Research funded by ERC
The European Research Council (ERC) provides highly competitive funding which currently supports 2 research teams led by top researchers at the University of Tartu. One of them is ERC Starting Grant. The latest is a Consolidator Grant.
European Research Council (ERC) grants support individual researchers who wish to pursue their frontier research. The ERC encourages in particular proposals that cross disciplinary boundaries, pioneering ideas that address new and emerging fields and applications that introduce unconventional, innovative approaches.
ERC Starting Grants aim to support up-and-coming research leaders who are about to establish a proper research team and to start conducting independent research in Europe.
ERC Consolidator Grants are designed to back up researchers who want to establish their research teams and continue developing a successful career in Europe. The scheme also strengthens independent and excellent new individual research teams that have been recently created.
Commercialising a novel glioblastoma targeted therapy and a companion diagnostic compound
Glioblastoma (GBM), is the most aggressive form of primary brain cancer and is diagnosed in 22,000 people per year in the EU. GBM is the most aggressive primary brain cancer and, by annual incidence, the most common type of malignant brain tumour. Despite aggressive treatment, the cancer always recurs. The average survival after diagnosis is 12 to 15 months, with less than 3% to 5% of patients surviving longer than 5 years. The current standard of care extends overall survival to ~14 -16 months. Current valuation of the global GBM treatment market is estimated to be €615 million per year, and it is predicted to increase to over €3.08 billion by 2024 (compound annual growth rate of 17%), based on the projected approval of new therapies including Opdivo and Optune. The main aim of this ERC PoC proposal is to probe the commercial viability of two types of tumour-targeted payload hybrids, one as an improved chemotherapeutic treatment, and the other as a precision-guided imaging agent for PET/MRI-based diagnosis. Our goal is for the former to become the clinician’s chemotherapy of choice in the adjuvant phase of GBM treatment; and for the latter to be incorporated into PET and MRimaging procedures as a method for identifying and diagnosing GBM, as well as a companion test for stratification of patients for therapy.
ERC Proof of Concept Grant 2017-2019
PHOSPHOPROCESSORS - Biological signal processing via multisite phosphorylation networks
Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation.
We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1- dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.
ERC Consolidator Grant 2015-2020
CliomaDDS - Brain tumor penetrating peptides
Our project addresses a major problem in therapy of solid tumors: poor penetration of anti-cancer drugs into tumor tissue and to infiltrating tumor cells.
Recently, we have identified tumor penetrating peptides (TPP) that trigger specific penetration of co-administered un-conjugated drugs deep into tumor and increase their therapeutic index. Current TPP target angiogenic tumor vessels and may not be suitable for targeting slow-growing tumors and invasive tumor cells. TPP are composed of functional modules (tumor recruitment motif, cryptic tissue penetrating C-end Rule element, and a protease cleavage site), which can be rearranged to yield peptides of novel specificities. Our goal is to develop TPP platform for delivery of co-administered drugs to the deadliest brain tumor – glioblastoma (GBM). High-grade glioma is a target that is particularly evasive and well-suited for tissue penetrative drug delivery. We will develop glioma-specific TPP (gTPP) by combination of in vivo and ex vivo phage display of constrained peptide libraries on state-of-the-art glioma animal models. These gTPP will be able to penetrate gliomas (and potentially other tumors) independent of their angiogenic status, and to deliver drugs to infiltrating malignant cells far from the bulk glioma lesion. We will characterize, validate, and optimize the gTPP platform for enhanced glioma delivery of co-injected drugs. These studies will provide the preclinical data needed to advance the gTPP combination therapy of glioma to GLP toxicology and subsequent IND filing.
ERC Starting Grant 2012-2016
Professor Lauri Mälksoo dr. iur
The central research question of our project is: what impact does the increasingly non-liberal orientation of the government of the Russian Federation have on the Russian doctrine and practice of international law?
As the West and Russia hope to further build their relationship on international law, is it still the same international law that they are talking about? We aim to provide systematic empirical evidence on the use and conceptualization of international law in the Russian Federation. But we intend to go further than that. The project has also a wider theoretical ambition since we intend to analyze the situation in Russia as an example of something beyond Russia itself, namely from the viewpoint of the question of how non-liberal States understand and practice international law. Whether non-liberal States 'behave worse' in respect to international law than liberal States is one of the most important debates in the post-Cold War international legal theory. To combine these two questions - Russia and how non-liberal States relate to international law - promises ground-breaking new insights. Our method includes, beside obvious classical tools of international legal research, using IR theories of constructivism and liberalism. Moreover, we will conduct interviews with Russian judges, politicians and legal academicians in order to get a more nuanced and realistic view on the conceptualization and use of international law in Russia.
ERC Starting Grant 2009-2014