Background:
GCN2 is a protein kinase, which is relevant not only for cancer but also for neurodegenerative diseases such as Alzheimers. GCN2 has long been known as a translation regulator in stress responses. Only one substrate is known and the literature attributes all the functions of GCN2 to the phosphorylation of this substrate. However, several findings hint at other important and yet unknown functions. Our working hypothesis is that the GCN2 protein kinase is a major player supporting cancer growth and therefore it is an attractive target for therapy. In the course of several previous master projects we have
- identified correlations between GCN2 and other genes in transcriptome data from cervical cancer patients. We found correlations that suggested specific novel functions.
- confirmed some of these correlations by qPCR using cell-lines with different levels of GCN2. Furthermore, initial phenotypic analyses suggested that GCN2 indeed has novel functions highly relevant for cancer.
Goal :
In the current project we wish to study these novel cancer-relevant functions of GCN2 further. A major focus is mitosis, building on our recent finding that GCN2 is essential for mitosis in cancer cells but not in “normal” (not transformed) cells. Our hypothesis is that the differential impact of GCN2 inhibition on cancer versus normal cells gives the unique possibility to selectively target cancer cells.
Our aims are
- to understand the basis for this difference and
- to develop it into a framework to exploit the finding in cancer therapy
Approaches:
We utilize a wide variety of cell- and molecular biology techniques, including molecular genetics, live-cell microscopy, flow cytometry, growth and viability assay.
The group:
We belong to the Department of Radiation Biology at the Institute for Cancer Research at the Radiumhospital. My group currently consists of a postdoc, and an experienced technician and we are looking for master students. We are looking to recruit one or two students.
Contact person:
- Beata Grallert, Department of Radiation Biology, Institute for Cancer Research (Radiumhospitalet) beata.grallert@rr-research.no