Research

The mission of our Institute is to advance new fundamental understanding of the molecular, cellular and etiological basis of human diseases. We integrate molecular medicine research, Technology Centre and Biobank Infrastructure “under one roof” and thereby promote translational research and adoption of personalised medicine in health care. As part of the Nordic EMBL Partnership for Molecular Medicine, we follow the principles of EMBL partnerships. This means aiming to scientific excellence and establishing mechanisms for independent scientific review of the research activities; scientific integrity and good scientific practice; high level, regular international evaluations with consequences for tenure and funding, as well as commitment to significant levels of staff turnover.

The research at FIMM focuses on two main areas:

In 2014, there were altogether sixteen research groups at FIMM, including six FIMM-EMBL groups, three FiDiPro Professors and one FiDiPro Fellow. The disease areas of interest for the research groups cover cancer, cardiovascular disease, diabetes, immunological diseases, neurology, neuropsychiatric diseases and viral infections.

From the beginning of 2014, Dr. Peter Horvath, the first FiDiPro Fellow of FIMM and the University of Helsinki, further strengthened FIMM’s FiDiPro network with three FiDiPro Professor projects already running. FiDiPro - the Finland Distinguished Professor Programme - led and financed by the Academy of Finland and Tekes enables distinguished researchers to work and team up with Finnish academic researchers. Dr. Horvath was recruited to the project by Tekes funding. The aim of his project "Next generation image analysis solutions - towards image-based diagnostics" is to find computational solutions to challenges in biomedical imaging. Dr. Horvath comes from ETH Zürich in Switzerland and recently started his research group in the Hungarian Academia of Sciences. Read more »

Furthermore, FIMM had the privilege of offering a Visiting Professorship to Dr. Mark Daly, Associate Professor at the Massachusetts General Hospital/Harvard Medical School and an Associate Member of the Broad Institute of Harvard and MIT. Mark Daly is a global leader and one of the world’s most often cited scientists in human genetics. Dr. Daly spent June of 2014 at FIMM and will be visiting our Institute on a regular basis during the following years.

In June, the whole Institute gathered for two days for our fifth Annual Scientific Retreat. This time, the theme of the retreat was “From 1000 Genomes to 1: Personal genomes @ FIMM”. Dr. Mark Daly gave an excellent keynote lecture about unravelling the pathology of brain diseases with genetics. The retreat programme also included an interesting session about the Quantified Self with Dr. Rachel Kalmar from Stanford and Misfit wearables presenting.

Panel discussion at the Scientific Retreat.

Predictive, preventive, personalised and participatory

In 2014, FIMM researchers led by Professor Olli Kallioniemi started to plan a new project on system wellness. The Digital Health Revolution project is one of the three new strategic research openings that Tekes, the Finnish Funding Agency for Innovation, funded in June 2014. As defined by Tekes, these strategic research openings are “visionary projects aiming to make serious breakthroughs that will lay foundation for entirely new areas of business in the future”. The goal of the programme is to enable people to utilize data about themselves to facilitate understanding of their health and to engage in health-care interventions and services.

The Digital Health Revolution project aims to combine longitudinal data from different sources about an individual’s state of health. Molecular profiling data (genomics, metabolomics and microbiome), self-monitored health data and other everyday data comprising the personal digital footprint are collected in a systematic way. The programme as a whole is coordinated by the Centre for Health and Technology, University of Oulu. FIMM is responsible for planning and coordinating the pilot projects of wellness research. The first pilot project will start during 2015.

Digital Health Revolution team in a kick-off event in Oulu, August 2014.

In November Olli Kallioniemi invited a pioneer of the systems medicine field, Dr. Leroy Hood from the Institute for Systems Biology in Seattle, to give a lecture in Helsinki. The lecture was the first in the brand new Academic Medical Center Helsinki (AMCH) Distinguished Lecture Series. Before the lecture, the Dean of the Faculty of Medicine and Chair of the Board of FIMM, Professor Risto Renkonen, introduced the new lecture series and the Rector of the University of Helsinki, Professor Jukka Kola, presented the lecture award diploma to Dr. Hood. In his talk, Dr. Hood introduced the P4 medicine concept, 4 Ps meaning predictive, preventive, personalised and participatory. Read more.

