Molecular changes in the function and regulation of protein synthesis during learning. Paul Donlin-Asp is a Wellcome CDA funded ESAT Fellow within the Simons Initiative for the Developing Brain (SIDB) and Institute for Neuroscience and Cardiovascular Research (INCR). He received his Ph.D. in Biochemistry, Cell, and Developmental Biology from Emory University in 2016. For his postdoctoral work, he joined Erin Schuman's lab at the Max Planck Institute for Brain Research, becoming interested in understanding how local protein synthesis is regulated during synaptic plasticity.During his postdoc, he found that pre- and postsynaptically synapses are a hotspot for local protein synthesis, which can be modulated by plasticity in a compartment-specific manner. Follow-up work demonstrated that plasticity regulates the dynamics of mRNA transport, controlling when and where specific mRNAs are associated with dendritic spines. Paul Donlin-Asp Paul's group at the University of Edinburgh aims to understand the molecular logic underlying the decision to make particular proteins at the synapse and to attempt to leverage this information to boost protein synthesis in neurodevelopment disorders resulting from genetic haploinsufficiency. Donlin-Asp Lab Website Lab members Dr. Rhys Livingstone, PhD (postdoc), Dr. Felipe Del Valle Batalla, PhD (postdoc), Oni-Glyn Wright (SIDB PhD student), Swetha Umashankar (Wellcome Trust PhD student), Lilly Green (technician), and Freya Nye (technician). Research For long-lasting changes in synaptic strength, new proteins must be synthesised. These proteins are believed to support the structural and functional modifications required for both the manifestation and maintenance of synaptic plasticity- and learning itself. To truly understand learning at a molecular level- we need to understand the function and regulation of its underlying protein synthesis.Around 5000 mRNAs can be transported to distal sites, axons and dendrites, within neurons. These mRNAs can be used to fuel localised protein synthesis at distal sites- including the synapse. Synapses however, are small, and individual mRNAs are both sparse and physically large macromolecules. We’re interested in understanding how neurons can have such diversity in what they can make and in relation to the spatial constraints of the synapse.Part of this logistical conundrum is overcome by synapses only transiently associating with individual mRNAs at any given moment, with neurons utilising active trafficking of mRNAs in dendrites and axons to allow individual mRNA molecules to be utilised by several synapses. Activity dependent capture of mRNAs allows selective proteins to be made, on demand, at the sites where these proteins are needed. However, the mechanisms underlying the capture and synthesis of mRNA into protein remains poorly understood. Main interests of the lab:What is the molecular logic underlying the synaptic capture of mRNAs and subsequent decision to translate them?What is the actual function of locally synthesized proteins at the synapse?How do complex neuronal circuits use synaptic capture of mRNA? Selected publications Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression, PNAS 2021Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments, Science 2019The survival of motor neuron protein acts as a molecular chaperone for mRNP assembly, Cell Reports 2017Full publication list (Google Scholar) This article was published on 2026-04-23
