Research projects

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The role of peripheral glial cytoplasmic mRNA localisation regulating synaptic plasticity of adjacent neurones in health and disease 

Supervisor: Ilan Davis

Project description: Synaptic plasticity is the key molecular process that regulates memory and learning. Plasticity requires mRNA localisation and translational regulation at the periphery of glial and neuronal cytoplasmic projections, where new proteins have to be synthesised rapidly in response to locale signals and electrical stimulation. We have recently uncovered numerous new localised glial mRNAs transcripts that encode many kinds of molecular processes from cytoskeletal regulation to membrane trafficking and translational regulation. Our bioinformatics analysis reveals that these localised transcripts have a high statistical association with a number of important neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. These findings suggest an exciting hypothesis that will be tested by the proposed PhD project.

Namely, that many synaptic plasticity defects associated with these devastated diseases, assumed to be neuronal in origin, may in fact originate from molecular localisation defects in glia that contact the synapses. The project will use precision genetics methods in the Drosophila larval neuromuscular junction, a well establish model system for uncovering the basic molecular mechanisms that go wrong in human neurodegenerative diseases, on account of the high degree of conservation of the underlying molecular machinery. We will interfere with gene function in specific glial subtypes or motor-neurones and compare their phenotypic outcome in relation to diseases using super resolution microscopy and single molecule imaging. Later in the PhD we will map the transacting proteins and signals required for localising the more interesting of these mRNAs and relate these molecular mechanisms to known aspects of neurodegenerative diseases.

Techniques: Molecular and cellular genetics. Advanced microscopy methods such as super-resolution and single molecule imaging. RNA biochemistry. RNA Bioinformatics. Fluorescence In Situ Hybridisation and Spatial Biology

References:

1. Lee JY, Gala DS, Kiourlappou M, Titlow JS, Teodoro RO & Davis I. (2024). Mammalian glial protrusion transcriptomes predict localization of Drosophila glial transcripts required for synaptic plasticity. Journal of Cell Biology, under revision. DOI: 10.1101/2022.11.30.518536
2. Titlow JS, et al, & Davis I. (2023). Systematic analysis of YFP traps reveals common mRNA/protein discordance in neural tissues. Journal of Cell Biology 5: 222. DOI: 10.1083/jcb.202205129
3. Titlow J, Robertson F, Järvelin A, Ish-Horowicz D, Smith C, Gratton E, Davis I. (2020). Syncrip/hnRNPQ is required for activity-induced Msp300/Nesprin expression and new synapse formation. Journal of Cell Biology, 219, 1-17. DOI: 10.1083/jcb.201903135
4. Gala DS, Titlow JS, Teodoro RO, Davis I. (2023) Far from home: the role of glial mRNA localization in synaptic plasticity. RNA 29:153-169. DOI: 10.1261/rna.079422.122

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Decoding Temporal Windows for Mitochondrial Intervention Across Species Using Data-Driven Approaches 

Supervisor: Alberto Sanz

Project description: 

Mutations in genes encoding mitochondrial OXPHOS components often cause devastating diseases. Paradoxically, lifespan can be extended in worms, flies, and mice by partially impairing mitochondrial function. Why this occurs remains poorly understood. The Sanz laboratory has revealed that the timing of mitochondrial dysfunction is critical—similar interventions produce opposing outcomes depending on when they are applied. This project aims to systematically identify conserved patterns that explain this temporal dependency.

We will analyse RNAseq and proteomics datasets from Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, and Homo sapiens, comparing short- and long-lived species. We will assess mRNA and protein expression across tissues and developmental stages, quantifying correlations between transcript and protein levels. Using machine learning, we will identify conserved expression profiles that predict lifespan outcomes.

Guided by these insights, we will use state-of-the-art genome editing in Drosophila to modulate mitochondrial function with spatiotemporal precision, targeting specific tissues and developmental windows to generate new long-lived flies.

By uncovering the timing and location rules that govern mitochondrial influence on longevity, this work will establish a foundation for future interventions to extend human healthspan.

