ERC funding for new drug development

Constantinos Demetriades receives Proof of Concept Grant from the European Research Council

The European Research Council (ERC) is funding Constantinos Demetriades, research group leader at the Max Planck Institute for Biology of Ageing to develop new specific inhibitors of a protein complex called mTORC1. This complex plays a central role in cell growth and metabolism and dysregulation of its activity is tightly linked to ageing and human diseases such as cancer or neurological disorders.

Natural and synthetic inhibitors targeting mTOR (as part of the mTORC1 and mTORC2 protein complexes) have been tested in various clinical settings, however with little success and limited applicability so far, mainly due to low efficacy or adverse effects. A major limitation of already existing compounds is their inability to specifically inhibit all mTORC1 functions, without affecting the activity of mTORC2. “This is not a simple task, as both complexes contain the same active molecule, the enzyme mTOR, therefore specificity is hard to achieve”, points out Demetriades.

The Demetriades group, together with a team of scientists from DKFZ Heidelberg and the University of Fribourg, Switzerland, recently identified malonyl-CoA, a metabolic intermediate of fatty acid (FA) biosynthesis, as the first described endogenous metabolite that acts as an ATP-competitive inhibitor of mTORC1. Interestingly, increasing malonyl-CoA levels in cells caused the specific downregulation of mTORC1 activity, but did not influence mTORC2. "This highlights malonyl-CoA as a very attractive and promising mTORC1 inhibitor with improved properties over existing compounds," says Demetriades. With the support of this ERC grant, the team’s goal is now to develop malonyl-CoA derivatives as a new class of more potent and specific mTORC1 inhibitors. “This project also highlights the importance of fundamental research, and is a beautiful example of how curiosity-driven science can drive innovation and may lead to applications that could—one day—benefit society,” he notes.

The ERC Proof of Concept (PoC) grant is aimed at researchers who have already received ERC funding for their research project and want to explore the commercial or societal potential of their research. According to the ERC, the aim is to advance ERC-funded ideas from frontier research to innovation. "Receiving a PoC grant from the ERC is a great honor and comes as important recognition of the high-quality research performed by the scientists in my group,” adds Demetriades.

About Constantinos Demetriades

Constantinos Demetriades holds a degree in Biology from the Aristotle University of Thessaloniki and completed his PhD at the Biomedical Sciences Research Center 'Alexander Fleming' in Athens and the Aristotle University of Thessaloniki, Greece. He then joined the group of Aurelio Teleman at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, as a postdoctoral researcher. Since January 2017, Demetriades has been a Max Planck Research Group Leader at the Max Planck Institute for the Biology of Ageing in Cologne, Germany. In November of the same year, he received a Starting Grant from the ERC.

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