Group Leader: Dr Ivana Bjedov, Senior Research Fellow
We are interested in the regulation of growth and metabolism during cancer. Cancer is characterised by uncontrolled cell division - for cancer cells to be successful in proliferation, a major change is the up-regulation of growth pathways and the reorganisation of metabolism to produce the energy and building blocks necessary for cell division. We aim to identify novel alterations in cancer cells that are crucial for their proliferation and that distinguish them from normal cells, thereby uncovering potentially less harmful anti-cancer targets. In our research, we use the fruit fly Drosophila melanogaster, which has already greatly contributed to our understanding of cancer and the discovery of several cancer-related growth pathways. Many features of human cancer can be replicated in Drosophila. This model system has many advantages such as its short generation time, low gene redundancy, and powerful genetic techniques that allow the rapid testing of various hypotheses.
We are also investigating novel modulators of cancer, specifically autophagy. The autophagy process has recently been associated with cancer, as haploinsufficiency of the autophagy gene Becn1 is tumorigenic. Autophagy is a cellular “self-eating” process, which under conditions of low nutrients or growth factors captures and degrades a portion of the cytoplasm, thereby supplying the cell with amino acids, fatty acids and energy. Protein aggregates and also entire organelles such as mitochondria can be degraded by autophagy. The main regulator of autophagy is the nutrient-sensing target-of-rapamycin (TOR) pathway (Figure 1). The relationship between autophagy and cancer is complex: autophagy inhibition promotes cancer initiation through the generation of genomic instability and inflammation. Whereas in contrast, autophagy activation is often required to sustain the growth of advanced solid tumours in a nutrient-deprived hypoxic environment. Therefore we aim to uncover how best to modulate autophagy to suppress tumours and to avoid resistance in anti-cancer therapy.
Castillo-Quan JI, Kinghorn KJ, Bjedov I. (2015).Genetics and pharmacology of longevity: the road to therapeutics for healthy aging. Adv Genet. 2015 July 29;90:1-101.
Bjedov I, Partridge L (2011) A longer and healthier life with TOR down-regulation: genetics and drugs. Biochem. Soc. Trans. 2011 Apr 1;39(2):460-5.
Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010 Jan;11(1):35-46.