SEARMET project consists of four partner institutions:
Estonian University of Life Sciences (Estonia) will be the primary recipient of training and consultation, so that it can build its capacity and scientific excellence in the areas of Animal Reproduction and Embryo technologies. EMU has a strong foundation, being one of the top institutions in these fields in Eastern Europe. For example, EMU has bovine in vitro production experience since 1992. EMU introduced bovine somatic cell nucleus transfer cloning techniques in 2007 and produced bovine cloned embryos since spring 2008 on a regular basis for the research purposes. In 2012, the first cloned calf was born, EMU was the first university in Estonia where whole genome sequencing of Estonian Holstein cow and bull genome were carried through. EMU is the only university in Estonia for the integration of academic education and research activities in the field of sustainable use of natural resources, food production, technology and veterinary medicine. The Institute of Veterinary Medicine and Animal Sciences performs teaching and R&D activities in the field of animal nutrition, genetics and breeding, reproductive biology, biotechnology, animal health, food safety and food technology. Research and development at the Department of Reproductive Biology are focused on fertility and infertility in large animals and reproductive biotechnology. EMU still has significant gaps in technical expertise and institutional networking and infrastructure that has limited its impact and hinders future advancement. You can find more information from https://www.emu.ee/en/
Description and main tasks
The history of the Estonian University of Life Sciences (EMU) goes back to 1848 when the Tartu Veterinary Institute was founded. In 1919, the Faculty of Agriculture was founded at the Tartu University. Tartu Veterinary Institute became the Faculty of Veterinary Science of the Tartu University. In 1951, an independent university - the Estonian Academy of Agriculture - was founded on the basis of Tartu University faculties of Agriculture, Forestry and Veterinary Science. From 1991, the institution was called the Estonian Agricultural University and from 2005, the Estonian University of Life Sciences. EMU is the only university in Estonia the priorities of which in academic and research activities provide the sustainable development of natural resources necessary for the existence of mankind as well as the preservation of heritage and habitat. EMU is the only university in Estonia for the integration of academic education and research activities in the field of sustainable use of natural resources, food production, technology, veterinary medicine, rural life and economy. According to QS World University Rankings by subject, the Estonian University of Life Sciences is one of top 200 universities in the world in the field of agriculture and forestry. The Thomson Reuters Essential Science Indicators database places the Estonian University of Life Sciences into the top 1% most cited research facilities in the world in the field of plant and animal science.
The Institute of Veterinary Medicine and Animal Sciences of performs teaching and R&D activities in the field of animal nutrition, genetics and breeding, reproductive biology, biotechnology, animal health, food safety and food technology. Research and development at the Department of Reproductive Biology are focused on fertility and infertility in large animals and reproductive biotechnology. Special attention is paid to the problems of ovarian function, luteal function and embryonic mortality in dairy cows in high input environments (prof A. Waldmann), oocyte and embryo quality and biotechnology of reproduction (prof Ü. Jaakma), diagnostics and treatment of reproductive disorders (J. Kurykin, PhD), sperm quality and male (in)fertility (T. Hallap, PhD). During last years, there is a particular interest to genomics and transcriptomics of early development in mammals (prof S. Kõks).
EMU has evaluated importance of different sperm characteristics from the aspect of their fertilizing ability, including usefulness of various conventional (morphology, subjectively estimated motility, and hypo-osmotic resistance) and more advanced sperm quality tests (computer-assisted sperm motion analysis, flow cytometry analysis of mitochondrial activity, membrane integrity, and membrane fluidity) in assessing frozen-thawed semen. They have also studied the influence of sperm preparation methods prior to quality measurements as well as effects of age and breed on semen quality, and are working on development of models for the bull fertility prediction based on laboratory measurements.
EMU has bovine in vitro production (IVP) experience since 1992. They have introduced bovine somatic cell nucleus transfer cloning techniques and produced bovine cloned embryos since 2009 on a regular basis for the research purposes. In 2012, the first cloned calf was born. Technology for the large animal cloning has formed a basis for the further research on transgenic technologies in cooperation with the Competence Centre on Health Technologies (CCHT). EMU is a member of several research networks, including COST networks in epigenetics and large animal models. They work in good collaboration with the Transgenic Technology Core Laboratory and Institute of Physiology of University of Tartu, Faculty of Veterinary Medicine of the Swedish University of Agricultural Sciences, Gene Center of the University of Munich, INRA (France) and many others.
