Project acronym BTVI
Project First Biodegradable Biocatalytic VascularTherapeutic Implants
Researcher (PI) Alexander Zelikin
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), PE8, ERC-2013-CoG
Summary "We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Summary
"We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Max ERC Funding
1 996 126 €
Duration
Start date: 2014-04-01, End date: 2019-09-30
Project acronym miPDesign
Project Designing microProteins to alter growth processes in crop plants
Researcher (PI) Stephan Wenkel
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS9, ERC-2013-StG
Summary The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Summary
The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Max ERC Funding
1 443 320 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
