Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

New genetic, imaging and microfluidics technologies for single cell genomics

In plain English

AI plain-English summary

Every cell in a tissue carries a unique history and location, but current single-cell genomics discards both. This project builds three technologies to recover that lost information: microfluidic devices that process tens of thousands to millions of cells per day instead of hundreds, genetic recording tools that write each cell's lineage into its own genome, and fluorescent tags that mark where in a tissue a cell came from. The problem is that existing single-cell methods are like reading a book after shredding it and mixing the pages. Researchers can sequence individual cells, but they cannot tell which cells were neighbours, which are descendants of the same parent, or how position influenced gene activity. Without that context, understanding how cells diversify during development or disease remains incomplete. If successful, these tools will let biologists map cell family trees directly onto tissue architecture at unprecedented scale. This is fundamental science—it will not immediately change a medical treatment or a manufacturing process. But similar advances in single-cell technology have already reshaped cancer biology and immunology. A deeper understanding of how cells coordinate their identities in space and time could eventually inform regenerative medicine, tumour classification, or tissue engineering.

View original technical description
Two major limitations of single cell genomics is (i) the loss of information about the original location within the sample of the sequenced cell and (ii) low throughput at high cost with only hundreds of cells analysed per day. Miniaturising single cell analysis to pico-litre volumes will critically facilitate higher throughput (10^4 - 10^6cells) at lower costs and sidesteps restrictions in handling. Combined with genetic technologies to record lineage history and spatially localise cells this w ill allow questions to be address at single cell resolution that are essential to understand cell diversification following tissue-contextual interactions and the impact it has on gene transcription. 1) We will develop microfluidics based devices to increase sequencing throughput by increasing the number of cells processed at a low cost, and at the same time enabling the complex handling and manipulation of small cell numbers with minimal loss. 2) We will develop genetic technology to: i) record within the genome the lineage history of each cell, for readout at any stage of interest and ii) to provide a unique fluorescent signature to cells to enable us to provide spatial and temporal context to their transcriptional profiles.

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Researchers

Chris Ponting (EPMC Awardee)Florian Hollfelder (EPMC Awardee)John Marioni (EPMC Awardee)Shankar Srinivas (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Microfluidic devices for 3D super-resolution imaging of single molecules in live cells
Development of single-cell sequencing technology for microbial populations
Development of a microfluidic device to study single cells in controllable microenvironments
Enhancing multi-omic single cell sequencing to resolve fundamental biological mechanisms in humans and non-human organisms
Establishing a single cell genomics facility

Original classification

Technology Development Grant

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