Dr. Leroy Hood.

Cracking Research Challenges through Collaboration

Our three Grand Challenge programmes provide an opportunity to align and focus the Institute’s research on large and complex issues. In these projects, researchers, technology experts and clinical collaborators from different FIMM research groups, Technology Centre units and other organizations are drawn together to achieve a common goal through collaboration. All of these three programmes made significant progress during the year 2014.

Finnish Genomes Empowering Personalised and Predictive Health

The Sequencing Initiative Suomi (The SISu) project is an international collaboration between Finnish and international research groups aiming to build tools for genomic medicine. The project is coordinated by FIMM. The aim of the project is to generate, integrate and harmonize whole genome and whole exome sequence data from Finnish samples, many of them produced from population cohorts collected by THL, and provide data resources for the research community. The first version of the SISu-website was officially launched in March, 2014. The website provides an easy access to the genomic variant allele frequency and annotation data for the research community and clinicians in Finland and abroad to perform searches and thus utilize this valuable data resource.

The first version of the data resource is based on 3,000 sequenced Finnish individuals. By the end of 2014, the SISu project has been able to gather data from altogether 5,000 people and the second version of the SISu data resource will soon be released. Collaborations with the Broad Institute of MIT and Harvard and the University of Washington have had a major impact on the number of Finnish samples sequenced. Solely through these collaborations, 10,000 Finns were sequenced last year and 10,000 more will be sequenced in 2015. These collaborations provide opportunities for unique study designs by combining large-scale genome variant data with National Health Register data. In 2014, the SISu project published a proof of principal study, that identified several medically relevant associations to loss of function variants enriched in Finland.

Another important milestone for this Grand Challenge programme was executing the KardioKompassi project. KardioKompassi is FIMM’s first preventative health care pilot project utilizing personal genetic risk information and returning it to the participants. This pilot project was carried out in collaboration with the Finnish Red Cross Blood Services and the Finnish Innovation Fund Sitra. The aim of KardioKompassi project is to study the ways of providing people with health-risk information based on genetic research data, the ways this information is used in preventive healthcare and its usefulness with respect to individual health behaviour. In this project, the transfer of genetic information to an individual’s personal online health account was also being tested for the first time in Finland.

FIMM was responsible for producing the information material for the participants, providing the risk prediction algorithms, performing the genotyping, developing ways to communicate the risk information to the participants, building the IT solutions and applications needed in the project and designing the questionnaires collecting feedback from the participants. Thus, a big team of experts led by Project Director Kari Pitkänen and Dr. Elisabeth Widén worked together the whole year to achieve these goals.

The experience gained during the KardioKompassi project was useful in planning a much larger study concentrating on the same research questions. In June 2014, Tekes decided to fund SalWe’s GET IT DONE programme of personalised diagnostics and care. FIMM is one of the several partners in the programme and the coordinator of the biggest subproject, called GeneRISK Study. Details of the GeneRISK Study were planned during the autumn 2014 and the recruitment of participants started in February 2015. During the next two years, 15,000 individuals will be recruited through Red Cross Blood Service, Mehiläinen Occupational Health Services and Carea (Kymenlaakso Hospital District). Each participant will go through a health check-up to define their risk for cardiovascular diseases, including evaluation of their genomic risk. The results will be returned to participants with couching to lower the risk. Read more.

In addition to the above-mentioned projects, an important opening for FIMM was the funding which United States National Institutes of Health (NIH) provided to a multisite project coordinated by Professor Aarno Palotie and Professor Nelson Freimer (UCLA). The aim of this project is to sequence nearly 4,000 patients with schizophrenia or bipolar disorder to identify genetic variants with a high impact on one or both of these disorders. The project will be launched in 2015.

Individualized Systems Medicine (ISM) in Cancer, AML and beyond

Individual Systems Medicine (ISM) aims to facilitate the care of individual cancer patients by acquiring genomic, molecular and drug-testing data from patient cancer cells and returning such data back to the treating physicians who can then adjust treatment based on individualized recommendations. After patients receive treatment, the response of the cancer cells is measured using genomic profiling, trying to understand cancer response to treatment at the sub-clone level. A unique aspect of the ISM project is the drug sensitivity and resistance testing (DSRT) platform developed at FIMM, which provides in four days dose-response data on 400 cancer drugs directly from patient cells ex vivo. The first publication on ISM was published in 2013.

