This proposal involves the molecular characterisation of DLRIG-1, the fruitfly homolog of a novel tumour suppressor gene. With its unparalleled genetic tools the fruitfly, D. melanogaster, provides a powerful experimental system to unravel the function of t his novel cancer gene in vivo.
Indeed, a large number of molecular pathways implicated in human tumour biology, have conserved homologs in the fruitfly. DLRIG-1 encodes a novel protein with leucine rich repeats and immunoglobulin domains. During my training years at the Howard Hughes Medical Institute (USA) I generated preliminary data and experimental reagents, which I will now apply to this project.
I will address the following specific questions: first, what are the phenotypic effects of mutations of DLRI G-1 in the fly? Secondly, how does DLRIG-1 interact with EGFR (epithelial growth factor receptor) signalling in the fly and what is the molecular mechanism? I anticipate that the results of this project will provide mechanistic insight required for the design of translational research projects aimed at improving treatments of brain tumours (e.g. glioma) that are caused by disregulated EGFR signalling.
With its focus on Drosophila neurobiology and morphology the newly established Laboratory of Developmental Genetics at V.I.B. provides a well-suited environment for my research. My return to Leuven as a fruitfly geneticist will add momentum to its emerging Drosophila research community. Through my medical background I will also be well positioned to foster collaborations between the Drosophila research community and the many translational biomedical researchers at Leuven and elsewhere in Europe.
In addition, as scientist at V.I.B., I will gain additional expertise in nervous system morphology and strengthen my leadership skills. Altogether, the DLRIG-1 project in Leuven will serve as a stepping-stone for my further career as physician-scientist in Europe.
Call for proposal
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