What is the role of RNA degradation in shaping the brain?
The development of the brain requires a complex series of cell fate decisions that are mediated by changes in gene expression. The first step in gene expression is production of the mRNA from the genomic template via transcriptional regulation. Important work from other groups is focused on defining the signals that regulate the transcription of genes with key developmental importance. But what happens to these mRNAs after they leave the nucleus, and how are the activities of their gene products confined to the correct cell types? We know from the literature that neural stem cells must perform a delicate balancing act. Their gene expression program is carefully calibrated to allow rapid asymmetric cell division to yield a differentiating daughter cell at each division, while they must themselves maintain their non-differentiated state. I am interested in assessing how post-transcriptional processes contribute to the precise timing and outcome of these developmental transitions.
We are looking at the kinetics of RNA production and decay in living brains using both biochemical and imaging approaches.
Genome-wide quantification of transcription and decay rates in the fly brain
We use 4-thiouridine (4sU), a thiolated analog of uridine to specifically tag newly synthesized RNAs in living fly tissue, such as brains and neuromuscular junction preparations.
A metabolic labeling experiment for measuring mRNA transcription and decay rates
A uridine analog, 4-thiouridine, is added to brains at the beginning of the experiment. The fraction of labeled mRNA will increase as a function of time and can be used to estimate transcription and decay rates through mathematical modeling.
Visualizing transcription and mature RNA and in developing brains
We use single-molecule fluorescent in situ hybrization (smFISH) to visualize and count individual RNA molecules in the fly brain.
I joined the Davis lab as a postdoctoral researcher in 2015. I am investigating the role of post-transcriptional regulation in brain development and synaptic plasticity.
Education:
2008-2015: Ph.D. (Biology)
Massachusetts Institute of Technology (MIT), Cambridge, USA
2004-2008: B.S. (Biochemistry & Cell Biology)
Rice University, Houston, USA
Contact:
email: mary.thompson@bioch.ox.ac.uk