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(BBSRC DTP CASE) Impact of Dietary Modification on the Adaptive Immune System in Health and Disease


Faculty of Biology, Medicine and Health

About the Project

ndividuals age chronologically but also biologically at a different pace throughout life. Among many hallmarks of aging, the gradual functional decline of the immune system (IS) called immunosenescence is associated with increased inability to fight infections while putting elderlies at increasing risks of cancers and chronic inflammatory diseases. A major feature of the aged IS are the gradual deterioration in the production of B and T cells, diminished effector responses and the emergence of senescent memory cells with impaired functional capacity. The mechanisms underlying immune senescence remain poorly defined, but include host genetics as well as environmental factors and lifestyle such as diet. Increasing amount of evidence suggest a beneficial impact of nutritional interventions in the ability of elderlies to mount effective immune responses and respond to vaccines. Metabolic activities are critical for T cell functions, proliferation, survival, memory formation and recall responses. During viral infection, intrinsic regulation of metabolic processes and nutrient sensing help ensure that adequate energy is available to support clonal expansion and effector functions. These processes are targeted by cancer cells depleting the microenvironment of nutrients thus detrimentally altering metabolic changes necessary for the generation of effective T cell responses. Notably the amino acid L-arginine has been shown to be key in T-cell metabolism’s regulation, fitness and survival and is instrumental in promoting the generation of antigen-specific T cells with enhanced effector activity. Another consequence of aging, the vulnerability of elderlies to malnutrition and associated weight loss pose even greater challenges as it puts them at greater risks of their immune system being further weakened. Given the prominent role of T cells in controlling both infectious pathogens and disease, dietary modification may provide a mechanism to reverse the decline in immune cell function with age and restore adaptive responses. Such dietary intervention is the focus of nutritional companies in various clinical settings and is explored in broad applications across a range of age-related pathologies.

Using various models across the aging process, we will explore the impact of dietary restriction or supplementation on the IS with an emphasis on the adaptive immune cell populations. In order to determine whether nutritional modification can influence and boost immune responses in the disease setting, the efficacy of anti-cancer immune responses will be explored in murine tumour models in ageing. Together, these data will provide biological insight in to the potential for dietary modification to help combat age related immune senescence.

https://www.research.manchester.ac.uk/portal/paul.townsend.html
https://www.research.manchester.ac.uk/portal/jamie.honeychurch.html
https://www.research.manchester.ac.uk/portal/clare.mills.html
https://www.waters.com/nextgen/gb/en.html

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 Primary 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

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 https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Funding Notes

This is a CASE studentship in partnership with Waters Corporation. 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.

References

1. Aiello, A. et al., Front. Immunol., 25 September 2019 | https://doi.org/10.3389/fimmu.2019.02247
2. Maijo, M. et al., Mechanisms of Ageing and Development, 2014, Volumes 136–137, Pages 116-128 | https://doi.org/10.1016/j.mad.2013.12.003
3. Geiger, R. et al., Cell, 2016, 167, 829-842 |https://doi.org/10.1016/j.cell.2016.09.031
4. Munford, H. et al., Front. Mol. Biosci., 25 October 2019 | https://doi.org/10.3389/fmolb.2019.00118
5. Larbi, A. Cexus, O. Bosco, N., Nutrition as a Tool to Reverse Immunosenescence? 2018, Chapter 26, Pages 319-337 ׀https://doi.org/10.1016/B978-0-12-805417-8.00026-3

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