New genetic, imaging and microfluidics technologies for single cell genomics (360G-Wellcome-108438_C_15_Z)

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.