Grand Challenge programmes

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 organisations are drawn together to achieve a common goal through collaboration.

Finnish Genomes Empowering Personalised and Predictive Health

In 2015, human genomics at FIMM achieved substantial progress in many areas. The past year was successful both in terms of establishing outstanding public-private partnerships, receiving international funding and initiating several large sample collection projects. Furthermore, FIMM researchers responded to the growing need of new type of expertise among the future physicians by organising the first course on personalised medicine in collaboration with the Faculty of Medicine and Sitra.

Attractive combination of Finnish genome and health information

The Sequencing Initiative Suomi (The SISu) project coordinated by FIMM is an international collaboration between Finnish and international research groups aiming to build tools for genomic medicine. 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 and Finnish clinicians. In 2015, we were happy to announce a new release of the SISu data resource. The project website and the search function were also completely renewed. The new features allow users to get a more comprehensive picture of all the possible genetic variation, regardless of the quality of the sequence data. In addition, the users now have a possibility to filter the results based on enrichment in the Finnish population. The current release is based on 6,100 whole exome sequenced Finnish individuals from ten different cohorts. Many more have already been sequenced through collaborations with the Broad Institute of MIT and Harvard and Washington University and harmonizing the sequence data is ongoing. Read more.

The Sequencing Initiative Suomi (SISu) project website.

The collaboration between FIMM, THL and Broad Institute provides opportunities for unique study designs by combining large-scale genome variant data with national health register data. This unique combination is attractive also in the eyes of pharmaceutical industry. During the spring 2015, FIMM’s Research Director Aarno Palotie made a major effort to coordinate contract negotiations between four international pharmaceutical companies, THL biobank, Broad Institute and FIMM. All the parties entered into a research collaboration in June 2015, marking a beginning of a very unique collaborative endeavour. Compatible with the objectives of the Genome Strategy of Finland, the project aims to make use of the existing genetic variations in the human population to identify specific causes of disease and to utilize this information to achieve faster and more predictable development of new drugs. During the autumn 2015, the FIMM research team has built pipelines for efficient lookups for downstream health effects of interesting genetic variants. FIMM also decided to implement technology developed by a Finnish bioinformatics company BC Platforms to enhance storing of the data.

New FIMM coordinated sample collections cover both illness and wellness

The year 2015 saw also the launch of several big sample collections and high-profile research projects. Recruitment of participants in the FIMM coordinated GeneRISK Study, the biggest subproject of a Tekes funded SalWe’s GET IT DONE programme of personalised diagnostics and care, was initiated. In this unique study, strengths of several health care actors representing both academia, public and private healthcare sector and civic organisation are combined. Nearly 3,000 45-65 year old citizens were recruited through Carea (Kymenlaakso Hospital District), Red Cross Blood Service and Mehiläinen Occupational Health Service by the end of the year and the recruitment is estimated to continue until spring 2017. Each participant goes through a health check-up to define their risk for cardiovascular diseases, including evaluation of their genomic risk. The results are then returned to participants through an upgraded KardioKompassi web-portal with couching to lower the risk. The GeneRISK Study is led by Group Leader Elisabeth Widén and Professor Samuli Ripatti. Read more.

New layout of the KardioKompassi web-portal.

In August, we were proud to announce our role in the international Stanley Global Neuropsychiatric Genomics Initiative, an ambitious collaborative project, aiming to collect up to 50,000 samples from schizophrenia patients across the globe. This project, led by The Stanley Center for Psychiatric Research at Broad Institute, is enabled by a generous philanthropic commitment from Ted Stanley. The collection aims to address the current lack of suitable large sample collections in the field of psychiatric genetic research. The Finnish part of the project, named SUPER study, is led by Professor Aarno Palotie. Finland is the European pilot country of the Stanley Global Initiative and the aim is to collect a minimum of 10,000 samples from psychosis patients. The study was commenced with pilots in Oulu, Tampere and Kuopio regions in the autumn of 2015. The national study will be launched in early 2016 and will continue for three years.

In addition to these disease-oriented sample collections, FIMM’s first systems wellness study, the Digital Health Revolution project pilot study funded by TEKES, was kicked off in 2015. Around a hundred participants were recruited in the study in early autumn. Each participant will receive a deep next generation systems wellness health check-up every four months. Physiological, genomic, clinical chemistry, metabolomics, proteomics, gut microbiome and comprehensive life-style data is systematically collected and monitored during the 16-month study period and key data is provided to the participants, together with personalised wellness and lifestyle advice and coaching. Changes in participants’ health, wellness and risks for complex diseases, as well as in their behaviour and attitudes towards receiving deep health and wellness data and coaching are monitored. The project is led by Professor Olli Kallioniemi.

Enabling Precision Medicine for Cancer

While the president of the United States only announced in 2015 a Precision Medicine Initiative using an approach taking into account individual differences, researchers at FIMM along with colleagues at Helsinki University Hospital Comprehensive Cancer Center (HUS) and its hematology department, as well as other hospitals in Finland have been working together on the Individualized Systems Medicine (ISM) grand challenge project since 2010. The program aims to improve treatment decision and outcome for cancer patients by applying technology platforms, including ex vivo sensitivity and resistance assessment of patient tumour cells against hundreds of different inhibitors, along with deep molecular profiling, with rapid results to determine and adjust treatment.