Core lab competences of EMU include generation of fetal cell lines, somatic cell nucleus transfer and in vitro culture of bovine embryos up to the blastocyst stage. The competence of the production of gene construct coupling the gene for the particular drug with a DNA signal directing production of it into the mammary gland is essential for the generation of transgenic fibroblast cell lines that are used for the SCNT cloning. Competence of generation of corresponding transgenic mouse models provided by UT, has had crucial importance in the development of transgenic technology in large animals, as a fast method for the preliminary evaluation of the efficiency of the gene construct integration into the genome and activation during the lactation. Excellent veterinary competence provided by the EMU Large Animal Clinic is an inevitable part of generation of transgenic animals. This includes experience in embryo transfer, monitoring of ongoing pregnancies, early detection of fetal and placental abnormalities, planning the Caesarean section if necessary and intensive care of newborns. Competence of purification and characterization of peptides from the milk that is necessary for the initial evaluation of milk as raw material for the pharmaceutical industry, is provided by researchers of CCHT and TBD Biodiscovery.
The University of Sheffield (Great Britain) is established as one of the best-regarded universities in the world, consistently positioned in the top 75 in the World University Rankings, with an annual turnover of £400m. In regards to this project, SU has an excellent position in reproductive and developmental medicine research and networking within Europe and the world. Both recent European wide Cost Actions in this field i.e., GEMINI (FA0702, http://www.cost-gemini.eu/) and Epiconcept (FA1201, http://epiconcept.group.shef.ac.uk/) have been initiated and managed by SU. Recent developments in understanding of innate immune responses during the periconception period as well as deciphering the epigenetics, genomics and proteomic interactions taking place during the periconception period has been either discovered by researchers based in SU or has been reported in collaboration with SU researchers. You can find additional information http://fazelilab.group.shef.ac.uk/
Description and main tasks
Fazeli’s Research group within Academic Unit of Reproductive and Developmental Medicine has a history of over a decade productive research on maternal communication with gametes and embryo. Fazeli’s group has defined the importance of innate immune system in successful establishment of this communication. The group has a wide range of experience at the advance levels of application of genomics, epigenomics and proteomics technologies to understand maternal communication with gametes and embryo. Their model systems has ranged from Human to pig, cattle, sheep, fly (Dorosophila) and different families of fish ranging from Guppies to Sea horses. The group for the first time has coined the concept of early communication between gametes and the maternal tract. They have extended this concept to computational modelling exercises allowing prediction of maternal communications with gametes and embryo outcomes. Recently with the advances of epigenetic understanding of periconception environment, Fazeli’s group is leading an EU COST Action program (FA1201) “Epiconcept”, involving around 30 different EU member states to understand how periconception environment can affect epigenomic profile of the offspring affecting its health and development in the adulthood.
University of Copenhagen (Denmark) operates the Stem Cell and Embryology Group that will work with EMU directly in the SERMET project. The group has strong experience in the production of bovine embryos. With respect to the stem cell activities, the Group holds competences in human and porcine iPSC reprogramming and neural differentiation of iPSC including all necessary characterization of stem cells and differentiated cells. Likewise, the Group has competences in CRISPR-based genome editing for production of isogenic control cell lines and induction of specific mutations in normal lines. For the activities, the group holds competences for oocyte maturation, fertilization and initial embryonic development in vitro, for development of relevant media for these procedures and for molecular and cell biological characterization of early embryos. The group closely collaborates with commercial bovine in vitro production facilities as well as universities around the world, in particular Giessen University, Colorado University and the University of Florida. UCPH has extensive experience making connections to industry, including having strategic partnerships with both large and small firms in the pharmaceutical sector. This includes Novo Nordisk, which markets its hormone therapy and other products in more than 180 countries; GlaxoSmithKline, which develops and makes medicines and vaccines in over 170 countries and has established research collaborations with more than 3,000 organisations. One member of the UCPH team is Founder and CSO of EmbryoTrans Biotech, a company that develops serum-free ready-to-use in vitro fertilization (IVF) media for animal reproduction for the UK company IVF Bioscience. They also have a strong relationship with Lundbeck, which markets pharmaceutical products in 100 countries. Within the university there is an extensive collaboration with other departments, allowing us to do extensive analysis such as gene expression analysis, gene modification, differential staining as well as electron microscopy. You can find more information http://ikvh.ku.dk/english/
Description and main tasks
The Stem Cell and Embryology Group at University of Copenhagen (UCPH) has a strong focus on (1) human and porcine induced pluripotent stem cells (iPSC) for modeling neurodegenerative disorders and (2) in vitro production (IVP) of bovine embryos. With respect to the stem cell activities, the Group holds competences in human and porcine iPSC reprogramming and neural differentiation of iPSC including all necessary characterization of stem cells and differentiated cells. Likewise, the Group has competences in CRISPR-based genome editing for production of isogenic control cell lines and induction of specific mutations in normal lines. For the IVP activities, the Group holds competences for oocyte maturation, fertilization and initial embryonic development in vitro, for development of relevant media for these procedures and for molecular and cell biological characterization of early embryos.
