Causes and effects of intrinsic gene synchronicity in single cells (InSync)

There is a huge interest in identifying genes that are synchronized in expression, since these are often functionally related and function in the same pathways.

Such charting mostly leverages on profiling across hundreds of distinct tissues - therefore it would be enabling to instead detect synchronized genes across single cells.

However, such measurements are confounded by extrinsic noise, including the cell cycle and differentiation.My group has developed a stringent framework to remove these confounders - allowing us to detect intrinsic gene synchronicity in mammalian single cells.

We can use this synchronicity to measure strength and prevalence of gene regulation in our cells of interest, and we find that synchronized genes are indeed functionally related and give rise to proteins that are part of the same complexes.We propose to map gene synchronicity in the K562 ENCODE cell line, for which vast amounts of multi-omics data are available.

We will leverage on these data to understand in fine resolution the regulatory causes of the synchronicity. We will further apply CRISPR to specifically disrupt synchronicity, and we will measure molecular and cellular effects.

Lastly, we will study patterns of gene synchronicity across various types of cancer, looking for pan-cancer signatures.This project will elucidate causes and effects of intrinsic synchronicity: a novel aspect of gene regulation that is conserved from yeast to mammals, with possible implications for human health.