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(BBSRC DTP) Brain integration and processing of ingestive signals


Faculty of Biology, Medicine and Health

About the Project

After meal consumption, the brain evaluates the value of its contents and relays this information via neuronal circuits connecting the periphery with the brain (1,2). Although the brain is now recognised as the master regulator of appetite and energy homeostasis, our understanding of how and which circuits decode the post-ingestive nutritional and hedonic value of food from the periphery to the brain remain largely unknown. The advent of new genetic technologies now provide a powerful means by which to unravel the contribution of discrete neurons to appetitive behaviour and systemic energy balance with unprecedented spatial and temporal resolution (2,3).

The host laboratories have started to phenotype the neurones in the caudal brainstem, an important brain region that serves as a first relay station for peripherally generated signals entering the brain (4,5). Published (2,4) and unpublished data suggest that segregated brainstem circuits selectively respond to distinct nutritional and non-nutritional signals and transmit this information to multiple second order brain regions so that the brain can compute and attribute motivational valence. The overarching aim of this project is to resolve these circuits and characterise them at the genetic, structural and functional level.
To this end, the student will receive training in using the latest genetic technologies available that will allow him/her to genetically tag distinct brainstem neurons after they have responded to the nutritional and non-nutritional signals. This permanent genetic tagging will then allow the student to identify the neurons and their connections, record their activity during normal behaviour and selectively activate/inhibit them to interrogate their significance to behaviour.

Resolving these circuits will not only expand our understanding of how ingestive behaviour is regulated, but it will also inform design of novel medications with improved efficacy and patient compliance.

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

1. Andermann ML, Lowell BB. Toward a Wiring Diagram Understanding of Appetite Control. Neuron. 2017 Aug 16;95(4):757-778. doi: 10.1016/j.neuron.2017.06.014.

2. Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu ZW, Gao XB, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE. A Neural Circuit for Gut-Induced Reward. Cell. 2018 Oct 18;175(3):887-888. doi: 10.1016/j.cell.2018.10.018.

3. Resendez SL, Jennings JH, Ung RL, Namboodiri VM, Zhou ZC, Otis JM, Nomura H, McHenry JA, Kosyk O, Stuber GD. Visualization of cortical, subcortical and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses. Nat Protoc. 2016 Mar;11(3):566-97. doi: 10.1038/nprot.2016.021.

4. D'Agostino G, Lyons DJ, Cristiano C, Burke LK, Madara JC, Campbell JN, Garcia AP, Land BB, Lowell BB, Dileone RJ, Heisler LK. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. Elife. 2016 Mar 14;5. pii: e12225. doi: 10.7554/eLife.12225

5. Worth AA, Shoop R, Tye K, Feetham CH, D’Agostino G, Dodd GT, ….Emmerson PJ and Luckman SM. The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling. eLife 2020. 9: e55164.

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