In silico modelling of endocannabinoid evolution

In the brain, the endocannabinoid (eCB) system maintains adequate neurotransmission (Lu and Mackie 2016). Indeed, the eCB system provides a negative feedback mechanism, preventing over-activation of synaptic transmission. This mechanism involves release of eCBs from the phospholipidic bilayer which, in turn, will activate specific receptors.

These receptors will then decrease neurotransmission. Such a system includes signalling molecules, such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), as well as several receptors, such as the cannabinoid receptor 1 (CB₁R), the orphan G-protein coupled receptor 55 (GPR₅₅) and the transient receptor potential of vanilloid type-1 receptor (TRPV₁).

The complex signalling (Zou and Kumar 2018) between effectors and receptors also involves enzymes responsible for the biosynthesis and metabolism of these molecules: Fatty Acid Amine Hydrolase (FAAH), N-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) and phospholipase C beta-1 (PLC-β₁).

In this project, we aim to further decipher the evolutionary origins of the eCB system, in light of what was previously observed (Elphick 2012; McPartland et al. 2006). In addition, we also aim to decipher how the eCB system can be implicated in health and disease. Indeed, several pathologies are currently under scrutiny for possible links with the eCB system (Cheung et al. 2019; Forte et al. 2020; Moreno et al. 2019), such as pain, epilepsy, neurodevelopmental disorders.

This project will involve: bioinformatics, in silico modelling and data mining. Examples of potential useful techniques can be found in the following articles: Arias-Gaguancela et al. 2023; Bian et al. 2019; Kono et al. 2013; Li et al. 2019; Wichmann and Althaus 2020; Wickert et al. 2018. Preliminary results have already been obtained in our department.

Additional Costs

There are no additional costs to this project, as this is an in silico only project. However, it is anticipated that the successful candidate invests in a high-specification computer, which will be essential to run CPU-intensive experiments.

Application Process

To begin the application process please go to: https://www.worcester.ac.uk/courses/human-biology-mphilphd and click on ‘How to Apply’ in the top menu. This PhD could be caried out on a part time or full time basis so please select the relevant application link. On the application form, please make it clear that you are applying for one of our advertised projects so we can direct it straight to the relevant people.

The Interview

All successful applicants will be offered an interview with the proposed Supervisory Team. You will be contacted by a member of the Doctoral School Team to find a suitable date. Interviews can be conducted in person or over Microsoft Teams.

Funding your PhD

For information about Doctoral Loans please visit: https://www.worc.ac.uk/study/fees-and-finance/doctoral-loans.aspx

During your PhD you can access the Research Student Support Scheme to support dissemination costs associated with your research, up to £500 a year.

Research Group

Worcester Biomedical Research Group

The Worcester Biomedical Research Group (WBRG) aims to promote multidisciplinary Biomedical Science research at the University of Worcester and fosters collaborations between staff (cross-institute), students and local health / industrial organisations.

Building sustainable societies through research into disease prevention, medical treatment and diagnostics, lies at the heart of the WBRG research ethos. We aim to achieve this goal through basic and translational Biomedical Research with particular focus on cancer, cardiovascular disease and neurodegeneration.

Widening Participation:

As part of its mission statement the University is committed to widening participation for its higher degrees. Although most candidates will have an undergraduate and/or a Masters degree, the University is happy to accept applications from candidates with relevant professional qualifications and work related experience.

Supervisory Team

Dr Mathieu Di Miceli, Dr Amy Cherry, Dr Mike Wheeler

Director of Studies

Dr Mathieu Di Miceli, Worcester Biomedical Research Group, School of Science and the Environment, University of Worcester. Dr Di Miceli has over 10 years of experience in neuroscience.

Supervisors

Dr Amy Cherry, (Protein biochemist) Worcester Biomedical Research Group, School of Science and the Environment, University of Worcester

Dr Mike Wheeler, (Expertise in Evolution and molecular biology.) Worcester Biomedical Research Group, School of Science and the Environment, University of Worcester

Research Group: Worcester Biomedical Research Group (WBRG)

For further information or an informal discussion on this project, please contact Dr Mathieu Di Micelli (Director of Studies) via email at m.dimiceli@worc.ac.uk