Electrical heart disease leading to arrhythmias represents a major public health issue because it increases the risk for sudden cardiac death. The EUTrigTreat project investigates arrhythmia initiating mechanisms (Triggers) and addresses therapeutic strategies (Treatments) through translational and interdisciplinary strategies. The multidisciplinary research team of this large-scale collaborative excellence project set out to elucidate molecular and environmental mechanisms which underlie life-threatening cardiac arrhythmias, and how genes and external factors modulate and initiate catastrophic electrical abnormalities in the heart.
PolyGene’s role in EUTrigTreat was to generate more than 20 mouse models for various collaborating groups, and to build a cardiac-specific inducible knockout system to regulate one of those genes. All models were delivered in time to specification, in early phases of the project, to accommodate downstream research in our partner groups within the narrow time frame of EUTrigTreat. Official Webpage
The overall aim of CAM-PaC is to use a strongly SME-driven approach to contribute to solving the socioeconomic and health challenges of pancreatic ductal adenocarcinoma by an integrative and systematic functional analysis of pancreatic cancer candidate genes pre-selected and pre-characterised by members of the consortium in previous and ongoing HT-omics approaches.
CAM-PaC develops novel cellular and animal models for this aim, as well as novel strategies to analyse and integrate large scale metabolic, transcriptomic and genetic data. CAM-PaC systematically identifies, characterises and validates novel targets for therapeutic intervention and bioinfomatic models for predictive diagnostics.
PolyGene’s role is to supply these models (close to 20 novel mouse models), and on the other hand, to develop novel tools for gene expression regulation based on the antibiotic-driven expression systems currently already available at PolyGene, and patent protect them. Official Webpage
The focus of the TumAdoR consortium is the development of human therapeutic monoclonal antibodies efficiently neutralizing a novel immunosuppressive pathway involved in a wide range of cancers. The project is based on studies that demonstrated a causative correlation of overexpression of CD73 with tumor proliferation and dissemination in numerous cancer types, by catalyzing high levels of extracellular Adenosine and thereby causing a immunosuppressive microenvironment. TumAdoR will extend the knowledge on this key pathway in cancer research. Neutralizing CD73 by developing clinically validated CD73 monoclonal antibodies represents a highly potent and innovative therapy.
PolyGene is generating a mouse model that uses an advanced and novel approach for the inducible humanization of CD73. Official Webpage
Skeletal diseases range from a large and diverse group of rare monogenic diseases (such as chondrodysplasias) to highly prevalent but genetically complex diseases such as osteoarthritis (OA) and osteoporosis (OP). The overall concept of this FP7-funded project is to study the genetic causes of both rare and common skeletal diseases in order to gain a better understanding of the disease processes and age-related changes and to deliver new and validated therapeutic targets. SYBIL brings together a complementary translational and transnational group of world-class scientists, systems biologists, disease modellers, information technologists and industrialists that will achieve critical mass to deliver the ambitious objectives of this programme of research.
PolyGene has already delivered half of the 16 animal model projects undertaken for its partners in the consortium. Now we are working on the remaining projects in order to ship the mice well ahead of schedule.
This poster was kindly provided by Timur Yorgan (SYBIL, University Medical Center Hamburg Eppendorf). Official Webpage
Identification and validation of novel pharmaceutical drug targets for cardiovascular disease (since 2013)
Cardiovascular disease (CVD), including high blood pressure, coronary artery disease, heart disease and stroke, is the leading cause of death in the world. To improve the life-expectancy of CVD patients, the multi-partner, FP7-funded consortium CarTarDis (Cardiovascular Target Discovery) set out to advance the development of CVD medicines by discovery and validation of novel therapeutics targets to CVD.
PolyGene plays an important role by supplying partners with target validation models of both, already defined novel target genes, and additional targets emerging in the ongoing consortiums’ screenings; on the other hand, PolyGene is able to improve its competitive position by establishing heart-specific gene regulation systems based on our exclusive tools of hormone and antibiotic regulation. Official Webpage
8 years ago we made a knockout mouse unraveling the function of a calcium-binding protein (Calsequestrin) in the heart muscle. Finally it is published!
Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ventricular tachycardia. By using a CSQ2 knockout mouse we wanted to study also the atrial function of CSQ2.
These data suggest a functional role of CSQ2 not only in the ventricle but also in the atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias, but also cardiac hypertrophy and heart failure.
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Link to the publication: http://onlinelibrary.wiley.com/doi/10.1111/apha.12766/full