Peptide barcode enabled lineage tracing with mass spectrometry based single-cell proteomics

Our understanding of how cellular programs orchestrate complex molecular machinery to shape multicellular organisms and the intricate communal interactions among bacteria and fungi is one of the fundamental questions in biology. The advent of lineage tracing technologies has provided incredible insight into this pivotal area. Currently such tracking technology is based on nucleotide sequencing technology that measures transcripts, but which is blind to proteins - the functional subunits of the cell. To this end, we aim to develop a tool that combines cell progeny tracking with mass spectrometry (MS) based-single-cell proteomics. With genetic engineering we will establish short unique peptide sequence panels that can be mixed and matched to generate thousands of unique barcodes to label individual cells. These barcodes remain stably propagated through division and can be quantified by MS, thereby obtaining both the lineage information and  the cellular proteome.