Periodic Reporting for period 3 - cGEM (the Center for Genomics, Evolution and Medicine)
Periodo di rendicontazione: 2021-09-01 al 2023-12-31
The overall objective of the project is to establish an outstanding research team to form an integrated Center for Genomics, Evolution and Medicine (cGEM). The center will bring together the scientific expertise from three institutions: the Estonian Biocentre (EBC) and the Estonian Genome Center (EGC) which will be consolidated to form the Institute of Genomics at University of Tartu (IGUT) in January 2018, and the Institute of Clinical Medicine (ICM). The scientific expertise and the synergy between the three scientific hubs complemented with ERA Chair holder and the team, will create the research capacity for tackling the aims set for the project. This capacity will be built to apply a holistic approach to understand the evolutionary driving forces that have led to common diseases; develop disease risk prediction models applicable in different populations, and explore the means for translating these findings into suitable input for everyday clinical practice. cGEM aims to apply advancements in genomic medicine in an evolutionarily-aware framework to account for different evolutionary pathways of populations which have led to differences in susceptibility to common diseases. This requires the knowledge about the genetic risk factors for diverse ethnic groups and the tools to highlight the underlying genetic predisposition to diseases in complex human populations. Different evolutionary histories have led to differences in susceptibility to diseases, and moreover, using genetic data for estimating disease risk is heavily dependent on availability of reference data from relevant populations. Therefore, findings from one population cannot be directly extrapolated to other populations, restricting the application of genomic medicine in routine healthcare. To overcome this limitation, the cGEM will utilize our international collaborations and in-house biobanks to advance the personalized medicine solutions for admixed populations for predicting risk of certain complex diseases, including metabolic and cardiovascular diseases, and cancers.
The cGEM project has been successful in generating a multidisciplinary research group that combines together evolutionary genomics, population genetics together with personalized medicine and clinical research. From studying natural selection, migration effects and how past admixture events with ancient and archaic human populations have profoundly influenced immune-related phenotypes in contemporary populations up to establishing experimental pipelines for differentiating induced pluripotent stem cells (iPSCs) from blood and urine. cGEM has helped to intertwine the research directions of the three institutes that were brought together with this grant with numerous joint research projects and grant proposals. The new research directions introduced during the cGEM project, induced pluripotent stem cells (iPSCs) and immunoprofiling, investigation archaic humans are new directions that are still to have an effect to the overall performance of the institute. These highly promising directions will be the stepping stone for further development
The synergy created with the cGEM grant together with the development of the Estonian Biobank and the entrepreneurial ecosystem around it will be the driving force for the future success of research excellence at the Institute of Genomics (UT)
The cGEM project has been successful in generating a multidisciplinary research group that combines together evolutionary genomics, population genetics together with personalized medicine and clinical research. From studying natural selection, migration effects and how past admixture events with ancient and archaic human populations have profoundly influenced immune-related phenotypes in contemporary populations up to establishing experimental pipelines for differentiating induced pluripotent stem cells (iPSCs) from blood and urine. cGEM has helped to intertwine the research directions of the three institutes that were brought together with this grant with numerous joint research projects and grant proposals. The new research directions introduced during the cGEM project, induced pluripotent stem cells (iPSCs) and immunoprofiling, investigation archaic humans are new directions that are still to have an effect to the overall performance of the institute. These highly promising directions will be the stepping stone for further development
The synergy created with the cGEM grant together with the development of the Estonian Biobank and the entrepreneurial ecosystem around it will be the driving force for the future success of research excellence at the Institute of Genomics (UT)
Period I:
By the end of period I the ERA-Chair holder (Anders Eriksson) has been recruited and has started building his research team. We have successfully filled 2 out of 3 senior researcher positions and are in the middle of negotiations for filling the 3rd position. The calls for PhD students and postdocs are being launched. The team is currently compiling the research plan of the project.
Period II:
By the end of period II we have successfully filled all three senior researcher positions, positions for postdocs and PhD students are also filled.
- Evolutionary and Population Genomics group is led by associate professor Michael Dannemann. Group has established new international collaborations with labs of dr Fernando Racimo from University of Copenhagen and dr Vivian Slom from University of Tel Aviv. Also, group is closely working with members of the host institute and collaboration with cGEM's Bioinformatic and Medical Genomics group has intensified. Group has joined a formal collaboration between UTARTU and the FinnGen consortium. The current team designed additional projects that aim at understanding how adaptation and Neandertal admixture influenced disease-associated variation in people today.
