Reconstituting a chemosensory circuit in vitro

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project overview:
The regulated excretion of CO2 via breathing is a key life preserving that is controlled by neural circuits within the brainstem. Special cells within the brainstem measure the level of CO2 and pH of arterial and adjust the rate and depth of breathing to keep these parameters constant.

This project will seek to reconstitute the CO2-detecting circuit in vitro so that the mechanisms of signalling within the circuit, from the specialised glial cells that specifically detect CO2 to the downstream neurons that these glial cells activate and which contact the networks that control breathing, can be understood. Genetically encoded sensors for measuring cell activity will be targeted to specific components cells of the circuit and used to record and analyze signalling within this network. The student will develop existing genetically encoded sensors to optimise them to measure the concentration of ATP, a key neurotransmitter involved in this process. The measurement of specific cell activity, combined with the dynamics of released ATP, will give fundamental understanding of signalling within this network and hence the control of breathing at a whole organism level.

The interdisciplinary project will give training for the student in advanced in vivo skills, quantitative image analysis to understand signalling within neural circuits, molecular biology to design/modify new ATP sensors, mathematical modelling of ATP diffusion in neural tissue, comparison of model predictions and experimental measurements, experimental design and statistical analysis. This project will shed new light on the control of breathing and have applications in understanding human pathologies that can affect breathing.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N014294/1 01/10/2016 30/09/2025
2269009 Studentship MR/N014294/1 01/10/2019 02/01/2024 Valentin-Mihai Dospinescu