scroll
UP

Careers & Students

Dissecting the role of a novel molecular pathway in haematopoietic stem cells

Dissecting the role of a novel molecular pathway in haematopoietic stem cells

PhD project

We have found that Drosha, one of the RNase III enzymes necessary for microRNA biogenesis, also functions to regulate the stability of certain protein-coding mRNAs. This occurs via recognition and cleavage of secondary stem-loop structures within these mRNAs. We have found that this activity is largely restricted to and critical for the function of stem cells. In particular, we showed that Drosha-mediated mRNA cleavage is required in haematopoietic stem cells for the differentiation of myeloid lineages (dendritic cells, monocytes, granulocytes, etc). Furthermore, we believe that defects in this pathway contribute to certain diseases of the haematopoietic system, particularly myelodysplastic syndrome. The goal of this project is to understand how this mRNA cleavage mechanism is regulated in stem cells and its potential involvement in haematopoietic diseases. This will involve the analysis of various genetically modified mouse models, and will employ a range of genomic, molecular and cellular techniques.

References:
Johanson (2015), Nat Immunol, 16:1134-41.
Knuckles (2012), Nat Neurosci, 15:962-9.
Karginov (2010), Mol Cell, 38:781-8.

Supervised by:

  • Dr Mark Chong
  • Disease Focus:

  • Cancer
  • Type 1 diabetes
  • Research Unit:

  • Genomics and immunology