Single-cell level analysis to uncover the transcriptional logic of development and function in the Drosophila thoracic nervous system
Lead Research Organisation:
King's College London
Department Name: Developmental Neurobiology
Abstract
Drosophila is a key model for studying nervous system development and function. This project will uncover the cell-type diversity in the thoracic network using large-scale single-cell RNAseq. This approach will provide key insights into the transcriptional programs that orchestrate lineage-specific cellular modules, with particular focus on neurotransmitter and neuromodulatory systems. The project involves computational analysis of very large datasets to generate cell-type clustering and build gene networks. The 'molecular fingerprints' of these cell-types will also allow evolutionary comparisons with cells from the axial nervous systems of vertebrates and other invertebrates.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 1903523 | Studentship | BB/M009513/1 | 01/10/2017 | 30/03/2022 | Connor Sproston |
| Description | Using clonal analysis of newly generated genetic reporters we have observed evidence for the differential expression the pro-apoptotic gene (those genes that control the process of specifying cells to die), known as known as Grim, between specific groups of neurons in the developing central nervous system of the fruit fly (Drosophila melanogaster). In working towards generating expression data for each of the 4 genes within this family (Grim, Reaper, Hid and Skl) we have generated genetic GAL4 reporters for each gene with the aim of analysing the differential expression of each gene within the context of the developing CNS. Expression data from our analysis of grim has demonstrated that not only is the pro-apoptotic gene expressed in neurone that die during development, but also expressed at a low level in a number of neuron classes that do not die during development. We hypothesis that this may point towards the combinatorial expression of these 4 pro-apoptotic genes underlying the regulation of the highly specific pattern of programmed cell death observed during the development of the CNS of Drosophila melanogaster. To this end we also propose to use RNA sequencing techniques in order to validate the idea that these 4 genes may be being differentially regulated during development in order to generate the patterns of programmed cell death we observe. |
| Exploitation Route | The data collected as part of this funding will contribute to our understanding of how programmed cell death is regulated during development. The genetic reporters generated as part of this study are similarly novel and represent significant contributions to the field. |
| Sectors | Pharmaceuticals and Medical Biotechnology,Other |