(MRC DTP) Decoding the Brain-Immune Axis: Neuronal Circuitry and Metabolic Impact on Immune Responses
About the Project
The immune system's response is intricately linked to nutritional status, with fasting and caloric restriction reducing inflammatory damage and extreme dietary perturbations increasing susceptibility to infection and inflammatory disorders. Previous research primarily focused on nutrient availability as the key driver for dietary effects on the immune system. However, our published and unpublished data strongly indicate a critical role for the brain in this process, as interfering with distinct brain circuits responding to variations in energy availability also significantly influence inflammatory responses.
This project encompasses two main objectives. First, building upon our published and unpublished findings, the student will comprehensively characterize the structural and genetic aspects of specific metabolic-sensing brain circuits that also influence immune responses. Additionally, they will delve into the mechanisms underpinning this intricate neuro-immuno-metabolic framework in both healthy and diseased contexts. Second, leveraging this acquired knowledge, the project will explore the pathophysiological significance of normal and impaired activity within these metabolic sensing brain circuits, as well as potential strategies to target them for future therapeutic applications.
To achieve these goals, the student will receive training in cutting-edge neuroscience and immunological techniques, including genetic tools for visualizing and manipulating neuronal circuit activity in vivo (such as chemo- and optogenetics, in vivo Ca2+ imaging, and genome editing), high-throughput transcriptional and cellular immune phenotyping, and the utilization of preclinical disease models for studying metabolic and inflammatory diseases.
This project is ideal for students wishing to receive multidisciplinary training and with aspirations to build a career in the rapidly evolving field of neuroimmunology, and brain-body communication more in general. In an era marked by rapid scientific advancements and technological innovation, the intersection of neuroscience and immunology offers a compelling frontier for professional development and a fertile ground for transformative discoveries.
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form you must select MRC DTP PhD Programme. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the MRC DTP website.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application, please contact our admissions team.
Equality, Diversity and Inclusion
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.
Funding Notes
Studentship funding is for 4 years and covers tuition fees and an annual stipend. This does not include any costs associated with relocation.
References
Regulation of systemic metabolism by tissue-resident immune cell circuits. Li JH, Hepworth MR, O'Sullivan TE. Immunity. 2023 Jun 13;56(6):1168-1186.
Neuronal regulation of immunity: why, how and where? Schiller M, Ben-Shaanan TL, Rolls A. Nat Rev Immunol. 2021 Jan;21(1):20-36.
Brain control of appetite during sickness. Aviello G, Cristiano C, Luckman SM, D'Agostino G. Br J Pharmacol. 2021 May;178(10):2096-2110.
Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia. Boutagouga Boudjadja M, Culotta I, De Paula GC, Harno E, Hunter J, Cavalcanti-de-Albuquerque JP, Luckman SM, Hepworth M, White A, Aviello G, D'Agostino G. Curr Biol. 2022 Nov 7;32(21):4699-4706.e4. doi: 10.1016/j.cub.2022.09.017
Open Days
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