The initial focus of the ISM program on acute myeloid leukeamia (AML) continues to expand, but the project framework has been adapted to other hematological malignancies. Several new drugs have been recently approved or are in late stage development for different blood cancers, thus treatment decisions will become more challenging just based on the availability of a wide selection of new therapy options. However, markers predicting response are still lacking and the pharmaceutical industry has recognized the need to better identify patients that will respond to their drugs.

Together with HUS and the Finnish Hematology Registry and Biobank (FHRB), FIMM researchers are now collaborating with pharmaceutical industry partners assessing the efficacy of preclinical compounds on patient samples to identify promising therapies and responding patient groups. This is exemplified by a collaboration initiated in 2013 with the US company Celgene, which originally started as a feasibility study in multiple myeloma, but during 2015 expanded to an extensive preclinical project with substantial funding using the ISM framework to identify novel treatments for both and leukeamia. Although the collaboration has directly benefited FIMM research efforts, long-term gains to healthcare in Finland are also being realized with approved phase I/II clinical studies coordinated from HUS. In addition, the hospitals are utilizing the results to make more informed treatment decisions on costly drugs and avoiding toxic, ineffective treatments.

During 2015, research collaborations were also established with Pfizer and more recently Bayer. The collaborations, however, have not been limited to the pharmaceutical industry. The ISM program includes technology development, with a recent collaboration established with the US company Intellicyt, to develop and apply their high throughput flow cytometry instruments for drug sensitivity assessment and precision medicine efforts. Collaboration with Labcyte, a US biotechnology company manufacturing acoustic liquid handling systems, was also extended.

Application of the ISM program to other disease indications, particularly to solid tumours, will lead to other collaborations. Current efforts in ovarian cancer are growing and precision medicine for urological cancers is a major focus at FIMM. All of these projects will continue to attract international investment opportunities and promote FIMM and Finland to the global forefront of precision medicine research.

Renal cancer patient-derived cell culture.

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 on 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.

Digital Molecular Medicine as one of FIMM’s Grand Challenge programs 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 2015, 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. At the beginning of 2015, FIMM established a collaboration project with Oxford University that aims to study and develop methods for advanced computer vision analysis of tumour tissue samples, with focus on urological and breast cancer.

The digital imaging and readout technologies create novel solutions for the pharmaceutical industry for early phase drug development within oncology and for novel point-of-care diagnostics. Algorithms that have been developed at FIMM during 2015 include analysis of the tumour microenvironment, detection of cell subtypes, especially immune cells, cancer tissue viability classifiers, and a series of protein expression readout methods. During 2015, methods for analysing multiple antigens in the same tissue section, i.e. multiplexed immunohistochemistry, have been further developed. Multiplexed immunohistochemistry provides a powerful approach in combination with digital image analysis, allowing robust segmentation of specific subpopulations of cells and compartments of tissue (e.g. detection of epithelium by using epithelial proteins to assist the segmentation). Currently, our system can detect up to six different protein markers and nuclei in a single tissue section. Methods for multiplexed analysis of cell-level protein expression patterns were utilized in joint projects with pharmaceutical companies in 2015. 

Multiplexed fluorescent staining of human prostate cancer tissue, showing cancer glands in red and green, and one normal epithelial gland with pink cell lining.

The progress of precision medicine projects at FIMM has increased the need for tailored high-content image analysis methods, e.g. to study tumour heterogeneity, both at a cell and tissue level. The ongoing TEKES FiDiPro fellow project "Next generation image analysis solutions - towards image-based diagnostics” focuses on finding computational solutions for disease phenotyping at single cell level. The additional imaging tools have also been developed at the Systems Microscopy Network of Excellence (EU FP7). These projects together have enabled, e.g. the translational approaches for phenotypic exploration of reactivity of patient –derived cancer cells towards specific drugs. Both the academic and industry partners have applied the generated tools in collaborative projects during 2015.

The recently founded FIMM Imaging Expert Group had several meetings during 2015, and thus empowered the exchange of know-how related to image analysis within the FIMM community. As part of the IMI funded PREDECT/ENSO project on novel models for cancer target validation, FIMM has been responsible for the work package on Systems Medicine for handling samples, tissue profiling and web microscopy, as well as results read-outs for the entire consortium, including tens of thousands of samples. Within the EU funded BioMedBridges project, FIMM has contributed with terminology development for large-scale annotation of digitally scanned tissue samples. Also, a project based on innovations at FIMM related to mobile microscopy received funding from both Tekes and Vetenskaprådet in Sweden in 2015. In collaboration with Helsinki Innovation Services and Karolinska Institutet in Stockholm, clinical studies on the use of mobile microscopy for point-of-care diagnostics will be started in 2016.

Grand Challenge Programmes