Cancer Research UK Career Development Fellow
Phone: 020 7848 6567
For publications etc., see lab members below.
- Rita Sousa-Nunes, Cancer Research UK Career Development Fellow
- Orangel Gutierrez , Visiting student
- Ana Mateus, Research Associate
- Rachel Shaw, Research Technician
Neural Proliferation and Tumourigenesis
We are interested in neural proliferation and how its disruption can lead to immortal and invasive tumours. We use a variety of model organisms, starting from fundamental insights obtained from studying the little fruitfly Drosophila melanogaster. We then investigate conservation in vertebrates of the molecular and cellular processes found.
Central nervous system (CNS) tumours are the most prevalent class of solid tumours developed by children. Therapies currently employed to treat them can have severe consequences on a child’s cognitive development so safer methods are greatly needed. A subset of CNS tumours is generated by disruption of neural progenitor asymmetric divisions, in mammals as well as in flies. Indeed, the more we learn about vertebrate neural stem cell development – and the consequences of its disruption – the more similar (albeit much more complex) it appears in its principles to what has been found in the fruitfly.
Drosophila CNS stem cells (called neuroblasts) divide asymmetrically, generating another identical stem cell (self-renewal) and a proliferation-restricted transit amplifying daughter that divides a limited number of times to produce differentiated progeny.
Disruptions to larval neuroblast divisions that generate two neuroblast-like daughter cells can lead to immortal and metastatic tumours.
Drosophila is a relatively simple yet very powerful metazoan model organism, where sophisticated genetic tools allow for a comparatively fast yet rigorous assessment of gene function in the context of a whole tissue or animal. Approximately one third of human genes encode proteins of uncharacterised function so there remains need for gene function discovery, in addition to ascribing physiologically significant roles to known genes. The power of Drosophila genetics has already been applied to the discovery of mutations leading to tumour formation and metastasis, many of which lie in genes conserved in humans. The compact genome of Drosophila (~14,000 protein-coding genes) relative to that of mammals frequently contains a single orthologue per few mammalian homologues but, nonetheless, includes over 70% of counterparts for human disease genes. Furthermore, overexpression and mutant or knock-down flies exist for the vast majority of its genes, which, along with its genetic tractability, make this an extremely attractive organism in which to screen in vivo for the genetic basis of tumour formation and progression.
Therefore, in the concerted efforts towards combating cancer, Drosophila has an important role to play, both for the intellectual insights it can offer and for the reduction of usage of animals with which there are ethical considerations. We believe that the employment of a range of models will speed up our understanding of the regulation of neural proliferation and cancer.