New Capability for Spatial Molecular Imaging at King's College London

In recent years, advances in technology have provided researchers with the opportunity to map the distribution of many molecules simultaneously within a tissue. CosMx Spatial Molecular Imager is one of the newest generation instruments that can for the first time map the location of thousands of molecules at a time within individual cells in a 3D context.
In this proposal, we intend to purchase a CosMx, so that we can use it to enhance our understanding of how individual cells interact with their neighbours and their environment, and how cells organise themselves into tissues and organs. Ultimately, this spatial information will provide insights into biological functions necessary to human life. Our research aims to dig deeper into the study of complex interactions between cells and the way in which their interaction may fail. This will further our knowledge of how humans develop, and how diseases arise and progress. It will help us build better treatments and new therapies, such as those to regenerate lost organ function.

We have circulated a survey to research groups within King's College London to gauge the need for this instrument. Based on the survey's results, 50 academics across 19 departments and 3 faculties will use CosMx to explore over 1000 samples and, in turn,advance healthcare research. By acquiring this instrument and setting up the infrastructure to analyse data from CosMx, we will enable an unrivalled body of knowledge. These projects include the development of new methods for medical research, improving understanding of the interaction between cells, developing knowledge for cancer, cardiovascular and neurodegenerative diseases, as well as identifying new drugs and approaches to regenerate organs and restore their original functionality.

At King's College London, we have established other technologies that are complementary to CosMx. We plan to establish a new facility which will include CosMx, so researchers will be able to easily access it. We will also promote the capability of this state-of-the-art instrument to researchers at King's College London, and throughout the local area of London and SE of England. Our objective is to maximise the benefits of this instrument for the research community. King's College London is highly supportive of this initiative providing a 20% contribution over the cost of instrument acquisition and substantial support for its long term sustainability. Moreover, this acquisition will promote the potential of uniquely qualified post-doctoral fellows and technical and research technical professionals to develop in their careers.

We want to acquire a new capability for spatial molecular imaging at King's College London, to support the large community of researchers relying on spatial biology for their cellular and molecular medicine research. In particular, we plan to acquire a nanoString CosMx Spatial Molecular Imager. This instrument combines the power of high-multiplex profiling with high-resolution imaging to analyse up to one thousand RNAs or one hundred proteins within single cells in morphologically intact tissue samples. The technology is based on highly multiplexed in-situ hybridisation. RNA or protein targets are identified through hybridisation with base-paired probes or antibodies labelled with unique barcodes, followed by barcode readout with rounds of fluorescent probe imaging. Each RNA or protein appears as a single spot and is digitally quantified by counting the number of imaged spots. The encoding scheme has 64-bit (4-colors X 16 cycles) that assign 1020 codes allowing error detection and correction, yielding high accuracy and sensitivity. The chemistry involves no reverse transcription or amplification for high detection efficiency and unbiased quantification. The platform is capable of profiling RNA and protein down to sub-cellular levels in cell samples and multiple tissue types, including formalin-fixed paraffin-embedded and fresh frozen samples. The instrument allows direct use of pathology lab-standard glass slides.

CosMx is accompanied by the AtoMx cloud data storage and analysis software with an intuitive interface. Its data analyses include modules for QC normalisation, dimension reduction, UMAP/tSNE calculation and visualisation, cell typing (with marker identification), and spatial clustering (HMRF specific type). Additional modules are available for differential expression, cell proximity, signalling pathway analysis, ligand-receptor co-expression, and protein data analysis. Integration of user-designed modules and newly developed tools are supported.