Dr. Pirkko Mattila is the Head of the Single-Cell Analytics (SCA) Unit, a research infrastructure at the Institute for Molecular Medicine Finland (FIMM), offering cutting-edge single-cell sequencing and spatial transcriptomics technologies as services for researchers. 

With the technologies offered by the SCA Unit, researchers can ask scientific questions about cell population heterogeneity based on gene expression, immune profiling, chromatin structure, and nucleotide or copy-number variation, all at single-cell resolution. In addition, multi-omics data integration, single-cell bioinformatics, and dispensing of single cells are supported. Dr. Mattila gives an example:

We have been providing services for and collaborating with the FIMM Grand Challenge Program in Functional Precision Medicine for Cancer, mainly with Dr. Caroline Heckman´s group and acute myeloid leukemia studies. Hematological samples are optimal for single-cell analysis on the 10X Genomics Chromium platform, because the blood cells are in suspension and no dissociation of the tissue is needed. 

She continues: 

We can study populations of cells before and after cancer treatment, looking at how the populations change. We analyze the transcriptome in each of the cells, and cluster the cells based on their transcriptomes. Similar cell types have similar transcriptomes. Before treatment, you can see the blast cells, the cancer cells. And after the treatment, if it's successful, the population of blasts has disappeared or is much smaller. 

As with all life science technologies, challenges do arise. For example, initially single-cell sequencing demanded live cells, making long-distance cooperation difficult.  However, “nowadays, we can also use fixed cells, a side of the technology that has been developing quickly,” says Dr. Mattila.

Furthermore, not all samples contain cells in suspension. Dr. Mattila explains:

We also do a lot of single-cell analysis with solid tissues. We advise on tissue dissociation protocols for researchers, so that we have a cell suspension. This is not as optimal as for blood cells, because there are always changes in transcriptomes when tissues have been dissociated. In addition, some cell types are more fragile than others. 

New advances in spatial transcriptomics may also help to overcome some of the challenges presented by solid tissue samples. 

Recent advances in spatial transcriptomics

A little over a year ago, the SCA Unit began investing in a new molecular profiling technology called spatial transcriptomics. This ground-breaking approach enables both the measurement of gene activity as well as the mapping of that activity in tissue samples. Dr. Mattila explains: 

Spatial transcriptomics is high resolution RNA-sequencing merged with imaging. In traditional single-cell technologies, we analyze cells in suspension. But with spatial transcriptomics we use tissue sections and visualize the RNA content at single-cell or near single-cell resolution, to examine cells in the context of their neighbors.  

There are primarily two widely used commercial platforms for spatial transcriptomics - the Visium platform by 10X Genomics and the GeoMx Digital Spatial Profiler by NanoString. The 10X Genomics platform has been in operation in the SCA Unit for about a year, and the NanoString GeoMx is slated to be installed in March 2022, expanding the capacity for single-cell applications in the unit. Of these two platforms. Visium is best suited for discovery work and GeoMX DSP for targeted research questions. Researchers are already lined up waiting to apply the technology to their projects. Teijo Pellinen, a senior scientist at FIMM gives an example:

We expect to discover spatial dependencies on the expression of tumor microenvironment-associated gene transcripts, such as those expressed by fibroblasts and immune cells. For this, we will analyze tumor stroma regions located close to and distant to tumor epithelial areas with distinct gene mutations. These experiments will thus reveal interesting and novel biology between genetic mutations and the tumor microenvironment.

A collaborative team atmosphere

The SCA Unit is part of the FIMM Technology Centre, providing

an optimal environment for implementation and development of novel single cell technologies, because all the SCA workflows depend on existing services and skills in other Technology Centre units like IT, Digital Microscopy and Molecular Pathology, HIPREP (nucleic acid isolation), and importantly, Sequencing. This arrangement makes for a strong, active, and convenient collaboration among the units, 

explains Dr. Mattila.

As head of the SCA Unit, Dr. Mattila is responsible for funding, recruitment, and strategic planning. All of the project work is carried out by the other members of the SCA team. Dr. Mattila describes the roles:

My role is possible only because we have an excellent team of talented and dedicated staff in the unit. Jenni Lahtela is the SCA Project Coordinator with operational leadership. Then we also have, Bishwa Ghimire a bioinformatician and Emma Saarinen an NGS (next generation sequencing) expert, both sharing  their time between the SCA and NGS. And, Anna Näätänen, the SCA Laboratory Coordinator, is involved in customer contacts and running the Chromium and Connect 10XGenomics instruments. 

In addition, considering the new and growing investment in spatial transcriptomics, the Unit recently recruited Anette Holmström to join the team and dedicate half of her working hours to this exciting development for users. 