Techniques:

• Data mining
• Transcriptomics
• Proteomics
• Statistical Analysis
• Machine Learning
• Genetics
• Molecular Biology

References:

1. Developmental mitochondrial complex I activity determines lifespan. Stefanatos R, Robertson F, Castejon-Vega B, Yu Y, Uribe AH, Myers K, Kataura T, Korolchuk VI, Maddocks ODK, Martins LM, Sanz A. EMBO Rep. 2025 Apr;26(8):1957-1983

2. NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype. Muela-Zarzuela I, Suarez-Rivero JM, Gallardo-Orihuela A, Wang C, Izawa K, de Gregorio-Procopio M, Couillin I, Ryffel B, Kitaura J, Sanz A, von Zglinicki T, Mbalaviele G, Cordero MD. Inflamm Res. 2024 Aug;73(8):1253-1266.

3. Autophagy promotes cell survival by maintaining NAD levels.
   Kataura T, Sedlackova L, Otten EG, Kumari R, Shapira D, Scialo F, Stefanatos R, Ishikawa KI, Kelly G, Seranova E, Sun C, Maetzel D, Kenneth N, Trushin S, Zhang T, Trushina E, Bascom CC, Tasseff R, Isfort RJ, Oblong JE, Miwa S, Lazarou M, Jaenisch R, Imoto M, Saiki S, Papamichos-Chronakis M, Manjithaya R, Maddocks ODK, Sanz A, Sarkar S, Korolchuk VI.
   Dev Cell. 2022 Nov 21;57(22):2584-2598.e11.

4. Mitochondrial ROS signalling requires uninterrupted electron flow and is lost during ageing in flies. Graham C, Stefanatos R, Yek AEH, Spriggs RV, Loh SHY, Uribe AH, Zhang T, Martins LM, Maddocks ODK, Scialo F, Sanz A. Geroscience. 2022 Aug;44(4):1961-1974.

5. Mitochondrial complex I derived ROS regulate stress adaptation in Drosophila melanogaster. Scialò F, Sriram A, Stefanatos R, Spriggs RV, Loh SHY, Martins LM, Sanz A.Redox Biol. 2020 May;32:101450. 

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Overview

Our staff have leading expertise and funding in human and model organism research including Drososophila melanogaster and microbes; as well as ‘omics - genomics, transcriptomics and metabolomics. They utilise a multi-disciplinary approach within the School of Molecular Biosciences with core links to Glasgow Polyomics; and have good external links with industry. Research in molecular genetics has strong alignment with the broad areas of agriculture and food security; bioscience for health; and industrial biotechnology and bioenergy.

Research topics are allied to ongoing research within the School. Projects can be related to either fundamental or translational science including clinical science and sustainable agriculture. Multi-disciplinary research approaches applied within the molecular genetics research programme include molecular genetics (human, Drosophila and microbial genetics), biochemistry, molecular biology, systems biology, ‘omics (genomics, transcriptomics, proteomics, metabolomics), bioinformatics and synthetic biology, as well as cellular imaging of biological functions using advanced technology. Specific areas of interest include:

• modelling kidney disease in Drosophila
• insect neuropeptides and GPCRs
• ‘omics and network modelling in Drosophila
• designer recombinases for genome engineering
• DNA rearrangements for Synthetic Biology
• topoisomerases and DNA topology
• mutational dynamics of unstable DNA in human disease
• new approaches to transcriptomic data analysis
• computational frameworks for omics data integration

Our PhD programme provides excellent training in cutting edge technologies that will be applicable to career prospects in both academia and industry. Many of our PhD graduates go on to research positions in academia, as well as to industry, and to policy and government organisations.

We have strong research connections with international collaborators. Funds are available through the College of Medical, Veterinary and Life Sciences to allow visits to international laboratories where part of your project can be carried out. This provides an excellent opportunity for networking and increasing the scientific knowledge and skill set of our PhD students.

Study options

PhD

• Duration: 3/4 years full-time; 5 years part-time

Individual research projects are tailored around the expertise of principal investigators.

MSc (Research)

• Duration: 1 year full-time; 2 years part-time