DDW Editor Reece Armstrong speaks to Ellie Mahjubi, Vice President, Protein and cell analysis at Thermo Fisher Scientific, about how spatial biology is impacting drug discovery and development research.  

RA: What’s the future and potential for spatial biology? 

EM: Technological advancements in spatial biology are providing unprecedented insights into single cells within their spatial context, facilitating the analysis of cell types, functional states, cell interaction networks, as well as tissue microenvironments and architecture. These innovations promise to significantly advance basic research and enhance our understanding of human health and disease. 

While the current emphasis is on proteomics and transcriptomics, emerging applications such as epigenomics and metabolomics are gaining traction. Progress in machine learning and artificial intelligence is expected to streamline data analysis and interpretation, particularly in integrating high-dimensional multi-omic datasets. As the field progresses, improved technologies and reduced costs will likely drive more widespread adoption in both research and clinical settings, paralleling the trajectory observed in the genomics field. 

RA: How does automation accelerate the spatial biology research? 

EM: Spatial biology experiments have many time-consuming and tedious steps. Automation saves researchers time by performing manual work, creating more opportunities to study additional tissue samples, collect further data and interpret results. Automation can even help alleviate the number of manual errors that can be introduced with too many steps or reagents in an experiment.  

Large data sets come with some downsides. Even without automation, spatial biology experiments generate a considerable amount of data, often with much more complex parameters than single cell-ribo nucleic acid (RNA) sequencing (scRNA-seq) or traditional next generation sequencing (NGS). The extensive volume and intricate nature of the information involved in spatial biology will require more robust data management, computing power and analytical programs capable of extracting features and generating quantitative data for spatial analysis. This challenge becomes even more pronounced within automated environments. 

RA: In terms of disease focus, does spatial biology lend itself better to something such as cancer?  

EM: This powerful technology can be used to study many diseases. However, not surprisingly, we are seeing the greatest adoption in cancer. Immuno-oncology and the ability to harness the immune system to destroy cancer cells has been a literally life-changing development in the treatment of cancer. Detailed analysis of the tumour microenvironment and the interaction between cancer cells and other cell types, particularly immune cells, cannot be accomplished by bulk tumour tissue analysis or by the analysis of dissociated single cells. Spatial information is essential.  

Furthermore, these methods can work on common sample types, such as formalin-fixed paraffin-embedded (FFPE) cancer tissue. Immunohistochemistry and digital pathology are commonly used in the cancer field, but generally focus on H&E staining and/or detection of one or a few markers. The ability to study more markers is the next logical step and will also aid in precision medicine by identifying unique patterns or signatures in a patient’s own tumour. 

RA: Do you expect spatial biology approaches to overtake single-cell studies and cell culturing, or will there be applications for both aspects of research?  

EM: Single-cell studies or bulk analysis will always have a place. Techniques including flow cytometry may not retain structural information, but they are well established and show cell populations in a relatively short amount of time. Right now, we have ample data that details what goes on in individual cell populations. Spatial biology is needed to understand what is occurring with cell populations within tissues and organs. Researchers have recognised this need and are evaluating spatial biology platforms to run their experiments. Greater adoption of spatial biology techniques will evolve as platform and reagents decrease in costs and complexity.  

RA: How transformative can spatial biology be for drug discovery? Do you anticipate any major advances in treatments due to research using spatial biology.  

EM: The extensive data derived from spatial transcriptomics and proteomics can provide a novel perspective on disease complexity and serve as a valuable tool for drug discovery researchers. This includes elucidating disease mechanisms, identifying and validating new drug targets, and discovering biomarkers to predict drug response or monitor disease progression. The insights gained hold the promise of driving precision medicine by offering personalised insights into disease. 

RA: How accessible is spatial biology to teams with smaller resources and budgets?  

EM: The field is expanding as more affordable platforms and reagents become available. Open methods and analysis programs, which can be utilised on existing equipment, are also accessible, though they often require more manual effort. Researchers with limited budgets or those undertaking short-term projects can access platforms and technologies through core facilities or spatial service providers. Additionally, they can leverage publicly available datasets shared by the spatial community for their research endeavours. 

RA: What other technologies can be used alongside spatial biology to improve our understanding of drug targets, discover new biomarkers et?  

EM: Initial discoveries made through spatial approaches can be validated and further explored using more traditional methods, similar to how functional genomics complements findings from next-generation sequencing (NGS) experiments. Real-time dynamics are challenging to monitor with tissue samples, as they represent only a cross-section of space and time. Researchers can also utilise more complex in vitro models that replicate microenvironments, such as three-dimensional cell culture structures. Additionally, employing CRISPR technology to perturb genes within these models can help identify and confirm mechanisms, or determine if a similar phenotype is observed with gene knockout compared to drug intervention. 

RA: What most excites you about spatial biology? 

EM: Spatial biology enables the research community to enter uncharted territory and make new discoveries regarding human health and disease. It is very exciting to see the increasing adoption and impact of spatial biology, the highly interactive community that is developing, as well as the collaboration and partnerships that are driving the field forward, including academia, pharma and biotech sectors.    

One powerful example is the contribution of spatial data to the ongoing development of the Human Reference Atlas (HRA), which is a high-resolution, high-content three-dimensional representation of the healthy human body. This ambitious undertaking is a truly collaborative effort by the Human BioMolecular Atlas Program and numerous other consortia and has been described as a “Google Map” of the human body. 

RA: What are some of the biggest challenges within the field? 

EM: New technologies often come with significant costs and time commitments. The manual effort involved in developing higher complexity experiments require extensive planning, thorough testing, and intensive data analysis, which collectively impose a substantial burden. 

For protein profiling, another challenge is having access to validated antibodies and the cost and time that goes into panel development, as researchers expand into a variety of targets and research areas that will cover more of the proteome. 

As a life science company, it is essential to lower the barrier to entry and democratise spatial biology to advance the field. 

Biography  

Ellie Mahjubi is Vice President of Protein Cell Analysis at Thermo Fisher Scientific. With past leadership experience at Corning Life Sciences and GE Healthcare, her leadership expertise is in genomics, proteomics, and cellular analysis technologies. She holds degrees in biochemistry, life sciences management, and an MBA in technology management.