Dr. Mattila’s time is also devoted to the “ordinary” bulk RNA-sequencing transcriptomics in the Genomics Unit of the FIMM Technology Centre. This is a rapidly growing service, especially considering the involvement in the iCAN Digital Precision Cancer Medicine Flagship project in Finland where they have also begun to work with customers in international pharmaceutical companies: 

The iCAN flagship is a large national project in precision cancer medicine and digital health. Our role is primarily in RNA and exome sequencing. But, there is also a category of analyses in the project called deep profiling, which will also include, single-cell analysis. So, I'm expecting to have an increase in the numbers of users through iCAN soon. Both to spatial transcriptomics and traditional single-cell analysis.

Dr. Mattila considers herself fortunate to work with the SCA team and emphasizes the rich and productive environment they all create, “I know that our success is a result of the teamwork and great atmosphere in the unit. It's really the base of all. We couldn't manage otherwise, because in both Genomics and SCA, we have far more things to do than we have hands or brains for.”

With the fast pace and high impact work in the unit, teamwork isn’t essential from just the practical standpoint. It also becomes the motivation to run the facility and to deliver on the multitude of projects. According to Dr. Mattila, “if you have a good atmosphere, the result is better because you are feeling good, and you have mates to discuss with and the experience of real teamwork.”

Simply put: “teamwork is the best kind of work.”

Stoking interests in a career in genomics

Genomics has been an integral part of Dr. Mattila’s scientific career since her PhD at the University of Helsinki in the mid-90s, alighting a fascination in gene expression:

I have always been interested in genomics, namely transcriptomics, the RNA side. I have found it fascinating how cells react to their environments by modifying their gene expression. And the diversity of different types of RNA molecules with various functionalities is quite amazing. The preciseness of sequencing technologies, akin to digitizing nucleic acid, is more black and white than other technologies.

Dr. Mattila traces her intrigue back some 20 years to two significant events in the history of science:

Two occasions, both in the early 2000s, had a profound impact on driving me forward in genomics. The first, around 2001, is when the concept of systems biology took off. For several years the topic was discussed at a very high-level topic in conferences. And the other one, a couple years later, was the Human Genome Project, which finished at that time. I won't ever forget my astonishment when it was determined that humans only have about 20,000 genes, the same as in mice and rats!

Out of this passion has grown what she sees as her most rewarding professional accomplishment – the establishment of a single-cell analytics unit at an international research and technology center: ‘Single-cell genomics’ has always been mostly about transcriptomics. So, it was very natural to establish this unit, right after knowing that the technologies in single cell resolution are ready. So, I think it has been the most rewarding, if not also most laborious, project of my career so far.” 

With her close colleagues in Helsinki, Dr. Mattila also tries to pass the torch and spark interest in genomics in Master’s students: “each year, we teach in a Principles in Bioscience Omics course. I coordinate the 2-week module on genomics, epigenomics and transcriptomics, including single-cell analytics.” 

The SCA unit also organizes one to two hands-on courses for PhD students in single-cell technologies each year. While teaching has not been the primary role of the Unit, it has been an important way for the unit to inform the junior research community about the theory and practical applications of transcriptomics for the past several years. 

Single-cell analytics for your research project

The Single-Cell Analytics Unit provides academic researchers access to state-of-the-art instruments and outstanding training and project support, positioning Finland on the global research infrastructure map in life sciences in single-cell technologies. The Unit welcomes new users and project inquiries.

Thanks to continued funding from the Academy of Finland, the Unit has been able to make infrastructure investments to stay at the forefront of single-cell technologies for the local, national and international academic research community. Dr. Mattila’s team will soon launch the NanoString GeoMx platform, expanding capacity for spatial transcriptomics: 

“Thanks to the Academy of Finland national research infrastructure investment the newest platform from NanoString can be offered by us in Helsinki as well as by a group in Turku, Finland. The system will be installed in March 2022 and training will take place within a month. Users are already lined up!”

The Unit both provides services and establishes research collaborations that involve deeper developmental work than the routine services. Both are supported through user fees. Unit staff are able to assist and advise on the project workflow. Support for on-site visits may be available for researchers within the Nordic EMBL Partnership through the NordForsk Infrastructure Hub Grant. For more information on support for mobility within the Nordic EMBL Partnership, please contact your local administration.

Researchers interested in utilizing single-cell technologies are welcome to contact the Single-Cell Analytics Unit at FIMM by sending an email inquiry to Jenni Lahtela (jenni.lahtela(at)helsinki.fi).
 

The “Technologies Advancing Molecular Medicine” series highlights the people and activities in research technologies and core facilities in the Nordic EMBL Partnership for Molecular Medicine.