Worm Expansion Sequencing (WormSeq) as a Scalable Tool for Molecularly Annotated Connectome (MAC)

Expansion Sequencing (ExSeq) ¹ is an innovative technology that can reveal molecular signatures at an unprescendented details and complexity. It has subcellular nanoscale resolution, retains the spatial information and has high multiplexed capabilities that allow interrogation of hundreds and thousands of genes together with other information modalities such as lipid, sugar, proteins, all in one biological context. Its combination with the recently published Expansion Microscopy-based connectomics protocol will greatly enrich the information content of traditional connectome. In fact, molecularly annotated connectome (MAC) has been long thought of as a critical missing pieces for understanding how the wiring diagram gives rise to behaviors. I am currently developing the protocol to generate the world’s first MAC. This project, which I call WormSeq, will form the necessary building block for simulating the C. elegans nervous system with high biological fidelity.

Figure 1. Expansion Sequencing.