Skip to main content
School of Biological and Behavioural Sciences

Neuronal control of food intake and stress response on neurodegeneration (ND) using zebrafish as a model

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.

The lab consists of 5 PhD students and 2 PDRAs. Laboratory space is equipped with all necessay equipment ilncuding high resolution micorsocpes and molecular biology facilities. We have a newly refurbished zebrafish facility with dedicated behavioural rooms and imaging facilities.

Training and development

Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.

The successful student will be trained in application of machine learning to drug discovery and in the use of in vitro and in vivo cell biological and behavioural studies to assess effects of hemp and hemp derivatives in medically related outcomes.

Project description

The melanocortin system plays a critical role in avariety of physiological systems [1]. The melanocortin peptides derived from the cleavage of pro-opiomelanocortin precursor protein (POMC) act on five G protein coupled receptors, named Melanocortin receptors type 1 -type 5 (MC1R-MC5R). There is a direct link with obesity and neurodegenerationD. Population studies on neurodegeneration (ND) have shown that mid-life obesity (BMI>30; 40-65 yrs old) increases dementia risk while later life obesity (>65 yrs old) decreases dementia risk [2].

The melanocortin (MC) system has a key role in food intake and metabolism. Mutations in melanocortin-4- receptor (MC4R) are the most common cause of monogenic obesity in humans [3]. MCs, ligands for MC4R, have been shown to protect against ND. The effect of MC4R deficiency on ND is less well known. Moreover, studies have shown that weight loss precedes dementia onset and patients with dementia lose appetite.

This points to disruption of neuronal feeding circuits prior to dementia onset, in keeping with our preliminary data. In humans, mutations in the MC2R give rise to familial glucocorticoid deficiency [5]. Dysregulation of the hypothalamic pituitary adrenal axis is seen in obesity [6]. We hypothesise that feeding and stress dysregulation directly affects cognition and perturbation of the MC system will alter cognitive outcomes and age-related cognitive decline.

The project examines food behaviour/response to stress and the MC system in zebrafish ND models and the effect of MC4R deficiency on cognition, focusing on working memory as a key indicator of age-related cognitive decline. This study will provide mechanistic insights into appetite regulation in ND and the effects of MC4R deficiency on cognition and cognitive decline.

The overarching aim of the project is to explore the relationship between neuronal control of appetite, stress and ND. The specific aims are: (1) Assessment of ND zebrafish lines [7] at early and late time points (2) Determination of the effects of fasting and stress on working memory in ND zebrafish and WT fish (3) Study of working memory in MC4R deficient zebrafish at early and late stages (4) Modelling of the impact of MC4R deficiency in ND zebrafish (by crossing MC4R-/- zebrafish which is in house with ND zebrafish).

With each specific aim, we will study groups of zebrafish at larva stage, 3, 9 and 18 months and assess (a) food intake (b) working memory (c) CNS and hypothalamic morphology and microarchitecture (f) function of MC system (g) effects of stress.

Funding

This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.

Eligibility and applying

Applicants must be:
- Chinese students with a strong academic background.
- Students holding a PR Chinese passport.
- Either be resident in China at the time of application or studying overseas.
- Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.

Please refer to the CSC website for full details on eligibility and conditions on the scholarship. 

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in an area relevant to the project (biology, pharmacology, neuroscience, genetics, biomedical science). A masters degree is desirable, but not essential.

Informal enquiries about the project can be sent to Caroline Brennan at c.h.brennan@qmul.ac.uk.

Formal applications must be submitted through our online form by 31st January 2024 for consideration, including a CV, personal statement and qualifications. You must meet the IELTS/ English Language requirements for your course and submit all required documentation (including evidence of English Language) by 14th March 2024. You are therefore strongly advised to sit an approved English Language test as soon as possible. 

Shortlisted applicants will be invited for a formal interview by the supervisor. If you are successful in your application, then you will be issued an QMUL Offer Letter, conditional on securing a CSC scholarship along with academic conditions still required to meet our entry requirements. Once applicants have obtained their QMUL Offer Letter, they should then apply to CSC for the scholarship by in March 2024 with the support of the supervisor.

Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme. For further information, please go to: https://www.qmul.ac.uk/scholarships/items/china-scholarship-council-scholarships.html 

Apply Online

References

  1. Novoselova, T. V., Chan, L. F., and Clark, A. J. L. (2018) Pathophysiology of melanocortin receptors and their accessory proteins. Best Pract Res Clin Endocrinol Metab 32, 93-106
  2. Mazon, J. N., de Mello, A. H., Ferreira, G. K., and Rezin, G. T. (2017) The impact of obesity on neurodegenerative diseases. Life Sci 182, 22-28
  3. Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., and O'Rahilly, S. (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20, 111-112
  4. Baiamonte, M., Brennan, C. H., and Vinson, G. P. (2015) Sustained action of developmental ethanol exposure on the cortisol response to stress in zebrafish larvae and adults. PLoS One 10, e0124488
  5. Novoselova, T., King, P., Guasti, L., Metherell, L. A., Clark, A. J. L., and Chan, L. F. (2019) ACTH signalling and adrenal development: lessons from mouse models. Endocr Connect
  6. Bose, M., Olivan, B., and Laferrere, B. (2009) Stress and obesity: the role of the hypothalamic-pituitary-adrenal axis in metabolic disease. Curr Opin Endocrinol Diabetes Obes 16, 340-346
  7. Hin, N., Newman, M., Kaslin, J., Douek, A. M., Lumsden, A., Nik, S. H. M., Dong, Y., Zhou, X. F., Manucat-Tan, N. B., Ludington, A., Adelson, D. L., Pederson, S., and Lardelli, M. (2020) Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2. PLoS One 15, e0227258
  8. Cleal, M., Fontana, B. D., Ranson, D. C., McBride, S. D., Swinny, J. D., Redhead, E. S., and Parker, M. O. (2020) The Free-movement pattern Ymaze: A cross-species measure of working memory and executive function. Behav Res Methods
  9. Evans, J. R., Torres-Perez, J. V., Miletto Petrazzini, M. E., Riley, R., and Brennan, C. H. (2021) Stress reactivity elicits a tissue-specific reduction in telomere length in aging zebrafish (Danio rerio). Sci Rep 11, 33
Back to top