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A current major challenge in biology is to understand how gene expression is regulated with surgical precision in a tissue-dependent, spatial and temporal dimension. Historically, genome-wide studies of gene expression have typically measured mRNA abundance rather than protein synthesis, in large part because such data are much easier to obtain. However, the correlation between mRNA levels and protein abundance is as low as r=0.35-0.40, suggesting that transcriptional regulation alone is not sufficient to unveil the complex orchestration of gene expression. In the last few decades, the scientific community has started to acknowledge the relevance of the post-transcriptional regulatory layer, which has led to fields of study such as miRNA regulation, alternative polyadenylation and RNA epitranscriptomics, amongst others. However, we are still far from understanding how gene expression is finely tuned and regulated across tissues and conditions, suggesting that we are missing variables in the equation. To fill this gap of knowledge in the field of post-transcriptional regulation, we aim to explore ribosome specialization as a novel layer to tune the proteome of metazoan cells.

For many decades we have envisioned the ribosome as an invariant static entity. However, human ribosomal protein mutations can affect a specific cell type, and lead to a tissue-specific human disease, called ribosomopathies. How can a defect in a macromolecule that is as ubiquitous and essential as the ribosome cause disease that is selective for a given tissue? Tissue-specific ribosomopathies can indeed be explained by the existence of tissue-specific regulation of ribosome composition. Here we aim to characterize and decipher the biological roles of human tissue-specific ribosomes, and build the foundations of a novel uncharacterized regulatory layer capable of tuning gene expression levels.

Thus, here we specifically aim to:

1) Systematically characterise specialised ribosomes both in human and mice, and determine their composition across tissues

2) Determine which specific stressors/stimuli lead to changes in ribosome composition

3) Determine the biological role of specialized ribosomes

4) Determine the evolutionary conservation of specific ribosome compositions across species

Interested in working in this amazing new field of research as PhD/Honours/Masters student?

Contact me at : e.novoa[at]garvan.org.au, including your CV and a brief description/statement of interest.

Eva Maria Novoa 
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