Role of RNA-binding proteins in cancer
PhD Research
Funding:
The full studentship (fees and stipend) is available to UK or EU students who have been resident in the UK for at least three years. Other EU participants may receive a fees only award.
Applicants capable of self-funding (UK, EU and international) are also welcome to apply.
Project details:
Primary supervisor: Dr Sonia Lopez de Quinto
Second Supervisor: Dr Helen White-Cooper
Many cellular functions rely on the generation and maintenance of cell asymmetries, also known as cell polarity. This is achieved by the asymmetric accumulation of key proteins in specific cellular domains where they exert their function. Importantly, loss of cell polarity is a critical event during cell malignancy transformation and thus, cancer progression.
mRNA localization coupled to local and temporal translation has emerged as a powerful mechanism for the generation and maintenance of cell polarity. This RNA-based mode of gene regulation plays a role in the development of human diseases such as cancer, genetic neurological disorders and viral infections. Of particular relevance to cancer progression is the regulation of the local translation of b-actin mRNA at the leading edge of migrating cells (Shestakova et al. 1999, Cancer Research 59:1202-05) and the discovery of a new RNA localization pathway involving the tumour-suppressor protein APC (Mili et al. 2008, Nature 453:115-9).
We have characterized the role of two hnRNP proteins in the temporal and spatial regulation of RNAs controlling the development of the Drosophila embryo's body axes (http://www.cardiff.ac.uk/biosi/contactsandpeople/stafflist/i-l/lopez-de-quinto-sonia-dr-overview_new.html). Interestingly, these highly conserved RNA-binding proteins have emerged as key players in cancer (Carpenter 2006, Biochim Biophys Acta. 1765:85-100). The PhD project will use Drosophila as a model system to investigate how the interaction of hnRNPs with mRNAs in the cytoplasm regulates cell migration, an essential property of metastatic cells. Elucidation of these mechanisms has the potential to identify new intervention strategies of potential high impact. The study will employ a wide range of techniques (genetics, molecular biology, biochemistry, cell biology, confocal microscopy, bioinformatics) to address the physiological relevance of these processes in the context of a living organism.