"Decoding individual biological molecules and their interplay at subcellular locations greatly extends our understanding of the physiological and pathogenic mechanisms underlying a broad range of neuronal behaviours." Julie Qiaojin Lin
UK DRI Emerging Leader
Dr Julie Qiaojin Lin is a Sir Henry Wellcome Postdoctoral Fellow hosted by Prof Jernej Ule (UK DRI at King's), Prof Clemens Kaminski (Affiliated Researcher, UK DRI at Cambridge) and Prof Giovanna Mallucci (Altos Labs). Dr Lin joined the UK DRI in 2018 following her PhD training in Prof Christine Holt’s Lab at Cambridge as a Gates Cambridge Scholar, studying local protein synthesis in axons of healthy and disease-affected neurons. Becoming a UK DRI Emerging Leader in 2021, her current research programme focuses on the thermoregulation of RNA metabolism and RNA-binding proteins in neuronal compartments and how the localised molecules orchestrate synaptic structural and functional plasticity at distinct temperatures. Using advanced imaging and multi-omics approaches, Dr Lin investigates early aberrant changes of temperature-dependent local molecular organisation that ultimately lead to synapse loss and neurodegeneration.
1. At a glance
Our brain temperatures oscillate through the day according to circadian rhythm and vary between brain areas and individuals of different age, sex and progression of dementia. Such temperature variation has a large impact on how RNA and proteins behave in neurons and other brain cells. Encouragingly, lowering the body or brain temperatures to 32°C to 35°C for a short period protects injured or dementia-affected neurons and prolongs their survival. Dr. Lin’s research explores how neuronal molecules, especially those at distal ends of neuronal extensions, work together to respond to transient temperature drops in healthy and diseased brains.
2. Scientific goals
Local protein synthesis in distal neuronal compartments, relying on localised mRNA and dynamically assembled translation machinery at the vicinity, enables synapses to autonomously and rapidly remodel their proteomes in response to local stimuli, including temperature fluctuations and pathogenic insults. Dr Lin’s team investigates how mild hypothermia, shown to be neuroprotective in dementia models, influences RNA-binding protein functions, RNA splicing, global and local mRNA translation, providing insights into temperature- and RNA-based therapeutic strategies.
Main objectives and research goals:
- Understand how hypothermia alters the activity and functions of RNA-binding proteins and different steps of RNA metabolism.
- Uncover the molecular and neuronal functions of a neuroprotective cold-inducible RNA-binding protein, RBM3.
- Investigate the impact of hypothermia on synaptic mRNA localisation and local synthesis of proteins key to synaptic health and survival.
Within UK DRI
- Prof Jernej Ule, UK DRI at King's
- Dr Marc-David Ruepp, UK DRI at King's
- Prof Clemens Kaminski, Affiliated Researcher, UK DRI at Cambridge
Beyond UK DRI:
- Prof Giovanna Mallucci, Altos Labs
- Dr Emmanouil Metzakoipian, Bit Bio
- Prof Christine Holt, University of Cambridge
- Prof Peter St George-Hyslop, University of Cambridge
- Dr. Nicholas Clifton, University of Exeter
neuroprotection, synapse maintenance, cold shock response, RNA-binding proteins, RNA splicing, RNA localisation, local protein synthesis, biomolecular condensates
iPSC-derived neuron cultures, compartmentalised neuron cultures, RNA-Seq, CLIP, proteomics, CRISPR/Cas9 screening, fluorescent live imaging, calcium imaging
6. Key publications
Lin, J. Q.*, van Tartwijk, F. W.*, & Holt, C. E. (2021). Axonal mRNA translation in neurological disorders. RNA biology, 18(7), 936-961.
Cioni, J. M.*, Lin, J. Q.*, Holtermann, A. V., Koppers, M., Jakobs, M. A., Azizi, A., ... & Holt, C. E. (2019). Late endosomes act as mRNA translation platforms and sustain mitochondria in axons. Cell, 176(1-2), 56-72.
Qamar, S.*, Wang, G.*, Randle, S. J.*, Ruggeri, F. S.*, Varela, J. A.*, Lin, J. Q.*, Phillips, E. C. *, ... & St George-Hyslop, P. (2018). FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-π interactions. Cell, 173(3), 720-734.
Murakami, T.*, Qamar, S.*, Lin, J. Q.*, Schierle, G. S. K.*, Rees, E., Miyashita, A., ... & St George-Hyslop, P. (2015). ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function. Neuron, 88(4), 678-690.