EASTBIO: How do RNA-binding proteins regulate fungal cell walls and environmental adaptation?

Supervisors:

Professor Alistair Brown (University of Aberdeen) https://www.abdn.ac.uk/ims/profiles/al.brown

Dr Edward Wallace (University of Edinburgh) https://ewallace.github.io/

What scientific question will you investigate?

Fungi live in diverse environments and display remarkable morphological diversity, switching between yeast and filamentous lifestyles, and changing the composition of the cell wall that mediates interactions with their environment (Hopke 2018). The yeast, Candida albicans, is adept at switching from a harmless component of our microbiota into an aggressive cause of infection, rapidly tuning its gene expression and remodeling its cell wall to adapt to different niches in our bodies. The aim of this project is to understand how RNA-binding proteins tune gene expression to regulate the C. albicans cell wall and environmental adaptation.

The project will focus on the regulatory factor Ssd1, an RNA-binding protein conserved across fungi. In C. albicans, Ssd1 regulates cell shape through the transcription factor Nrg1 (Lee 2015), and is required for virulence. In the model yeast Saccharomyces cerevisiae, Ssd1 is required for stress tolerance and protein disaggregation, and regulates translation of mRNAs coding for cell-wall remodeling proteins (Jansen 2009).

The objective of this project is to find out which RNAs are regulated by Ssd1 in C. albicans, and how that affects the cell wall. You will use cutting-edge sequencing assays to measure which RNAs bind Ssd1. You will use bioinformatics and statistical software to analyze this data, working alongside colleagues in the Wallace lab applying similar approaches to S. cerevisiae. You will measure the effects of Ssd1 mutations on C. albicans cell wall composition and stress resistance. Ideally, these objectives will come together in a detailed understanding of how regulation of specific mRNAs leads to specific cell wall remodeling events, building substantial understanding of how fungi respond to their environment.

What training will you receive?

You will be broadly trained in 21st-century interdisciplinary biology from the molecular level up to the fungal cell, including dealing thoughtfully with large datasets. In Aberdeen, you will learn how to work with C. albicans and genetically engineer protein mutations and tags. You will learn to measure cell wall composition, including antibody-based quantification by flow cytometry and microscopy. In Edinburgh, you will learn how to work with RNA and prepare next-generation sequencing libraries. You will learn best practices in bioinformatics, including statistical analysis, and receive formal training and apprenticeship in the large datasets that are essential to modern biology.

Both the Brown and Wallace labs will support your career development including presentation and writing skills.

What could you do afterwards?

The completion of this project will build the skills to tackle a range of problems in biology and beyond. There is huge demand for people who can combine experimental and computational insight to make sense of big data.

You will be well-placed to capitalize on the growing interest in fungi as important model organisms, cell factories, microbiome occupants, and pathogens; these are strategic priorities for UK funding councils. This project uses exciting high-throughput techniques and you would be particularly suited to apply these to other questions in fungi or other organisms.