Second ERC Advanced Grant for Alexander van Oudenaarden

Alexander van Oudenaarden received his second ERC Advanced Grant. With this grant, Van Oudenaarden wants to study the genetic activity of individual cells while pinpointing their specific position at a specific time. 

From populations of unicellular organisms to complex tissues, cell-to-cell variability in phenotypic traits seems to be universal. To study this heterogeneity and its biological consequences, researchers have used advanced microscopy-based approaches that provide exquisite spatial and temporal resolution, but these methods are typically limited to measuring a few properties in parallel. On the other hand, next generation sequencing technologies allow for massively parallel genome-wide approaches but have, until recently, relied on studying population averages obtained from pooling thousands to millions of cells, precluding genome-wide analysis of cell-to-cell variability.

Very excitingly, in the last few years there has been a revolution in single-cell sequencing technologies allowing genome-wide quantification of mRNA and genomic DNA in thousands of individual cells leading to the convergence of genomics and single-cell biology. However, during this convergence the spatial and temporal information, easily accessed by microscopy-based approaches, is often lost in a single-cell sequencing experiment.

Three lines of research

The overarching goal of Van Oudenaardens proposal is to develop single-cell sequencing technology that retains important aspects of the spatial- temporal information. In particular he will focus on integrating single-cell transcriptome and epigenome measurements with the physical cell-to-cell interaction network (spatial information) and lineage information (temporal information). These tools will be utilized to (i) explore the division symmetry of intestinal stem cells in vivo; (ii) to reconstruct the cell lineage history during zebrafish regeneration; and (iii) to determine lineage relations and the physical cell-to-cell interaction network of progenitor cells in the murine bone marrow.

Taken together this technology will provide a platform for integrating spatial and temporal information with the transcriptome and epigenome of individual cells providing an unprecedented view of a cell’s expression state, physical neighborhood, and family history, all simultaneously quantified in vivo.

Read more about the single cell research at the Van Oudenaarden lab here.