Science
We study RNA modifications, RNA splicing, long non-coding RNAs and the regulation of gene expression during germline development.
During development, cells constantly face a decision between dividing and differentiating, and the regulation of gene expression is central to that decision. RNA sits at the heart of many of those regulatory processes. We try to understand how different RNA-mediated mechanisms control gene expression as germ cells proliferate and differentiate.
Three questions
What do the marks on snRNA do?
More than 150 chemical modifications exist on RNA and for most of them nobody knows the biological job. We use genetics, mass spectrometry and nanopore sequencing to find out what the enzymes that write them are for.
How do they steer splicing?
Splicing cuts out introns, and many animals also swap the 5′ end of an mRNA by SL trans-splicing. We ask how modified RNAs and splicing factors decide between those routes in the developing germline.
Who pays for the methyl?
Every methyltransferase spends SAM, and regenerating SAM needs vitamin B12 that the animal gets from its bacterial diet. We change that supply and watch what happens to methylation and gene expression.
RNA modifications
More than 150 distinct chemical modifications are found on RNA. They control the processing, stability, expression and function of diverse RNA types. For most of them we still do not know the biological role in a multicellular organism. We use a combination of genetic and biochemical tools to study what RNA-modifying enzymes and their marks do during animal development.
RNA splicing
Splicing is generally known for removing intronic sequences and ligating exons, which preserves the accurate expression of coding and non-coding genes. In addition, many organisms change the 5′ end of their mRNAs using SL trans-splicing. We study how RNA modifications and splicing factors regulate both cis- and trans-splicing during germline development.
Metabolic regulation of gene expression
Dietary metabolites are required for a large number of cellular processes. Among these, vitamin B12 is essential for the cellular regeneration of S-adenosyl methionine (SAM), and every methyltransferase enzyme spends SAM during a methylation reaction. We are studying how changing SAM levels in an organism affects gene expression and cellular methylation.
How we work
- Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to quantify RNA modifications
- Oxford Nanopore direct RNA sequencing to detect modified RNAs
- Genetics and CRISPR/Cas9 genome editing to generate mutants and transgenic lines
- In vivo and in vitro assays for RNA splicing, modification and gene expression
- Confocal microscopy for co-localisation and gene expression
We use the nematode Caenorhabditis elegans as a discovery organism. Its germline development is an ideal system for studying RNA modifications and modifying enzymes, RNA splicing and gene expression through cell proliferation and differentiation. Alongside C. elegans we work with bacteria, yeast and human cells.
We work in
- NematodesC. elegans
- BacteriaE. coli
- YeastS. cerevisiae
- Human cellsin culture