The most important and fundamental aspect of the ISM Grand Challenge projects has been access to patient samples and data through close collaborations with the clinics, as well as the biobanks and clinical registries. The ISM project in acute myeloid leukaemia (AML) was started at the same time as the foundation was being laid for the Finnish Hematology Register and Biobank (FHRB). In July 2014, the FHRB was registered in the national biobank registry, and was the first national, clinical biobank that received the license to operate. Following in the footsteps of the FHRB, the Helsinki Urological Biobank (HUB) also obtained a license to operate in 2014. Both of these biobanks are important resources and partners for the ISM Grand Challenge.

ISM projects now target other diseases beyond AML, including multiple myeloma, as well as prostate and ovarian cancer. With the growth of these projects, the number of multidisciplinary collaborations has increased at the national and international level. These involve both clinicians and bioinformaticians and have led to funded consortium projects such as the AML Federation involving SAGE bionetworks, Oregon Health & Science University, and others. In addition, the ISM projects have resulted in collaborations with pharmaceutical companies with an idea that by working together on patient-derived material, it will be possible to reposition existing drugs to new indications, as well as to better prioritize new pre-clinical leads for drug development. Indeed, we recently used the DSRT platform to successfully reposition the drug axitinib to target a specific drug-resistant mutant form of the ABL1 kinase in chronic myelogeneous leukaemia and acute lymphoblastic leukaemia. This breakthrough observation opens new opportunities to leukaemia treatment and was published in Nature in early 2015. Overall, these types of collaborative studies with the clinic have made FIMM an attractive partner for research and development projects with the pharmaceutical industry.

Digital Molecular Medicine

Analysis of tissue and cells by microscopy is undergoing a transition from an analog to a digital technology and in parallel allows an increasing number of molecular readouts through multiplexed immunoassays. The paradigm shift from human expert based interpretations to computerized readout has vast implications for both clinical medicine and biomedical research. For example, pathology will change from a mainly descriptive into a more quantitative science and an expert’s decisions will be supported with an array of readouts performed by computer vision algorithms.

Automated computer vision analysis of tumor viability status in human lung cancer xenograft samples. The detected tumorous region is marked with a heat map indicating non-viable (red) and viable (blue) tumor tissue.

Digital Molecular Medicine as one of FIMM’s Grand Challenge programmes has attracted a critical mass of researchers within the field of image informatics, computer vision and digital microscopy. As an example of achievements in this field in 2014, FIMM was the coordinator of the Biobank Technologies Platform within Biocenter Finland that focuses on providing research infrastructure for digital microscopy on a national level. Also, novel technologies developed at FIMM have been transferred to a spinoff company Fimmic Oy that started its operations in 2014 and commercializes information management systems for digital microscopy. In addition, FIMM was awarded Tekes funding to host a FiDiPro Fellowship entitled "Next generation image analysis solutions - towards image-based diagnostics" focused on development of machine learning and image-based readouts. At the end of 2014, FIMM established collaboration with Oxford University that aims to study and develop methods for advanced computer vision analysis of tumour tissue samples.

The digital imaging and readout technologies also create novel solutions for the pharma industry for support of drug development and for novel point-of-care diagnostics. Algorithms that have been developed at FIMM during 2014 include analysis of the tumour microenvironment, detection of cell subtypes and a series of protein expression readout methods. Methods for multiplexed analysis of cell-level protein expression patterns were developed in joint projects with pharma companies. Within the IMI funded PREDECT project on novel models for cancer target validation, FIMM is responsible for the work package on Systems Medicine and handles samples, tissue profiling and web microscopy for the whole consortium. Within the EU funded BioMedBridges project, FIMM has contributed with terminology development for large-scale annotation of digitally scanned tissue samples. In addition, as part of collaboration with Karolinska Institutet in Stockholm a novel man and machine approach was developed for malaria diagnostics, aimed to be used for point-of-care diagnostics together with a mobile microscopy scanner developed in collaboration with Oulu University.

Furthermore, the newly funded Digital Health Revolution Tekes project brings added value to FIMM’s Digital Molecular Medicine Grand Challenge programme by increasing the usability of digital data.

Research