Saka Group

Spatial biology from molecules to tissues: high-dimensional investigation of cellular organisation

The Saka group develops new tools and methods to investigate the spatial and molecular organisation of cells across scales. The group harnesses new labelling approaches; fluorescence, super-resolution, and correlative microscopy methods; and DNA nanotechnology.


Previous and current research

We aim to understand the spatial features and organisational principles of biological structures ranging from nanoscale complexes to subcellular compartments, cells, and tissues. To enable comprehensive investigation, we develop molecular tools and methods for conventional and super-resolution imaging, and employ multimodal approaches.

Previously, we have combined metabolic labelling, bioorthogonal click chemistry, cell fusion assays, and super-resolution microscopy to understand the universal principles of protein organisation in cellular membranes. We have also developed a correlative optical and isotopic super-resolution imaging modality (COIN) that makes it possible to study the turnover of proteins in subcellular compartments of neurons.

Recently, we have harnessed the barcoding capacity and programmability of DNA to generate powerful tools for single-molecule imaging and multiplexed detection of proteins and nucleic acids in cells and tissues. We are expanding and applying these tools to visualise the spatial organisation and heterogeneity of subcellular structures and organelles.

To broaden DNA-based detection further to the tissue scale, we have developed a new signal amplification method called signal amplification by exchange reaction (SABER) for immunofluorescence (Immuno-SABER) and fluorescence in situ hybridisation (SABER-FISH) to enable high-throughput multiplexed profiling of single cells in their native tissues. We are currently using SABER to reveal the spatial features of cellular functions in human tissues.

Future projects and goals

  • We will expand our technology suite by:
    • Building a high-throughput single-cell platform for spatial multi-omic profiling of cell states, utilising integrated imaging, sequencing, and machine learning.
    • Developing new correlative and multimodal imaging workflows for comprehensive profiling of cellular phenotypes.
  • We will establish new reporters and approaches to probe and modulate the organisation of organelles and membraneless assemblies and investigate how biomolecular condensates intertwine with the molecular cell state and the cell’s response to stress factors.
  • We aim to apply these approaches to address the fundamental question of how single-cell identity relates to spatial and molecular organisation. These efforts will help to uncover the complexity of intricate diseases like cancers and neurodegeneration at the single-cell level, and will provide new insights into cellular homeostasis, disease formation, and drug response.
Figure 1: Illustration of the Immuno-SABER approach for multiplexed signal amplification using DNA-barcoded antibodies. Here, Immuno-SABER is applied to enable 10-colour imaging of marker proteins with high sensitivity in mouse retina sections.
Figure 2: Multiparametric investigation of cell state by integrating spatial information, subcellular morphology, and molecular make-up of cells. This enables us to understand how cells respond to perturbations and disease factors.