonucleotides, so that just few said unique oligonucleotides give rise to a large variety of codes, for example, 10 unique oligonucleotides linked pairwise can produce 100 position-specific regions. In comparison to preparation of oligonucleotide arrays by spotting of full-length sequences, suggested approach is more cost-efficient, allows flexibility in generating position-specific unique sequences and is less prone to oligonucleotide length restrictions. In comparison to in situ synthesis of oligonucleotides from nucleotides, current invention allows cost-efficient solution for synthesis of oligonucleotides with free 3 ends. Important application of the current invention is preparation of two-dimensional oligonucleotide arrays for preparation of sequencing libraries from 2D distributed NA molecules. Oligonucleotides on such arrays need to have position-specific sequences and free 3 ends for further enzymatic reactions.
Alacris Theranostics GmbH | Date: 2015-04-15
The present invention relates to a method for identifying a therapeutic drug combination against a cancer, wherein the cancer comprises at least two alterations in at least two different, but crosstalking signaling pathways, the method comprising the steps of: a) providing a kinetic model of a biological network for said cancer comprising the at least two different, but crosstalking signaling pathways, wherein the kinetic model is generated by choosing a network topology, wherein the nodes of said topology represent biological entities selected from the group comprising genes, transcripts, peptides, proteins, protein modification states, small molecules, complexes, metabolites and modifications thereof, and the edges of said topology represent interactions between said entities, assigning kinetic laws and kinetic constants to the interactions and assigning concentrations to the biological entities, such that the kinetic model reflects the genome, epi-genome, proteome and/or transcriptome of said cancer, b)selecting test combinations from a plurality of known drugs, each test combination comprising at least two drugs, c) simulating the effect of each test combination on the biological network, thereby d) identifying from said test combinations a drug combination that acts against said cancer.
Alacris Theranostics GmbH | Date: 2015-06-17
The idea of this invention is to prepare ordered oligonucleotides arrays from two or more presynthesized shorter parts - block-synthesis approach. The parts are linked together enzymatically to form a full-length oligonucleotide of a desired sequence. Such an approach allows splitting the oligonucleotide sequences into common and unique parts. It gives the possibility to place the functional group on a common part and to minimize the length of the unique parts. Method of the invention allows combinatorial synthesis of position-specific regions. Using combinatorial approach, position-specific regions are generated by linking two or more unique oligonucleotides, so that just few said unique oligonucleotides give rise to a large variety of codes, for example, 10 unique oligonucleotides linked pairwise can produce 100 position-specific regions. In comparison to preparation of oligonucleotide arrays by spotting of full-length sequences, suggested approach is more cost-efficient, allows flexibility in generating position-specific unique sequences and is less prone to oligonucleotide length restrictions. In comparison to in situ synthesis of oligonucleotides from nucleotides, current invention allows cost-efficient solution for synthesis of oligonucleotides with free 3 ends. Important application of the current invention is preparation of two-dimensional oligonucleotide arrays for preparation of sequencing libraries from 2D distributed NA molecules. Oligonucleotides on such arrays need to have position-specific sequences and free 3 ends for further enzymatic reactions.
Alacris Theranostics GmbH | Date: 2016-02-03
The present invention relates to a method of clonally sorting and isolating living cells, which have a specific ribonucleic acid (RNA) molecule in common, wherein the ribonucleic acid molecule is the transcriptional product of at least two different genomic regions, the method comprising the steps of:a. providing a sample comprising said living cells;b. providing at least one labeled probe set, each probe set comprisingi. a first probe which is specific for a region of the ribonucleic acid stemming from a first genomic region and,ii. a second probe which is specific for a region of the ribonucleic acid stemming from a second genomic region and,c. transfecting said cells with said probe set such that hybridization to said regions of the ribonucleic acid molecule may occur and if said hybridization occurs the probes lie adjacent to one another on said ribonucleic acid molecule;d. detecting hybridization of said probe set to said nucleic acid regions; ande. sorting the cells depending on how hybridization to said regions has occurred.
Alacris Theranostics GmbH | Date: 2014-02-05
The present invention relates to a method for nucleic acid amplification, and detection or sequencing, comprising the steps of,a. providing a double stranded target nucleic acid molecule for amplification,b. terminally attaching to said target nucleic acid molecule both up-stream and downstream a first and second linker nucleic acid comprising a protelomerase target sequence,c. reacting said target nucleic acid molecule with a protelomerase, preferably as encoded by SEQ ID NO. 1, such that the target nucleic acid is converted to a circular target nucleic acid,d. amplifying the circular target nucleic acid in an amplification reaction comprising a polymerase and at least one first primer which binds outside the protelomerase target sequence such that an in parts self complimentary amplification product is synthesized.