- Bioinformatics and Medical Genomics group is led by associate professors Tõnis Org, Irene Gallego Romero and Georgi Hudjašov. Activities by the group: 1.In-depth ancestry analysis of Estonian Biobank (EBB) data using computational approach; 2. History of natural selection in EBB samples; 3. Functional validation of genomic variants at scale via massively parallel reporter assays (MPRA); 4. Generation of iPSC lines for future functional studies
- Molecular Medicine group is led by associate professor Kaia Palm. In fall 2020 the team was formed (Kaia was the last senior researcher, who was recruited) and ethical permits were obtained and experimental studies started. Team's studies were aimed at confirming the suitability of mimotope-variation analysis (MVA) as the technology enabling a highly precise, personalized and global view on the state of the immune system associated with different clinical conditions. For that, data of > 500 individual MVA immunoprofiles were generated and analyzed regarding developing solutions for less-invasive testing on three clinical models (gonadotropins and autoimmunity, mother-neonate-infant physiological and pathologic immunity, antibody-associations with HLA haplotypes).
Period III:
The team formulated under cGEM project was able to fully commit to the research directions set out. In the course of the project, our research directions underwent continuous adjustments to explore innovative and new avenues aimed at addressing our research questions and integrating the latest methodological advancements. This strategic approach was implemented to ensure the effective delivery of project results and to enhance the research endeavours of the institute. In sum, despite challenges related to some unforeseen experimental difficulties and pandemic-related delays, the research strategy was largely successful achieving the objectives set out. The research results were formulated into 29 research publications. These results were in turn disseminated through participation on international high level scientific events in the respective field and by organising 4 conferences, 2 winter-schools and 2 entrepreneurial events.
By the end of period I the ERA-Chair holder (Anders Eriksson) has been recruited and has started building his research team. We have successfully filled 2 out of 3 senior researcher positions and are in the middle of negotiations for filling the 3rd position. The calls for PhD students and postdocs are being launched. The team is currently compiling the research plan of the project.
Period II:
By the end of period II we have successfully filled all three senior researcher positions, positions for postdocs and PhD students are also filled.
- Evolutionary and Population Genomics group is led by associate professor Michael Dannemann. Group has established new international collaborations with labs of dr Fernando Racimo from University of Copenhagen and dr Vivian Slom from University of Tel Aviv. Also, group is closely working with members of the host institute and collaboration with cGEM's Bioinformatic and Medical Genomics group has intensified. Group has joined a formal collaboration between UTARTU and the FinnGen consortium. The current team designed additional projects that aim at understanding how adaptation and Neandertal admixture influenced disease-associated variation in people today.
- Bioinformatics and Medical Genomics group is led by associate professors Tõnis Org, Irene Gallego Romero and Georgi Hudjašov. Activities by the group: 1.In-depth ancestry analysis of Estonian Biobank (EBB) data using computational approach; 2. History of natural selection in EBB samples; 3. Functional validation of genomic variants at scale via massively parallel reporter assays (MPRA); 4. Generation of iPSC lines for future functional studies
- Molecular Medicine group is led by associate professor Kaia Palm. In fall 2020 the team was formed (Kaia was the last senior researcher, who was recruited) and ethical permits were obtained and experimental studies started. Team's studies were aimed at confirming the suitability of mimotope-variation analysis (MVA) as the technology enabling a highly precise, personalized and global view on the state of the immune system associated with different clinical conditions. For that, data of > 500 individual MVA immunoprofiles were generated and analyzed regarding developing solutions for less-invasive testing on three clinical models (gonadotropins and autoimmunity, mother-neonate-infant physiological and pathologic immunity, antibody-associations with HLA haplotypes).
Period III:
The team formulated under cGEM project was able to fully commit to the research directions set out. In the course of the project, our research directions underwent continuous adjustments to explore innovative and new avenues aimed at addressing our research questions and integrating the latest methodological advancements. This strategic approach was implemented to ensure the effective delivery of project results and to enhance the research endeavours of the institute. In sum, despite challenges related to some unforeseen experimental difficulties and pandemic-related delays, the research strategy was largely successful achieving the objectives set out. The research results were formulated into 29 research publications. These results were in turn disseminated through participation on international high level scientific events in the respective field and by organising 4 conferences, 2 winter-schools and 2 entrepreneurial events.
The most important long-term impacts of the cGEM project are the following:
- increased research excellence at the cGEM
- increased attractiveness of the cGEM for internationally excellent and mobile researchers
- more active and successful participation in international competitive research funding programmes
- more active partnerships with private sector stakeholders
- innovative Ph.D. education programmes
- regular internal and external research assessments for scientific and socio-economic relevance
- increased attractiveness of (academic) research career, in particular, elimination of the obstacles hindering practicing dual MD/Ph.D. path
- increased research excellence at the cGEM
- increased attractiveness of the cGEM for internationally excellent and mobile researchers
- more active and successful participation in international competitive research funding programmes
- more active partnerships with private sector stakeholders
- innovative Ph.D. education programmes
- regular internal and external research assessments for scientific and socio-economic relevance
- increased attractiveness of (academic) research career, in particular, elimination of the obstacles hindering practicing dual MD/Ph.D. path