Reconstructing neuropeptide-receptor co-evolution
- Supervisors: Prof Maurice Elphick (primary) and Dr Arianna Fornili (SPCS, secondary)
- Funding: China Scholarship Council (CSC)
- Deadline: 30th January 2022
We are seeking applicants for the following PhD opportunity. The successful applicant will join a student cohort in Environment, Biodiversity and Genomics, training together, following an exciting programme designed to inspire the next generation of environmental experts, managers and leaders. They will be equipped to address some of the toughest challenges of our time.
The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 150 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.
This project will be co-supervised by Prof. Maurice Elphick and Dr. Arianna Fornili. Prof Elphick is an expert on the evolution and comparative physiology of neuropeptide signalling systems. See here for further details of Prof. Elphick's research interests and publications. Dr Fornili is an expert on computational analysis of protein dynamics and its relationship to protein function. See here for further details of Dr Fornili's research interests and publications.
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.
Specific training will provided for:
- Computational comparative analysis of genomic/transcriptomic sequence to enable identification of genes/transcripts encoding candidate neuropeptide precursor proteins and candidate neuropeptide receptors in a wide range of animal taxa.
- Computational modelling of neuropeptide receptor structures and the interactions of known or predicted neuropeptide ligands with ligand-binding sites.
Morphine exerts its powerful pain-relieving effects by mimicking the action of endogenous neuropeptides and binding to specific G-protein coupled receptors (GPCRs).
There are several hundred genes encoding GPCRs in humans and many of these are activated by neuropeptides that regulate physiologically/clinically important processes. Neuropeptide receptors have long been recognised as attractive targets for therapeutics in humans/animals and for chemicals used to control pest species. However, progress has been hindered by the lack of information on neuropeptide receptor structures. Recent advances in cryo-EM methods are providing the first insights into neuropeptide-receptor binding sites at the atomic level (e.g. Nature Chem. Biol. https://doi.org/10.1038/s41589-021-00841-3 ). Furthermore, with the development of novel AI-based protein structure prediction tools (Alphafold), there now exist exciting opportunities to investigate neuropeptide receptor structure in all animals.
This interdisciplinary PhD project will investigate for the first time the co-evolution of neuropeptide-receptor partners, informed by atomic level structural information. The project will be co-supervised by Prof. Maurice Elphick (School of Biological & Behavioural Sciences, QMUL), who is an expert on the evolution and comparative physiology of neuropeptide signalling systems, and Dr Arianna Fornili (SPCS), who is an expert on computational analysis of protein structure and dynamics. Guided by known (cryo-EM) and predicted (Alphafold) structures of human neuropeptide receptors, models of the structures of orthologous proteins in invertebrate species belonging to a variety of phyla will be generated and residues involved in binding of neuropeptide ligands will be predicted.
Template-based and integrative modelling guided by co-evolution data will be used to generate peptide-receptor complexes, which will be then refined by Molecular Dynamics simulations. This will enable reconstruction of the co-evolution of neuropeptide-receptor partners in different branches of animal phylogeny, providing a basis for applications such as developmentof novel therapuetics and/or pesticides. The project is a unique and cutting-edge interdisciplinary training opportunity for a student with BSc/MSc training in, for example, bioinformatics, biochemistry, biology, biomedical science or pharmaceutical chemistry.
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
- Be Chinese students with a strong academic background.
- Students must hold a PR Chinese passport.
- Applicants can 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 and a masters degree in an area relevant to the project. A masters degree that includes training in one or more of the following is desirable: bioinformatics/computational biology/biochemistry/molecular biology/genetics/cell biology/evolutionary biology/comparative physiology/pharmaceutical chemistry.
Applicants are required to provide evidence of their English language ability. Please see our English language requirements page for details.
The deadline for applications to Queen Mary is 30th January 2022. Applicants will need to complete an online application form by this date to be considered, including a CV, personal statement and qualifications. Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CSC scholarship (as well as any academic conditions still required to meet our entry requirements).
Once applicants have obtained their offer letter from Queen Mary they should then apply to CSC for the scholarship by the advertised deadline with the support of the project supervisor. For September 2022 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2022.
Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme.
- Tinoco AB, Barreiro-Iglesias A, Yañez Guerra LA, Delroisse J, Zhang Y, Gunner EF, Zampronio CG, Jones AM, Egertová M, Elphick MR (2021) Ancient role of sulfakinin/cholecystokinin-type signalling in inhibitory regulation of feeding processes revealed in an echinoderm. Elife. 10:e65667. doi: 10.7554/eLife.65667.
- Yañez-Guerra LA, Zhong X, Moghul I, Butts T, Zampronio CG, Jones AM, Mirabeau O, Elphick MR. (2020) Echinoderms provide missing link in the evolution of PrRP/sNPF-type neuropeptide signalling. Elife. 2020 9:e57640. doi: 10.7554/eLife.57640.
- Odekunle EA, Semmens DC, Martynyuk N, Tinoco AB, Garewal AK, Patel RR, Blowes LM, Zandawala M, Delroisse J, Slade SE, Scrivens JH, Egertová M, Elphick MR (2019) Ancient role of vasopressin/oxytocin-type neuropeptides as regulators of feeding revealed in an echinoderm. BMC Biology 17(1):60.
- Elphick MR, Mirabeau O, Larhammar D. (2018) Evolution of neuropeptide signalling systems. J Exp Biol. 221(Pt 3) doi: 10.1242/jeb.151092.
- Semmens DC, Mirabeau O, Moghul I, Pancholi MR, Wurm Y, Elphick MR (2016) Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution. Open Biology Vol 6(2) 150224 doi.org/10.1098/rsob.150224.
- Motta S, Pandini A, Fornili A, Bonati L (2021). Reconstruction of ARNT PAS-B Unfolding Pathways by Steered Molecular Dynamics and Artificial Neural Networks. J. Chem Theory Comp., DOI: 10.1021/acs.jctc.0c01308.
- Hashem S, Davies WG, Fornili A (2020). Heart Failure Drug Modifies the Intrinsic Dynamics of the Pre-Power Stroke State of Cardiac Myosin. J. Chem. Inf. Model., DOI: 10.1021/acs.jcim.0c00953
- Tiberti M, Lechner BD, Fornili A (2019). Binding Pockets in Proteins Induced by Mechanical Stress. J. Chem Theory Comp., DOI: 10.1021/acs.jctc.8b00755.
- Hashem S, Tiberti M, Fornili A (2017). Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil. PLOS Comp. Biol. DOI: 10.1371/journal.pcbi.1005826.