The level of ribosomal RNA synthesis by RNA polymerase-I (Pol-I) is rate-limiting to ribosome biogenesis and therefore has a major influence on the cellular capacity for protein production, making Pol-I transcription fundamental to life. The production of ribosomal RNA is tightly linked to cell growth and proliferation in eukaryotes. Deregulated rRNA production can have a dramatic effect on the fate of cells: insufficient rRNA production is lethal, whilst excessive rRNA production can lead to defects in cell proliferation, cell death, or uncontrolled growth of cell size. These defects might contribute to oncogenic transformation of cell or developmental defects. Further research into the basic mechanisms of Pol-I transcription and its regulation will have a significant impact on our understanding of the interplay between fundamental cellular processes such as ribosome biogenesis and cell proliferation, and have the potential to drive the development of novel drugs targeting diseases associated with hyperproliferation and abnormal cell size including cancer and heart disease. Because elevated levels of rRNA synthesis are required to support the unrestrained proliferation of cancer cells, rRNA biosynthesis represents a valid target for anticancer therapy as well as providing opportunities for the diagnosis of cancer. Furthermore, drugs promoting rRNA synthesis might be useful for stimulation of cell growth and proliferation in cell-replacement therapy strategies.
My main research interest are: the biochemistry of Pol I transcription, molecular and cellular mechanisms involved in the regulation of rRNA synthesis, signalling pathways and other regulatory mechanisms targeting rRNA synthesis and ribosome biogenesis and discovery of novel drug targets related to ribosome biogenesis.
Enquiries from post graduates/post docs who have independent funding or fellowships, and who wish to join our studies of ribosome biogenesis, are welcome
Research in my lab is supported by: