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Mapping the 3D structure of the gut to investigate inter-organ signalling in humans and flies


Project Description

The gut has a complex 3D structure, forming a looping folded path inside the abdomen. Although the function of looping was primarily thought to allow the long gut tube to fit inside the body, recent work in flies has suggested that the position of specific gut loops relative to other organs has important consequences for signalling. In the male fruit fly, male-specific carbohydrate metabolism in the intestine is extrinsically controlled by the neighbouring male gonad (1). Physical proximity seems to be important for this signalling as the relevant gut loop comes into close physical contact with the tip of the male gonad from where the signalling molecule, citrate, is released. This work opens up the possibility that gut-organ proximity is a generalizable signalling mechanism used in other contexts. We want to explore the possibility of gut physical communication with other neighbouring organs and between neighbouring gut loops. We also now want to extend this work to investigate the role of gut-organ proximity-based signalling in humans.

The project will make use of both the fruit fly Drosophila melanogaster and humans to quantitatively analyse the 3D shape of the intestine in the context of the neighbouring organs. This will involve (i) using intravital imaging techniques to capture 3D reconstructions of the human and fly gut and (ii) developing machine learning computer vision techniques for dynamic analysis of function (2) to explore the relationship of the gut to other organs. The project with make use of a diverse array of approaches to merge wet-lab biology and clinical imaging with computational image processing and analysis using state-of-the-art machine learning methodologies.

Lab homepages:
https://lms.mrc.ac.uk/research-group/gut-signalling-and-metabolism/
https://lms.mrc.ac.uk/research-group/computational-cardiac-imaging/

To Apply: Please visit our website (https://lms.mrc.ac.uk/study-here/phd-studentships/lms-3-5yr-studentships/) to download an application form.

Funding Notes

This project is one of multiple available projects potentially funded by the MRC. If successful the studentship would cover all tuition fee payments and includes a tax-free stipend amounting to £21,000pa (paid in monthly installments directly to the student) for 3.5 years.

Whilst this funding is available to students worldwide, due to the higher tuition fee rate of overseas students competition is higher and so only exceptional OS applicants will be considered.

References

Hudry B, de Goeij E, Mineo A, Gaspar P, Hadjieconomou D, Studd C, Mokochinski JB, Kramer HB, Plaçais PY, Preat T and Miguel-Aliaga I. (2019). Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation. Cell. 178, 901-918.

Bello GA, Dawes TJW, Duan J, Biffi C, de Marvao A, Howard L, Gibbs JSR, Wilkins MR, Cook SA, Rueckert D and O'Regan DP. (2019) Deep learning cardiac motion analysis for human survival prediction. Nat Mach Intell. 1, 95-104.

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