Fungi control their growth to thrive in varied environments. Fungal pathogens are a major worldwide health burden, killing more people each year than malaria or tuberculosis. We hypothesize that conserved RNA binding proteins (RBPs) have a major role in controlling fungal growth in response to the environment, by allowing precise temporal and spatial control of protein production within fungal cells. For example, the Ssd1 protein binds the messenger RNAs encoding some protein components of the fungal cell wall, probably to control their translation near the growing tip of the cell. Also yeast (unicellular fungi) are easy to engineer and work with, making them excellent model systems to understand protein production.
This project is an interdisciplinary mixture of lab-based molecular and computational biology studies, that will use cutting-edge quantitative methods to study how RBPs regulate protein production from messenger RNA. Using rapid cross-linking and cDNA analysis (CRAC) the student will generate RNAseq libraries that will give global, high-resolution datasets (in time and sequence space) of changing RNA-protein interactions over environmental responses. We will use bioinformatic analyses to identify motifs within RNA that these RBPs recognize, and test these predictions by genetic engineering and reporter or sub-cellular localisation assays. There will be opportunities to use available fungal genome sequences to study the evolution of both proteins and their regulatory targets. There will be further opportunities to develop structural bioinformatics and analysis skills through interactions with the Cook Lab, to develop molecular-level hypotheses of protein function that can be tested in vitro. Overall, the work will give mechanistic insights into how RNA-binding proteins control fungal growth in response to the environment, in budding yeast and pathogenic fungal models.
The successful candidate will be excited to combine experimental (yeast, RNA, proteins) with computational (bioinformatics, statistics, structural modeling, phylogenetic) methods. You will have demonstrated basic skills in either wet and dry work and, during the PhD, will be trained to a high level in both. You will join a thriving research collaboration, in a vibrant research environment focused on fundamental cell biology and bioinformatics. Both groups will support your career development including laboratory, programming, presentation and writing skills. You will be encouraged to build a network of scientific colleagues, including presenting your work at conferences.
This project will be supervised by Edward Wallace (https://ewallace.github.io/) and Atlanta Cook (http://cook.bio.ed.ac.uk/). Interested candidates should email enquiries to us, describing their specific interest in this project in specific terms.
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