Leah Officer-Jones, Histopathology Technology Manager at CRUK Scotland Institute, explains the challenges of working at the cutting edge of discovery. Its vital researchers can process and explore the huge amount of data generated by the latest in situ technologies.
What are the biggest challenges you face with new lab technology?
Over the last decade in situ technologies have progressed from visualising one protein or one gene per slide to hundreds or even thousands. With these exciting developments in technology, we are able to visualise cell to cell interactions in the tumour microenvironment, leading to new discoveries. Creating these higher plex assays is complicated, and the more layers you add the more technically challenging it becomes. Validation and checking that all those antibodies work as expected on the tissue without introducing artefact can be time-consuming and difficult. This has led to a new highly specialised technical role.
The increase in assay complexity means the volume of data that is generated from one slide becomes huge. A single tissue section can produce hundreds or even thousands of layers of data that can be complex to understand, process and manage. The interpretation of this data presents a new challenge for researchers and bioinformaticians.
The increase in complexity and data also means it can be more time-consuming to perform tests, which results in a lower throughput, but also a larger equipment footprint. With routine immunohistochemistry you could stain hundreds of slides a week, and with higher plex platforms you may be limited to two slides a week. The only way to increase the throughput of these assays is to increase the volume of instruments. We therefore work closely with researchers to ensure the samples they select for these assays will generate the highest quality data possible.
On the one hand, new technologies mean that you can get much more data from tissue samples. However, each new instrument has unique data and technical challenges.
Can there be such a thing as too much data?
There's been so much excitement about the multiplex imaging of RNA and protein.
A lot of people have generated huge data sets, which present a data challenge – and they don't really know what to do next. We are now in a position where we can generate more data from a single tissue section than ever before. These technologies are still emerging, and there isn’t currently a universal approach for analysing spatial data, or combining data from multiple platforms. The bioinformaticians in our institute are continually developing new methods to answer questions with these large new datasets.
The data sets change rapidly as the technology continues to develop. One month, it might just be protein, and then the next month, there's a new technology which combines protein with RNA, or we may run two or three experiments on the same slide. We have to invest a lot of time in maintaining our skills and knowledge to keep up with these new assays and emerging technologies, which we do as individuals and as a team.
What do you think will be the biggest challenges in medical and pharmaceutical research in 2025 (and beyond)?
The more complex experiments get, the more expensive they are. As a result, we have to apply for external funding to actually do those experiments, or to expand our service. This can be challenging and competitive.
Throughput is also a challenge because the more plex we have, the slower it is. It is therefore essential that we pick the most informative samples for the most costly, complex, and low throughput methods. Tissue micro arrays are an invaluable tool for generating data from multiple samples on one slide.
We also face challenges in combining and integrating different technologies. We’re seeing scientists want to combine more technologies into one tissue section rather than just using one technology to generate data from both spatial proteomics and spatial transcriptomics within the same cell, for example, rather than using serial sections.
I’m sure a new technology will emerge that we don't know about yet, we work in a rapidly changing field.
What are the challenges of introducing new technology into the lab?
It can be difficult to accommodate the diversity of new platforms as they are released. We have to grow our team, and as individuals, we need to broaden our expertise.
We often find that when a new technology arrives, we need to spend a significant amount of time validating the instrument, workflows, and training expert staff. It also takes time to get to grips with the data. We hope that new technology will arrive and be up and running within six months, but in some cases, it can take up to two years to validate and generate robust reproducible pipelines.
One major challenge is uptake. We have these new exciting technologies, but it takes a while for them to find their place. One of our roles is to offer advice on the most appropriate technologies and to guide people to the assay that will best answer their questions.
Roche Research Solutions
Advancing research and empowering discoveries
Roche provides researchers with leading innovations for genome sequencing, tissue staining, microarray analysis, nucleic acid purification, cell analysis and real-time qPCR. Working with you, we’ll streamline implementation and accelerate discovery in your lab.