Research group Mihaela Zavolan
Gene expression regulatory programs
Identification of gene expression regulatory programs could suggest new approaches to manipulate cell fate.
Although all cells in our bodies carry the same genetic material, they express different subsets of genes and thereby have widely different shapes, sizes and functions. Gene expression is regulated at many levels, by many different regulators. We are interested in uncovering ‘programs’ of gene expression that are orchestrated by individual (or groups of related) regulators acting on large sets of genes to implement behaviors such as self-renewal and differentiation.
Gene expression programs and regulators
Gene expression is a complex process that comprises changes in the chromatin state, transcription initiation/termination, pre-mRNA formation, splicing, export to the cytoplasm, translation, and mRNA and protein decay, among others. All of these steps are subject to regulation. Some regulators act on many target genes at a time, and could be seen as implementing gene expression ‘programs’. Transcription factors are a prime example, but systematic changes in splicing patterns due to tissue-specific splicing regulators, systematic changes in the length of the 3’ untranslated regions of mRNAs and coherent regulation of multiple members of biochemical pathways by microRNAs have also been observed.
High-throughput data combined with computational models
Powerful technologies are available today that allow us to probe expression of essentially all genes at the same time. We analyze such high-throughput data obtained from various types of cells with computational models, to understand how regulators exert their functions within gene regulatory networks.
Towards new strategies for manipulating cell fateMany of the regulators that we study are linked to cell fate. Some splicing factors regulate developmental transitions, while other behave as oncogenes. Pre-mRNA 3’ end processing factors regulate 3’ UTR length, and short 3’UTRs are expressed in proliferating cells, including cancer cells. MiRNAs have been reported to repress gene expression and reduce its stochastic variation between cells. A detailed understanding how these factors act and what leads to their aberrant expression could provide clues for regulating cell fate.