The role of riboregulators and RNA-binding proteins in regulating adaptive responses in microorganisms.
My group is studying the role of riboregulators and RNA binding proteins in regulation of gene expression during adaptive responses. Many microorganisms, in particular human pathogens, have evolved clever mechanisms to be able to very rapidly adapt to stress caused by environmental changes, such as changes in host temperature and nutrient availability. This enables them to efficiently maintain cellular homeostasis even in hostile environments. Our goal is to gain mechanistic insights into regulatory strategies used by these organisms to adapt to stress.
Our research focusses on riboregulators and RNA-binding proteins that play a key role in stress adaptation. In collaboration with Jay Tree (University of Sydney), David Gally (Roslin Institute) and Ross Fitzgerald (Roslin Institute) we are currently working on a number of bacterial pathogens to unravel the role of these factors in the post-transcriptional regulation of gene expression (for example, see Tree et al 2014, van Nues et al 2017 and Iosub et al 2019).
This work is sponsored by generous contributions from:
The role of RNA-binding proteins in ribosome assembly
Until recently we also studied the mechanisms of ribosome synthesis and its relationship with cancer and cell division. Ribosomes are large RNA-protein complexes that translate mRNA into protein in the cytoplasm of eukaryotic cells. Ribosomes are largely synthesized in a subnuclear compartment called the nucleolus. In eukaryotes, three of the four ribosomal RNAs (rRNAs) are transcribed as a single precursor (35S pre-rRNA in yeast) that is processed at several well-defined sites to generate the mature 18S, 5.8S and 25S rRNA. Pre-rRNA processing takes place in large complexes called pre-ribosomes, which are the precursors to the ribosomes.
A growing mammalian cell produces about 7500 ribosomes per minute, requiring around 600,000 ribosomal proteins and involve over 200 trans-acting factors, necessary for the synthesis of ribosomal RNA (rRNA) and ribosomal subunit assembly. In interphase cells the number and size of nucleoli and the rate of ribosome synthesis directly correlate with cell proliferation rates, and aberrant nucleolar morphology is a hallmark of cancer cells. However, little is known about how the process of ribosome assembly is coupled to cell proliferation and a detailed understanding of ribosome biogenesis is required to comprehend these links.
The goal of our research is to gain molecular insights into the dynamics of ribosome assembly in yeast using state-of-the-art biochemical and high-throughput approaches (see Hector et al 2014, Selega et al 2017, Burlacu et al 2017, Lackmann et al 2018)
This work was sponsored by generous contributions from: