We continuously strengthen our research infrastructures by developing and implementing novel methods and technologies, upgrading key equipment and setting up new core units in areas lacking services. The range of available research infrastructures is one of FIMM’s key strengths and we work with research groups to integrate multiple technologies to create more exciting research projects whenever possible. FIMM Technology Centre is open to method development proposals from research groups, hospitals, and commercial customers and works on ‘first come, first served’ basis. Priority will be given to requests that aligns with the Institute’s research focus. Below we list some of our ongoing R&D activities.
Working closely with FIMM cancer researchers, FIMM Technology Centre experts have developed workflows and analytical pipelines for ex vivo drug testing of patient cells, allowing for rapid feedback of clinically relevant information to the clinic, and at the same time deeper insight in the molecular drivers of the disease. For example, exome sequence data from tumours is analyzed to identify somatic cancer-driving mutations, while drug sensitivity and resistance testing (DSRT) data are used to develop methods and models to identify selective and synergistic drug combinations.
The core of DSRT is the unique in-house built compound library with >500 approved and investigational oncology-related drugs and probes, readily available as such or as a subset of much wider combinatorial and customized drug panels. Viability and cytotoxicity tests were the original readouts for the drug efficacies. Recently, we launched the first DSRT service based on flow cytometry readout, targeted to AML samples (optimized antibody panel, compound set and data analysis pipeline), which allows to characterize drug responses of individual subpopulations within a complex cell mixture. High-content imaging -based readout for DSRT at single cell level is also available and can be applied in visualization of drug effects e.g. on cancer organoids in 3D. The DSRT data from all readouts can be analysed in an automated manner using the in-house analytics pipeline Breeze.
FIMM has a key technical and scientific role in developing clinical sequencing applications. Our Genomics Unit formed a partnership with HUS in 2019 in order to deliver state-of-the-art diagnostics. The jointly led HUSGEN has received accreditation for clinical WES service. Next, the lab will accredit clinical WGS and RNA-seq services.
FIMM Digital Microscopy and Molecular Pathology Unit and High Content Imaging and Analysis units are developing automated machine learning approaches for image analysis of digitized tissue and cell samples and clinical informatics tools to enable and promote translational research.
Recently, FIMM Digital Microscopy and Molecular Pathology unit has included a multiplexed immunohistochemical (IHC) and immunofluorescence assay for tissue staining and imaging allowing seven-marker detection using fluorescence into the service pipeline.
The impact of single cell technologies for science is going to be huge. Single cell analysis methods will be very important approaches on many levels of biomedical research from basic research to personalized medicine.
One example of method development within this area is Computer Assisted Microscopy Isolation, which combines image analysis algorithms, machine-learning, and high-throughput microscopy to recognize individual cells in suspensions or tissue and automatically guide extraction through laser-capture microdissection or micromanipulation. In early 2020, we have set up the phenotypic isolation of single cells in primary cultures or of multiplexed stained cancer tissues. These isolated cells can further be analysed e.g. with single cell transcriptomics and the data combined with the known spatial context of cells. This is an ongoing academic collaboration between research groups and FIMM High Content Imaging and Analysis Unit and Single-Cell Analytics unit.
Single-cell Analytics unit has also joint efforts with research groups involved in microfluidics and chip fabrication. The aim is to develop new high throughput single cell assay platforms based on customized chips with thousands of wells per microscope slide tailor made for cellenONE F1.4 single cell dispenser, which is superior in accuracy dispensing only one cell per one well and is the instrument of choice when cell number for the experiment is limited.
Many sequencing -based genomics and transcriptomics applications are already commonplace techniques but the diversity and sophistication of cutting-edge methods is ever developing. The trend in customer requests is towards challenging and sophisticated techniques and accompanying bioinformatic analysis. To meet the demand of the user base FIMM Genomics has built and will continue to develop services for cutting-edge medical NGS technologies such as low-input transcriptomics, ultra-deep tumor sequencing and cell free DNA analysis from liquid biopsies.
Metabolomics Unit is setting up a national fluxomics service in support of biomedical research. The analysis uses quantitative metabolomic data and isotopic labelling measurements to reconstruct metabolic networks that describe the rate of metabolic reactions. Fluxomics is an important application in e.g. cancer and mitochondrial disease research and computation-heavy. We will work in close partnership with the Finnish ELIXIR node at CSC on workflow standardization.