Projects

Europe still sees a quarter of the world's cancer cases each year, making cancer the second leading cause of death and illness in the region after cardiovascular diseases. Unless we take decisive action, lives lost to cancer in the EU are set to increase by more than 24% by 2035, making it the leading cause of death in the EU. Cross-border collaboration can address this challenge by combining data from various modalities and sources, extracting meaningful insights to deepen our understanding of cancer. However, ethical, legal, and national regulations, along with data access processes, including differing interpretations of the EU GDPR create significant hurdles. Technical interoperability issues across European cancer RIs, and patients' and citizens' rights to control who uses their personal information and for what purposes further complicate data sharing. The project will provide European researchers, SMEs, and innovators with a decentralized collaborative network, “UNCAN-CONNECT,” for cancer research. It consists of both technical components, a governance, compliance, and operational framework based on the UNCAN blueprint, with the goal of operationalizing it. The objective is to facilitate access to cancer data, promote open science, and revolutionize cancer research and treatment by co-creating an open-source federation of federations platform. It will be developed using specific use cases focused on six major cancer types: Paediatric, Lymphoid malignancies, Pancreatic cancer, Ovarian, Lung, and Prostate cancers and active collaboration with a diverse range of stakeholders,including researchers, SMEs, industrial end users, and citizens. It will build on existing European RIs such as BBMRI as well as initiatives like EOSC4CANCER, CanSERV, EUCAIM, to enable seamless storage, access, sharing, and processing of data across Member States and associated countries. This approach will foster interoperability and collaboration, accelerating progress in cancer research. This action is part of the Cancer Mission clusters of projects 'Understanding' established in 2022.

To sustain life and its quality on Earth, the EU has established several initiatives for the implementation of the Green Deal: Zero Pollution Action Plan, Farm to Fork and Green Deal Industrial Plan, among many others. All of these require significant innovation, based on new knowledge and skills – research, training and education – coupled with industry adaptation, civil society engagement and smart regulation, which is a challenge globally. More importantly, we need significantly more people who can carry out this innovation. The main objective of “Innovative Chemistry and Biotechnology for a Sustainable Future” (INNOCHEMBIO) is to train future experts of sustainable chemistry and biotechnology, helping Europe to take the next steps in the green transition. The solutions and trained experts can reduce the environmental impact of the chemical and agricultural industries, offer eco-friendly analytical techniques, and assess the safety of new materials. This will be achieved through interdisciplinary research projects in an international research environment, collaboration with the industry, the public sector and the civil society, via a comprehensive quadruple-helix based training programme. As a result, our graduates will not only become experts in their respective fields, but leaders and spokespersons. Eventually, through dedicated career planning, we provide skilled workforce to all 4 sectors of the helix. INNOCHEMBIO is an international consortium led by TalTech, with over 100 years of experience in chemistry and biotechnology research and training. INNOCHEMBIO will achieve its objectives by recruiting 15 PhD candidates in up to two calls offering fellowships for 48 months. During this period, the candidates will receive discipline specific training both in Estonia and abroad by working on their research project; broader training through courses offered at TalTech and by our partners; and experience working in the private sector.

The research infrastructure on experimental studies and applications of cellular processes aims at gathering national know-how in the field of cell and molecular biology, and aims at setting up an instrumental capability to develop competence and services in the fields of microbial and mammalian cell processes and their applications. The infrastructure will be built up jointly by the University of Tartu, Tallinn University of Technology, Tallinn University, Estonian University of Life Sciences and the Institute of Chemical Physics and Biophysics. The vision is to become a know-how and service centre to partner health, biotechnology and environment-focused public sector organisations, medical institutions, biotechnology and pharmacological companies. The focus will be on acquiring and setting up relevant instrumental complexes, development and offering of services, popularisation and dissemination of the field in order to ensure sustainability of researchers and future activities.

Neural plasticity is the ability of nervous system to change its activity in response to stimuli by reorganizing its structure, functions, or connections and this is the main cellular basis for memory. Activity-regulated genes play crucial roles in the formation of neuronal plasticity, and dysregulation of this process gives rise to various nervous system disorders. The neurotrophin BDNF is among the best-studied activity-regulated genes, and its polymorphisms are associated with impairments in human cognition. Our results also place the basic helix-loop-helix transcription factor TCF4, that is implicated in a variety of psychiatric and autism spectrum disorders, to the group of activity-regulated transcription factors. The aim of this project is to study gene regulation in intellectual disability and autism spectrum disorders with emphasis on disease-associated transcription factors TCF4, SATB2, FOXP1, and neurotrophin BDNF for finding new drug targets.

