Transcriptional profiling of nutritional deficiency in single neurons: insights for state-dependent behaviour and healthy ageing
Award Number
BB/W007347/1Status / Stage
ActiveDates
1 July 2022 -30 June 2025
Duration (calculated)
02 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£493,358.00Funder/Grant study page
BBSRC UKRIContracted Centre
Durham UniversityPrincipal Investigator
Dr Vincent CrosetPI Contact
vincent.croset@durham.ac.ukPI ORCID
0000-0001-9696-766XWHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 692 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/W007347/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20220701 |
| End Date | 20250630 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | Durham University |
| Funding Amount | £493,358.00 |
Abstract
Brain control of state-dependent behaviour ensures appropriate nutrient intake for health, reproduction and survival. Multiple brain functions rely on a balanced diet, and deficiency of essential nutrients can drastically impair healthy ageing. The fruit fly (Drosophila melanogaster) provides an optimal platform for nutrition research. Hunger signalling is highly conserved between insects and mammals, and powerful genetic tools enable neuronal circuit dissection with unmatched accuracy. Whereas specific groups of neurons regulate feeding behaviour, a systems description of the mechanisms underlying state-dependent adaptations is lacking. How nutrient deficiency affects brain function over the life course also remains poorly understood. We will address how interactions between diet, transcription and ageing influence behaviour. Using the brain of Drosophila as a model, we will describe the effects of nutrient deficiency on transcription with single-cell resolution. This will help characterise the molecular control of food choice and consumption and explain the role of nutrition in cognitive decline. Peptidergic and dopaminergic neurons are central for regulating state-dependent behaviour. Using the latest single-cell RNA-sequencing technologies, we will reveal transcriptional correlates of nutrient deprivation across sub-populations of these neurons and provide a thorough depiction of molecular mechanisms underlying food selection. Amino acids are crucial for neurotransmission and for maintaining cognitive abilities in aged animals. We will use single-cell transcriptomics to identify how diets lacking amino acids affect the ageing brain. These experiments will establish new models to explain the interplay between nutrition, gene expression and behaviour, and open new research areas into eating disorders and healthy brain ageing.
Aims
We will use fruit flies as a model to answer two questions. First, we will determine how specific genes in the brain control food preference and consumption, depending on the most needed nutrients. Second, we will explain how the lack of amino acids affects memory and other behaviours in aged individuals