Gene regulation in the developing retina and the childhood eye cancer retinoblastoma

Summary Retinoblastoma is the most common eye cancer of infancy and childhood; these tumours are considered to be developmental in origin. The seven cell types of the retina all derive from a pool of retinal progenitor cells (RPC). The distalless (DLX) family of evolutionarily-conserved homeobox genes encode transcription factors expressed in the developing and mature retina as well as the majority of retinoblastoma tumours examined to date. The DLX transcription factors are necessary for retinal ganglion cell (RGC) development, in part due to direct regulation of other transcription factors that are either activated or repressed during eye development. The student will undertake RNAseq and ChIPseq studies in the developing mouse retina to identify DLX2 gene regulatory networks, validate in transgenic mouse models available in the laboratory and assess expression of these DLX2 targets in retinoblastoma and/or retinal organoids. The student will also contribute to the generation of a conditional, retina-specific knockout of Dlx2 or both Dlx1/Dlx2 in the developing and/or postnatal mouse. The student will learn key methods in molecular, cell and developmental biology, including primary cell culture, 3D organoids, and advanced microscopy skills. The student should preferably have an undergraduate or advanced background in cell, developmental and/or molecular biology.

Project Details

Retinoblastoma is the most common eye cancer of infancy and childhood; these tumours are considered to be developmental in origin. The seven cell types of the retina all derive from a pool of retinal progenitor cells (RPC). The distalless (DLX) family of evolutionarily-conserved homeobox genes encode transcription factors expressed in the developing and mature retina as well as the majority of retinoblastoma tumours examined to date. The DLX transcription factors are necessary for retinal ganglion cell (RGC) development, in part due to direct regulation of other transcription factors that are either activated or repressed during eye development. The student will undertake RNAseq and ChIPseq studies in the developing mouse retina to identify DLX2 gene regulatory networks, validate in transgenic mouse models available in the laboratory and assess expression of these DLX2 targets in retinoblastoma and/or retinal organoids. The student will also contribute to the generation of a conditional, retina-specific knockout of Dlx2 or both Dlx1/Dlx2 in the developing and/or postnatal mouse. The student will learn key methods in molecular, cell and developmental biology, including primary cell culture, 3D organoids, and advanced microscopy skills. The student should preferably have an undergraduate or advanced background in cell, developmental and/or molecular biology.