Proteins are the functional macromolecules in cells, they are the main drug targets and also used as pharmaceuticals and in biotechnology. Notably, nearly 30% of proteins in eukaryotic cells are known to be membrane proteins. Mutations or improper folding of these proteins is associated with many known diseases such heart disease, cystic fibrosis, depression, obesity, cancer and many others. Currently approximately 60% of available drugs target membrane proteins.
Although most commercial drugs result from conventional discovery methods, it is the structural information provided by three-dimensional protein structures that unveils the crucial structural arrangement and atomic interactions in drug-protein complexes. This information is critical in the rational design of new drugs with improved selectivity and pharmaceutical properties.
Prometeus will address the need to provide excellent academic groups in Europe that address protein targets dealing with relevant health and technology global issues (antibiotic design, prostatic cancer, cancer theranostics, nanotechnology, food industry, agricultural pest management and aquaculture) with training in key advanced technologies provided by SME or TC large facilities.
The cutting-edge research projects will expand the breadth and the visibility of the SMEs and constitute an integrated network for future joint research grants, in the European and global context.
DRUGS
Prometeus will deliver a global collaboration providing drug leads, “from gene to molecule”. The multidisciplinary character of this task makes efforts of most institutions insufficient to provide a research programme that excels in every aspect of the process.
Prometeus innovation character does not reside in the development of new methodologies, but in forming and interdisciplinary and intersectorial team that will deal with challenging novel targets with a remarkable critical mass, achieving the identification of innovative drug leads and theranostics tools.
The consortium consists of 9 beneficiaries and 2 partners (7 academic and 4 SME) Members are from 4 EU countries, plus the USA. Prometeus will consolidate the partnership among institutions with joint research activities in the following Methodological Domains of protein production and characterization and drug design:
- High-throughput cloning and expression of both prokaryotic and eukaryotic targets.
- High-throughput detergent screening and optimization.
- Assays of protein function.
- Structure determination.
- Virtual screening of ligands and inhibitors
- Design and synthesis of ligands and inhibitors/new drug leads
- Activity, delivery and toxicity assays in cell lines
- Training in complementary skills related to patenting and partnerships.
We have a common denominator in the focus on membrane proteins, which demand a set of unique and specialized technologies, that few Academic Institutions and only big Pharma can afford. With Prometeus we are creating a network that will allow the pooling of expertise and resources in crucial enabling methodological domains.
We identify the following Strategic Biomedical Domains and a list of relevant membrane protein targets, which are the subject of research projects in the partner institutions
- Oncology.
- Signalling (hormones and GPCR odorant receptors).
- Targets for antimicrobial agents (antibiotic).
- Complexes of modified ferritins with their membrane receptors (theranostics).
TARGETS
TARGETS from ITQB (Instituto de Tecnologia Quimica e Biologica)
Arabinofuranosyltransferases AftaA-D and arabinosyltransferases EmbA-D. CDP-alcohol phosphotransferases that participate in the biosynthesis of phospholipids (required for microbial pathogenesis).
TARGETS from Sapienza (Sapienza, Università di Roma)
Membrane embedded enzymes involved in prostatic hyperplasia and cancer (steroid 5-alpha reductases) and in rare congenital neurological disorders (trans enoyl CoA reductase, polyprenol reductase). Potential target in psychiatric disorders, given their pivotal involvement in neuro-steroid production.
TARGETS from UNIVPM (Università Politecnica delle Marche)
Membrane olfactory receptors (ORs) involved in perception of volatile and non-volatile odorants (chemicals and molecules) by vertebrate. As they belong to the G-protein coupled receptor (GPCR) family, the production of these proteins for structural studies is very challenging and critical to understand functions and/or dysfunctions and to perform the rational design of selective agonists or antagonists.
TARGETS from Molirom
Complexes with cell membranes receptors of modified ferritins for cancer theranostics .