The University of Tartu (Estonia) is Estonia's leading centre of research and training. The partner institute inside the University of Tartu for the present project is Department of Pathophysiology. Located in UT’s Faculty of Medicine, The Department of Pathophysiology is focused on the research-based teaching of the basis of disease at all levels of medical education. The Department of Pathophysiology has expertise in cellular energy metabolism, disease models, genomics (genome and exome sequencing, RNAseq, genotyping), human studies, biobanking and complex data analysis. UT will participate in some training activities offered by SU and UCPH and will work with EMU to develop a strategy for translating animal research results into forms that can be used to benefit human health, such as a better understanding of human reproductive health. EMU and UT will in turn work together to try and exploit potential research results by reaching out to the biopharmaceutical industry. You can find additional information http://www.ut.ee/en
Description and main tasks
University of Tartu is Estonia's leading centre of research and training. Founded in 1632, the University of Tartu has been dedicated to the broad-based development of its various research areas, and remains today the only classical university in Estonia. University of Tartu is an internationally renowned research university, and the centre of academic life, culture and high-technology innovation in Estonia. University of Tartu belongs to the top 3% of world's best universities (Times Higher Education World University Rankings, 2011–2014). The robust research potential of the university is evidenced by the fact that it is the only Baltic university that has been invited to join the Coimbra Group, a prestigious club of renowned research universities. University of Tartu includes nine faculties and four colleges. To support and develop the professional competence of its students and academic staff, the university has entered into bilateral co-operation agreements with 64 partner institutions in 23 countries.
The partner institute inside the University of Tartu for the present project is Department of Pathophysiology. Located in UT’s Faculty of Medicine, The Department of Pathophysiology is focused on the research-based teaching of the basis of disease at all levels of medical education. The main research areas are the pathogenesis of musculoskeletal diseases, chronic inflammatory diseases and degenerative diseases. The focus is on bioenergetics and pathophysiological studies of heart failure and age-related sarcopenia. Further interaction mechanisms of glycolysis and oxidative phosphorylation and functional complexes of mitochondria with ATPases are studied. The research aims to describe changes in these processes across different pathophysiological conditions (atrial dilatation, inflammation, ER stress). The specific impact of altered cellular bioenergetics in the pathogenesis of sarcopenia and the relationship between energy metabolism expression of differentiation markers and activation of signaling systems are under investigation.
Previous research has studied the alterations in the regulation of oxidative phosphorylation by extramitochondrial calcium in brain cells and changes in the crosstalk between oxidative phosphorylation and glycolysis in the pathogenesis of cardiac and skeletal muscle disorders (cardiac failure and sarcopenia). In addition, the role of some signaling pathways (HIF-1alpha, PKB/Akt) and metabolic substrates (creatine) in cellular damage during heart failure and sarcopenia has been studied. It has been found that aged skeletal muscles have reduced regenerative potential combined with disturbed energy metabolism, which increases vulnerability of myoblasts to hypoxia and calcium overload. In their research program the institute combines systems genetics with more focused studies on cellular bioenergetics and ER stress.
Department of Pathophysiology has expertise in cellular energy metabolism, disease models, genomics (genome and exome sequencing, RNAseq, genotyping), human studies, biobanking and complex data analysis.