The nervous system consists of multiple cell types with distinct physiological specializations and gene expression patterns. In tissue, these cells form a complex, intertwined network that is subject to constant interaction between different cell types. This complexity poses a challenge for researchers in both separating cell types for analysis as well as studying interactions and information transfer between cells. In this application, we propose a molecular neuroscience study addressing both aspects. First, we are developing proteomics methods to allow analysis of newly synthesized proteins on a cell type-specific basis. Second, we shall use novel genetic tools for cell type-specific stimulation and gene expression analysis in primary co-cultures of neurons and astroglial cells. We shall use this system to probe gene expression signatures in neuron-astrocyte communication and determine the transmitters that form the basis of this communication.

Projekt OptimaMind keskendub ajapiiranguga söömisele, et parandada aju tervist ja võidelda vananemisega kaasnevate väljakutsetega. Ajalooliselt oli inimeste juurdepääs toidule sageli juhuslik, muutes vahelduva paastumise (teise nimega aeg-restrikteeritud söömise (TRE)) elu loomulikuks osaks. See ajalooline kontekst loob aluse TRE võimalike eeliste mõistmiseks tänapäeval, eriti kognitiivse tervise kontekstis. On näidatud, et TRE kutsub esile adaptiivseid molekulaarseid muutusi, mis kaitsevad rakuressursse, parandades samal ajal füüsilist ja kognitiivset jõudlust. Sellised muutused hõlmavad süsteemse põletiku vähenemist ja raku antioksüdantide potentsiaali suurenemist. Üks TRE mõju näidetest on beeta-hüdroksübutüraadi (BHB), ketoonkeha, mis parandab kognitiivseid funktsioone, tootmine. Maksas toodetud BHB on oluline energiasubstraat, millel on võrreldes teiste energiaallikatega kasulikumaid omadusi. Ja vastupidi, sagedane toidutarbimine ja vähene füüsiline aktiivsus võivad pärssida BHB tootmist, vähendades seega selle positiivset mõju. Projekti OptimaMind eesmärk on uurida erinevate meetodite abil TRE mõju kognitiivsete funktsioonide biomarkeritele, eriti vananevas elanikkonnas. Kavandatavas projektis kasutatakse Euroopas olemasolevaid biopankade proove ja erinevaid paastuprotokolli kohordi andmeid, et uurida neuroprotektiivseid biomarkereid erinevates populatsioonides. Oodatavad tulemused hõlmavad uusi teadmisi TRE-st kui mittefarmakoloogilisest strateegiast kognitiivse pikaealisuse suurendamiseks ja dementsuse ennetamiseks. Projekti eesmärk on ka teavitada tervishoiuteenuse osutajaid ja avalikkust praktilistest tõenduspõhistest strateegiatest aju tervise säilitamiseks. OptimaMind mõjutab rahvatervise soovitusi, kliinilisi tavasid ja heaolutööstust, mille eesmärk on lõpuks parandada kognitiivset tervist ja elukvaliteeti vananevas elanikkonnas.

Astrocytes comprise one of the main cell types in the central nervous system (CNS), and it is now recognized that they have important roles in ensuring proper development and homeostasis of the CNS, with astrocyte dysfunction contributing to all major neurological disorders. Recent studies have shown that these cells undergo dramatic transcriptional changes in response to neuron-derived stimuli. However, what are the astrocyte-specific mechanisms that regulate these changes are still largely unknown. Here, this issue will be tackled using state-of-the art functional genomic approaches to generate a comprehensive map of the astrocyte-specific regulatory elements (with a focus on enhancers) and transcription factors that govern stimuli-induced gene expression changes. This will provide unique and original insights into the mechanisms that control stimuli-induced gene expression in non-neuronal CNS cells, with potential implications for the understanding of several neuropathologies.

"Pitt-Hopkins syndrome is a cognitive functional disorder, caused by a de novo genetic mutation of one allele of the transcription factor 4 (TCF4) gene. It has been reported that postnatal restoration of TCF functions in Pitt-Hopkins syndrome animal model (partially) rescues the phenotype, indicating that therapeutic approaches increasing TCF4 levels or activity might also help patients. It has also been reported that inhibiting histone deacetylase activity increases TCF4 transcriptional activity and rescues memory deficiencies associated with TCF4 haploinsufficiency in a mouse model. These effects are likely conveyed by some TCF4 co-repressor, such as ETO/RUNX1T1 recruiting HDACs. However, HDAC inhibitors have a very broad effect on the cellular transcription and can cause various side-effects. Here, we hypothesize that by modulating the activity of specific TCF4 co-activators or co-repressors or their interaction with TCF4 could increase TCF4-dependent transcription, thus alleviating the symptoms of Pitt-Hopkins syndrome and have less side effects for the patients. To this end, we pursue to thoroughly identify the co-regulators participating in TCF4-dependent transcription, and to find means to modulate their activity. The specific aims are as follows: (1) Identify the co-regulatory proteins of different TCF4 protein isoforms. (2) Determine the mechanism of action and the interacting regions between TCF4 and co-regulatory proteins. (3) Develop means to modulate the transcriptional activity or binding of the TCF4 co-regulatory proteins."