How do proteins evolve to bind and regulate RNA?

Proteins gain and lose functions over the course of evolution. Enzymes can change their substrate or lose their activity, and binding proteins can change their preferred binding partners. We found a very nice example in fungal Ssd1, an RNA-binding protein that regulates translation and that is a catalytically dead descendant of an RNA-degrading enzyme. Combining biochemical and structural information with large-scale bioinformatics analysis allowed us to tell when in evolutionary history the ancestors of Ssd1 lost one function and gained another.

 How many other examples are there of proteins that gain and lose RNA-binding function? What could they tell us about the fundamental principles of RNA binding and protein evolution? New proteomics methods show that hundreds of different proteins bind RNA to regulate gene expression, and it will be very interesting to apply these methods across many organisms to track changes.

 This PhD project will combine experimental and computational methods to understand evolution of RNA-binding proteins using fungi as a model system. We aim to collect datasets of the RNA-bound proteome in different fungi and aim to discover cases where RNA binding has been lost or gained in the protein family. We will use evolutionary and structural bioinformatics to make detailed hypotheses about changes in binding, that we will test using assays such as CRAC (sequencing for RNA-protein binding) and ancestral protein reconstruction to measure conservation of function in model yeasts.

 This project would suit a student interested in evolution at the molecular level, and who is excited to learn a range of computational and experimental skills. A motivated student with a computational background will be taught lab skills, or the other way round. We are committed to the well-being and career development of lab members and also we advocate for open science. Please get in touch with any questions.

http://ewallace.github.io

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