Dr Faraz Mardakheh, Group Leader in the Centre for Cancer Cell & Molecular Biology at Barts Cancer Institute, Queen Mary University of London, has recently received a project grant from the Medical Research Council, part of UK Research and Innovation.
The main research focus of Dr Mardakheh’s laboratory is on understanding how protein production is dysregulated in cancer cells, and how this dysregulation contributes to various stages of cancer progression. A key interest of Dr Mardakheh’s laboratory is understanding how RNA molecules, which act as intermediates between genes and proteins, are distributed within cells, and how this distribution impacts the regulation of protein production. The new project grant of approximately £465,000 over 3 years will support research that will aim to systematically decipher how this process (known as RNA localisation) becomes dysregulated during cancer progression.
We spoke with Dr Mardakheh to find out more about the plans for the project.
RNA is an important biological molecule that decodes the genetic information stored in DNA into instructions for protein production in cells. In cancer, RNA-related processes can become dysregulated, altering protein production and contributing to cancer development and progression.
Under normal circumstances, RNA molecules travel to defined destinations inside cells to control gene expression in a process known as RNA localisation. Our lab has recently discovered that RNA localisation can be disrupted in cancer - we found that as human cells evolve from normal to cancerous, there is progressive mis-localisation of key groups of RNA molecules to different compartments within the cell. This project aims to systematically investigate how these mis-localisation events happen, as well as revealing their functional contribution towards the development and progression of cancer.
It is now clear that a significant degree of gene expression dysregulation that occurs in cancer happens after RNA has been generated from DNA (i.e. at the post-transcriptional level). We hope that our research will uncover previously unknown processes that contribute to RNA mis-localisation in cancer cells. By understanding these processes better, we hope that our findings will pave the way for the development of strategies to detect post-transcriptional dysregulations in tumours via monitoring RNA localisation, and to therapeutically target these cancerous changes by interfering with RNA mis-localisation mechanisms.
We utilise various state-of-art omics methodologies, along with cutting edge RNA imaging techniques in order to map, validate, and monitor RNA localisation changes during the progression of breast epithelial cells from normal to a highly malignant state. We will employ a novel mass spectrometry-based technique to study RNA-protein interactions at the endogenous level, in order to determine the molecular causes and consequences of RNA mis-localisations. We will also use in vitro and in vivo loss-of-function assays to characterise the impact of these discovered mis-localisation pathways on disease progression.